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    Clinical Trial Results:
    A Phase 2, Multicenter, Randomized Open-Label Study to Determine the Efficacy of Lenalidomide (Revlimid®) Versus Investigators Choice in Patients With Relapsed or Refractory Mantle Cell Lymphoma

    Summary
    EudraCT number
    		 2008-003389-25
    Trial protocol
    		 BE   GB   CZ   DE   ES   FR   IT   DK   SE   GR  
    Global end of trial date
    09 Oct 2018

    Results information
    Results version number
    		 v1(current)
    This version publication date
    18 Oct 2019
    First version publication date
    18 Oct 2019
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CC-5013-MCL-002
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00875667
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Celgene Corporation
    Sponsor organisation address
    86 Morris Avenue, Summit, United States, 07901
    Public contact
    Clinical Trial Disclosure, Celgene Corporation, 01 888-260-1599, ClinicalTrialDisclosure@Celgene.com
    Scientific contact
    Jeffrey Jones, MD, Celgene Corporation, 01 908-673-9686, JeJones@celgene.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    18 Oct 2018
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    09 Oct 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To compare the progression free survival (PFS) of lenalidomide monotherapy versus investigators choice single agent in patients with mantle cell lymphoma (MCL) who are refractory to their regimen or have relapsed once, twice or three times.
    Protection of trial subjects
    Archiving of Essential Documents, Personal Data Protection, Informed Consent
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    26 May 2009
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety, Efficacy
    Long term follow-up duration
    		 5 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 5
    Country: Number of subjects enrolled
    Sweden: 3
    Country: Number of subjects enrolled
    United Kingdom: 25
    Country: Number of subjects enrolled
    Belgium: 5
    Country: Number of subjects enrolled
    Czech Republic: 32
    Country: Number of subjects enrolled
    France: 38
    Country: Number of subjects enrolled
    Germany: 19
    Country: Number of subjects enrolled
    Israel: 2
    Country: Number of subjects enrolled
    Italy: 25
    Country: Number of subjects enrolled
    Netherlands: 1
    Country: Number of subjects enrolled
    Poland: 45
    Country: Number of subjects enrolled
    Russian Federation: 54
    Worldwide total number of subjects
    254
    EEA total number of subjects
    198
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    82
    From 65 to 84 years
    169
    85 years and over
    3

    Subject disposition

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    Recruitment
    Recruitment details
    		 The study was conducted at 67 sites including 3 sites in Belgium, 3 in Czech Republic, 14 in France, 7 in Germany, 2 in Israel, 10 in Italy, 1 in the Netherlands, 5 in Poland, 11 in Russia, 4 in Spain, 2 in Sweden, and 5 in the United Kingdom (UK).

    Pre-assignment
    Screening details
    		 Participants were randomized in a 2:1 ratio to receive lenalidomide monotherapy or investigators choice. Participants were stratified according to the time since diagnosis (< 3 years or ≥ 3 years), time since last treatment (< 6 months [refractory] or ≥ 6 months) and if they had undergone a prior stem cell transplant or not.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Lenalidomide
    Arm description
    		 Participants received lenalidomide (LEN) 25 mg capsules orally every day for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity. Participants with moderate renal insufficiency (creatinine clearance is ≥ 30 mL/min but < 60mL/min received 10 mg lenalidomide for 21 days of each 28-day cycle (Cycles 1 and 2). After Cycle 2, if the participant remained free of Grade 3 or Grade 4 toxicity, the dose was increased to 15 mg lenalidomide for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity.
    Arm type
    		 Experimental

    Investigational medicinal product name
    CC-5013
    Investigational medicinal product code
    Other name
    Revlimid
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Lenalidomide 25 mg capsules PO QD for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity.

    Arm title
    		 Investigators Choice
    Arm description
    		 Participants received a single agent investigators choice (IC) of chlorambucil 40 mg/m^2 PO every 28 days until progressive disease (PD) or toxicity, OR rituximab 375 mg/m^2 by intravenous (IV) infusion on days 1, 8, 15 and 22 of each 56-day treatment cycle until PD or toxicity, OR cytarabine 1-2 g/m^2 by IV infusion on days 1 and 2 of each 28 day treatment cycle; up to 6 cycles, OR gemcitabine 1000 mg/m^2 by IV infusion on days 1, 8 and 15 of each 28 day treatment cycle; up to 6 cycles OR oral fludarabine 40 mg/m^2 or IV fludarabine 25 mg/m^2 on days 1 through 5 of each 28-day cycle; up to 6 cycles. Participants were given the option to enter into the lenalidomide crossover phase if PD occurred and received lenalidomide 25 mg capsules daily on days 1 to 21 of each 28 day treatment cycle until PD or toxicity.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Chlorambucil
    Investigational medicinal product code
    Other name
    Leukeran
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Chlorambucil 40 mg/m^2 PO every 28 days until progressive disease (PD) or toxicity.

    Investigational medicinal product name
    Rituximab
    Investigational medicinal product code
    Other name
    Rituxan, MabThera
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Rituximab 375 mg/m^2 by intravenous (IV) infusion on days 1, 8, 15 and 22 of each 56-day treatment cycle until PD or toxicity

    Investigational medicinal product name
    Cytarabine
    Investigational medicinal product code
    Other name
    Cytosar-U®; Ara-C, Arabinosylcytosine
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Cytarabine 1-2 g/m^2 by IV infusion on days 1 and 2 of each 28 day treatment cycle; up to 6 cycles.

    Investigational medicinal product name
    Gemcitabine
    Investigational medicinal product code
    Other name
    Gemzar
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Gemcitabine 1000 mg/m^2 by IV infusion on days 1, 8 and 15 of each 28 day treatment cycle; up to 6 cycles.

    Investigational medicinal product name
    Fludarabine
    Investigational medicinal product code
    Other name
    Fludara®
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Fludarabine 25 mg/m^2 by IV infusion on days 1 through 5 of each 28-day cycle; up to 6 cycles.

    Investigational medicinal product name
    Fludarabine
    Investigational medicinal product code
    Other name
    Fludarabine phosphate
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Fludarabine 40 mg/m^2 by mouth on days 1 through 5 of each 28-day cycle; up to 6 cycles.

    Number of subjects in period 1
    		Lenalidomide Investigators Choice
    Started
    170
    84
    Crossover from IC to Lenalidomide
    0
    40
    Participants Treated
    167
    83
    Completed
    0
    11
    Not completed
    170
    73
         Adverse event, serious fatal
    7
    2
         Consent withdrawn by subject
    17
    5
         Adverse event, non-fatal
    29
    10
         Miscellaneous
    12
    6
         Disease Progression
    100
    49
         Randomized but no Study Drug Given
    3
    1
         Protocol deviation
    2
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Lenalidomide
    Reporting group description
    		 Participants received lenalidomide (LEN) 25 mg capsules orally every day for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity. Participants with moderate renal insufficiency (creatinine clearance is ≥ 30 mL/min but < 60mL/min received 10 mg lenalidomide for 21 days of each 28-day cycle (Cycles 1 and 2). After Cycle 2, if the participant remained free of Grade 3 or Grade 4 toxicity, the dose was increased to 15 mg lenalidomide for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity.

    Reporting group title
    Investigators Choice
    Reporting group description
    		 Participants received a single agent investigators choice (IC) of chlorambucil 40 mg/m^2 PO every 28 days until progressive disease (PD) or toxicity, OR rituximab 375 mg/m^2 by intravenous (IV) infusion on days 1, 8, 15 and 22 of each 56-day treatment cycle until PD or toxicity, OR cytarabine 1-2 g/m^2 by IV infusion on days 1 and 2 of each 28 day treatment cycle; up to 6 cycles, OR gemcitabine 1000 mg/m^2 by IV infusion on days 1, 8 and 15 of each 28 day treatment cycle; up to 6 cycles OR oral fludarabine 40 mg/m^2 or IV fludarabine 25 mg/m^2 on days 1 through 5 of each 28-day cycle; up to 6 cycles. Participants were given the option to enter into the lenalidomide crossover phase if PD occurred and received lenalidomide 25 mg capsules daily on days 1 to 21 of each 28 day treatment cycle until PD or toxicity.

    Reporting group values
    		 Lenalidomide Investigators Choice Total
    Number of subjects
    		 170 84 254
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 55 27 82
        From 65-84 years
    		 113 56 169
        85 years and over
    		 2 1 3
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 68.0 ( 9.38 ) 67.5 ( 8.20 ) -
    Sex: Female, Male
    Units: Subjects
        Female
    		 47 21 68
        Male
    		 123 63 186
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0
        Asian
    		 0 0 0
        Native Hawaiian or Other Pacific Islander
    		 0 0 0
        Black or African American
    		 0 0 0
        White
    		 161 80 241
        More than one race
    		 0 0 0
        Unknown or Not Reported
    		 9 4 13
    Eastern Cooperative Oncology Group (ECOG) Performance Status
    ECOG performance status is used by doctors and researchers to assess how a subject's disease is progressing, assess how the disease affects the daily living activities of the subject and determine appropriate treatment and prognosis. 0 = Fully Active, able to carry on all pre-disease performance without restriction; 1 = Restricted in physically strenuous activity but ambulatory and able to carry out light work; 2 = Ambulatory and capable of all self-care but unable to carry out any work activities; 3 = Capable of only limited self-care; 4 = Completely Disabled, No self-care
    Units: Subjects
        0 = Fully Active
    		 65 36 101
        1 = Restrictive but Ambulatory
    		 77 37 114
        2 = Ambulatory but Unable to Work
    		 27 11 38
        3 = Limited Self-Care
    		 0 0 0
        Missing
    		 1 0 1
    Stage of Mantle Cell Lymphoma (MCL) at Diagnosis
    Ann Arbor staging is the staging system for lymphomas, both in Hodgkin's lymphoma (previously called Hodgkin's disease) and Non-Hodgkin lymphoma (abbreviated NHL). Stage I = Involvement of 1 Lymph Node (LN) or extralymphatic region Stage II = ≥ 2 LN sites on the same side of the diaphragm Stage III = LN regions on both sides of the diaphragm; may include spleen and 1 extralymphatic organ Stage IV = involvement of ≥ 1 extralymphatic organs with or without associated LN involvement (diffuse or disseminated)
    Units: Subjects
        Stage I
    		 3 2 5
        Stage II
    		 10 1 11
        Stage III
    		 30 20 50
        Stage IV
    		 123 59 182
        Missing
    		 4 2 6
    MCL International Prognostic Index (MIPI) Score at Baseline
    A prognostic index predictive of the outcome in advanced mantle cell lymphoma
    Units: Subjects
        Low Risk
    		 42 21 63
        Intermediate Risk
    		 66 37 103
        High Risk
    		 60 25 85
        Missing
    		 2 1 3
    Bone Marrow Involvment as Baseline
    Bone marrow involvement (biopsy score) was categorized according to the following observations (Cheson, 1999): (i) positive, if unequivocal cytologic or architectural evidence of malignancy, (ii) negative, if no aggregates or only a few well-circumscribed lymphoid aggregates, or (iii) indeterminate, if increased number or size of aggregates without cytologic or architectural atypia
    Units: Subjects
        Negative
    		 27 11 38
        Intermediate
    		 4 3 7
        Positive
    		 21 13 34
        Missing
    		 118 57 175

    End points

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    End points reporting groups
    Reporting group title
    Lenalidomide
    Reporting group description
    		 Participants received lenalidomide (LEN) 25 mg capsules orally every day for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity. Participants with moderate renal insufficiency (creatinine clearance is ≥ 30 mL/min but < 60mL/min received 10 mg lenalidomide for 21 days of each 28-day cycle (Cycles 1 and 2). After Cycle 2, if the participant remained free of Grade 3 or Grade 4 toxicity, the dose was increased to 15 mg lenalidomide for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity.

    Reporting group title
    Investigators Choice
    Reporting group description
    		 Participants received a single agent investigators choice (IC) of chlorambucil 40 mg/m^2 PO every 28 days until progressive disease (PD) or toxicity, OR rituximab 375 mg/m^2 by intravenous (IV) infusion on days 1, 8, 15 and 22 of each 56-day treatment cycle until PD or toxicity, OR cytarabine 1-2 g/m^2 by IV infusion on days 1 and 2 of each 28 day treatment cycle; up to 6 cycles, OR gemcitabine 1000 mg/m^2 by IV infusion on days 1, 8 and 15 of each 28 day treatment cycle; up to 6 cycles OR oral fludarabine 40 mg/m^2 or IV fludarabine 25 mg/m^2 on days 1 through 5 of each 28-day cycle; up to 6 cycles. Participants were given the option to enter into the lenalidomide crossover phase if PD occurred and received lenalidomide 25 mg capsules daily on days 1 to 21 of each 28 day treatment cycle until PD or toxicity.

    Primary: Kaplan Meier Estimate for Progression Free Survival (PFS) by Independent Review Committee (IRC) Central Review

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    End point title
    		 Kaplan Meier Estimate for Progression Free Survival (PFS) by Independent Review Committee (IRC) Central Review
    End point description
    PFS was defined as time of randomization to the first observation of disease progression or death due to any cause, whichever was first. If a participant had not progressed or died, PFS was censored at the time of last assessment when the participant was known not to have progressed. For participants who received other anti-lymphoma therapy with no evidence of progression, PFS was censored at time of last tumor assessment with no evidence of progression prior to the start of new anti-lymphoma treatment. Intent to Treat (ITT) population included all randomized participants.
    End point type
    Primary
    End point timeframe
    From randomization to progression of disease or death; up to data cut off date of 07 March 2014; overall median follow-up time was 93.9 weeks
    End point values
    		 Lenalidomide Investigators Choice
    Number of subjects analysed
    170
    84
    Units: weeks
        median (confidence interval 95%)
    37.6 (24.0 to 52.6)
    22.7 (15.9 to 30.1)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Lenalidomide v Investigators Choice
    Number of subjects included in analysis
    254
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.012 [1]
    Method
    		 Stratified Log Rank Test
    Parameter type
    		 Stratified Hazard Ratio
    Point estimate
    0.63
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.43
         upper limit
    		 0.9
    Notes
    [1] - Stratification factors were: time from diagnosis to first dose, time from last prior anti-lymphoma therapy to first dose, prior stem cell transplant, and MIPI at baseline

    Primary: Kaplan Meier Estimate for Progression Free Survival by Investigators Assessment at the Final Analysis

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    End point title
    		 Kaplan Meier Estimate for Progression Free Survival by Investigators Assessment at the Final Analysis
    End point description
    Kaplan Meier estimates of PFS were defined as the time from randomization to the first observation of disease progression or death due to any cause, whichever was first. If a participant had not progressed or died, PFS was censored at the time of last completed assessment when the participant was known not to have progressed. For participants who received other anti-lymphoma therapy with no evidence of progression, PFS was censored at time of last tumor assessment with no evidence of progression prior to the start of new anti-lymphoma treatment. ITT population included all randomized participants.
    End point type
    Primary
    End point timeframe
    From randomization to progression of disease or death; up to study discontinuation of 09 October 2018; overall median follow-up time was 285 weeks
    End point values
    		 Lenalidomide Investigators Choice
    Number of subjects analysed
    170
    84
    Units: weeks
        median (confidence interval 95%)
    37.3 (24.1 to 52.6)
    23.6 (15.9 to 33.3)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Lenalidomide v Investigators Choice
    Number of subjects included in analysis
    254
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.003 [2]
    Method
    		 Stratified Log Rank Test
    Parameter type
    		 Stratified Hazard Ratio
    Point estimate
    0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.43
         upper limit
    		 0.85
    Notes
    [2] - Stratification factors were: time from diagnosis to first dose, time from last prior anti-lymphoma therapy to first dose, prior stem cell transplant, and MIPI at baseline

    Secondary: Percentage of Participants Who Achieved an Overall Response According to the IRC Central Review

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    End point title
    		 Percentage of Participants Who Achieved an Overall Response According to the IRC Central Review
    End point description
    Overall Response Rate (ORR) was defined as the percentage of participants whose best response was Complete Response (CR), Complete Response unconfirmed (CRu) or Partial Response (PR). Participants who discontinued before any response had been observed or changed to other anti-lymphoma treatments before response had been observed, were considered as non-responders. Tumor Response was assessed by a modification of the International Lymphoma Workshop Response Criteria, IWRC, Cheson, 1999; CR is defined as the disappearance of all clinical and radiographic evidence of disease; CRu is defined as a CR, with a 1) residual lymph node mass >1.5 cm that has decreased by 75% in the sum of the product of the diameters (SPD). Individual nodes previously confluent decreased by more than 75% in the SPD compared with original mass; 2) indeterminate bone marrow; PR = is defined ≥50% decrease in 6 largest nodes or nodal masses. ITT population included all randomized participants.
    End point type
    Secondary
    End point timeframe
    From date of randomization to the data cut-off date of 07 March 2014; median treatment duration was 24.3 weeks for the lenalidomide arm and 13.1 weeks for the investigators choice arm
    End point values
    		 Lenalidomide Investigators Choice
    Number of subjects analysed
    170
    84
    Units: Percentage of Participants
        number (confidence interval 95%)
    40.0 (32.58 to 47.78)
    10.7 (5.02 to 19.37)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Lenalidomide v Investigators Choice
    Number of subjects included in analysis
    254
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Chi-squared
    Confidence interval

    Secondary: Percentage of Participants Who Achieved an Overall Response as Assessed by the Investigator at the Final Analysis

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    End point title
    		 Percentage of Participants Who Achieved an Overall Response as Assessed by the Investigator at the Final Analysis
    End point description
    Overall Response Rate (ORR) was defined as the percentage of participants whose best response was Complete Response, Complete Response unconfirmed or Partial Response. Participants who had discontinued before any response has been observed or changed to other anti-lymphoma treatments before response had been observed, were considered as non-responders. Tumor Response was assessed by a modification of the International Lymphoma Workshop Response Criteria, IWRC, Cheson, 1999; CR is defined as the disappearance of all clinical and radiographic evidence of disease; CRu is defined as a CR, with a 1) residual lymph node mass >1.5 cm that has decreased by 75% in the sum of the product of the diameters (SPD). Individual nodes previously confluent decreased by more than 75% in the SPD compared with original mass; 2) indeterminate bone marrow; PR = is defined ≥50% decrease in 6 largest nodes or nodal masses. ITT population included all randomized participants.
    End point type
    Secondary
    End point timeframe
    From date of randomization to the study discontinuation date of 09 October 2018; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm
    End point values
    		 Lenalidomide Investigators Choice
    Number of subjects analysed
    170
    84
    Units: Percentage of Participants
        number (confidence interval 95%)
    45.9 (38.23 to 53.68)
    22.6 (14.20 to 33.05)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Lenalidomide v Investigators Choice
    Number of subjects included in analysis
    254
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Chi-squared
    Confidence interval

    Secondary: Kaplan Meier Estimate for Duration of Response (DOR) According to the IRC Central Review

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    End point title
    		 Kaplan Meier Estimate for Duration of Response (DOR) According to the IRC Central Review
    End point description
    Duration of response was defined as the time from when the first response of CR, CRu, or PR was first achieved until documented tumor progression, or until the participant died from any cause, whichever occurred first. Participants who did not progress or die at the time of analysis were censored at the last assessment date that the participant was known to be progression-free. Participants who received a new treatment without documented progression were censored at the last assessment date that the participant was known to be progression-free. The analysis population included participants with an overall response.
    End point type
    Secondary
    End point timeframe
    From date of randomization to the data cut-off date of 07 March 2014; median study duration was 70.7 weeks for the lenalidomide arm and 69.3 weeks for the investigators choice arm
    End point values
    		 Lenalidomide Investigators Choice
    Number of subjects analysed
    68
    9
    Units: Weeks
        median (confidence interval 95%)
    69.6 (41.1 to 86.7)
    45.1 (36.3 to 80.9)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Lenalidomide v Investigators Choice
    Number of subjects included in analysis
    77
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.421
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.29
         upper limit
    		 1.68

    Secondary: Kaplan Meier Estimate for Duration of Response as Assessed by the Investigator at the Final Analysis

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    End point title
    		 Kaplan Meier Estimate for Duration of Response as Assessed by the Investigator at the Final Analysis
    End point description
    Duration of response was defined as the time from when the first response of CR, CRu, or PR was first achieved until documented tumor progression, or until the participant died from any cause, whichever occurred first. Participants who did not progress or die at the time of analysis were censored at the last assessment date that the participant was known to be progression-free. Participants who received a new treatment without documented progression were censored at the last assessment date that the participant was known to be progression-free. The analysis population included participants with an overall response.
    End point type
    Secondary
    End point timeframe
    From date of randomization to the study discontinuation date of 09 October 2018; median study duration was 103.9 weeks for lenalidomide and 87.0 weeks for the investigator choice arm
    End point values
    		 Lenalidomide Investigators Choice
    Number of subjects analysed
    78
    19
    Units: Weeks
        median (confidence interval 95%)
    70.1 (47.0 to 98.0)
    91.7 (28.3 to 130.1)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Lenalidomide v Investigators Choice
    Number of subjects included in analysis
    97
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.875
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.95
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.52
         upper limit
    		 1.74

    Secondary: Percentage of Participants with a Complete Response, Unconfirmed Complete Response, Partial Response and Stable Disease According to the IRC Central Review

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    End point title
    		 Percentage of Participants with a Complete Response, Unconfirmed Complete Response, Partial Response and Stable Disease According to the IRC Central Review
    End point description
    Tumor control rate was defined as the percentage of participants with a complete response (CR), unconfirmed complete response (CRu), partial response (PR) and stable disease (SD). Tumor Response was assessed by a modification of the International Lymphoma Workshop Response Criteria, IWRC, Cheson, 1999); CR is defined as the disappearance of all clinical and radiographic evidence of disease; CRu is defined as a CR, with a 1) residual lymph node mass >1.5 cm that has decreased by 75% in the sum of the product of the diameters (SPD). Individual nodes previously confluent decreased by more than 75% in the SPD compared with original mass; 2) indeterminate bone marrow; PR = is defined ≥50% decrease in 6 largest nodes or nodal masses. Stable disease (SD) is defined as less than a PR (see above) but is not progressive disease or relapsed disease. ITT population includes all randomized participants.
    End point type
    Secondary
    End point timeframe
    From date of randomization to the data cut-off date of 07 March 2014; median treatment duration was 24.3 weeks for the lenalidomide arm and 13.1 weeks for the investigators choice arm
    End point values
    		 Lenalidomide Investigators Choice
    Number of subjects analysed
    170
    84
    Units: Percentage of Participants
        number (confidence interval 95%)
    69.4 (61.89 to 76.24)
    63.1 (51.87 to 73.37)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Lenalidomide v Investigators Choice
    Number of subjects included in analysis
    254
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.313
    Method
    		 Chi-squared
    Confidence interval

    Secondary: Percentage of Participants with a Complete Response, Unconfirmed Complete Response, Partial Response and Stable Disease at the Final Analysis

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    End point title
    		 Percentage of Participants with a Complete Response, Unconfirmed Complete Response, Partial Response and Stable Disease at the Final Analysis
    End point description
    Tumor control rate was defined as the percentage of participants with a complete response (CR), unconfirmed complete response (CRu), partial response (PR) and stable disease (SD). Tumor Response was assessed by a modification of the International Lymphoma Workshop Response Criteria, IWRC, Cheson, 1999); CR is defined as the disappearance of all clinical and radiographic evidence of disease; CRu is defined as a CR, with a 1) residual lymph node mass >1.5 cm that has decreased by 75% in the sum of the product of the diameters (SPD). Individual nodes previously confluent decreased by more than 75% in the SPD compared with original mass; 2) indeterminate bone marrow; PR = is defined ≥50% decrease in 6 largest nodes or nodal masses. Stable disease (SD) is defined as less than a PR (see above) but is not progressive disease or relapsed disease. ITT population includes all randomized participants.
    End point type
    Secondary
    End point timeframe
    From date of randomization to the discontinuation date of 09 October 2018; median treatment duration was 24.3 weeks for the lenalidomide arm and 13.1 weeks for the investigators choice arm
    End point values
    		 Lenalidomide Investigators Choice
    Number of subjects analysed
    170
    84
    Units: Percentage of participants
        number (confidence interval 95%)
    70.0 (62.51 to 76.78)
    65.5 (54.31 to 75.52)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Lenalidomide v Investigators Choice
    Number of subjects included in analysis
    254
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.465
    Method
    		 Chi-squared
    Confidence interval

    Secondary: Kaplan Meier Estimate of Time to Progression According to the IRC Central Review

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    End point title
    		 Kaplan Meier Estimate of Time to Progression According to the IRC Central Review
    End point description
    Time to progression (TTP) was defined as the time from randomization until objective tumor progression. Time to progression did not include deaths. Participants without progression at the time of analysis were censored at the last assessment date that the participant was known to be progression-free. Participants who received a new anti-lymphoma treatment without documented progression were censored at the last assessment date that the participant was known to be progression-free. ITT population includes all randomized participants.
    End point type
    Secondary
    End point timeframe
    From date of randomization to the data cut-off date of 07 March 2014; median study duration was 70.7 weeks for the lenalidomide arm and 69.3 weeks for the investigators choice arm
    End point values
    		 Lenalidomide Investigators Choice
    Number of subjects analysed
    170
    84
    Units: Weeks
        median (confidence interval 95%)
    39.3 (24.3 to 52.9)
    24.7 (15.9 to 30.1)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Lenalidomide v Investigators Choice
    Number of subjects included in analysis
    254
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.005
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.62
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.45
         upper limit
    		 0.87

    Secondary: Kaplan Meier Estimate of Time to Progression as Assessed by the Investigator at the Final Analysis

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    End point title
    		 Kaplan Meier Estimate of Time to Progression as Assessed by the Investigator at the Final Analysis
    End point description
    Time to progression (TTP) was defined as the time from randomization until objective tumor progression. Time to progression did not include deaths. Participants without progression at the time of analysis were censored at the last assessment date that the participant was known to be progression-free. Participants who received a new anti-lymphoma treatment without documented progression were censored at the last assessment date that the participant was known to be progression-free. ITT population includes all randomized participants.
    End point type
    Secondary
    End point timeframe
    From date of randomization to the study discontinuation date of 09 October 2018; median study duration was 103.9 weeks for lenalidomide and 87.0 weeks for the investigator choice arm
    End point values
    		 Lenalidomide Investigators Choice
    Number of subjects analysed
    170
    84
    Units: Weeks
        median (confidence interval 95%)
    39.3 (25.1 to 61.0)
    24.7 (15.9 to 36.7)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Lenalidomide v Investigators Choice
    Number of subjects included in analysis
    254
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.003
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.63
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.46
         upper limit
    		 0.86

    Secondary: Kaplan Meier Estimate of Time to Treatment Failure (TTF) as Assessed by the Investigator

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    End point title
    		 Kaplan Meier Estimate of Time to Treatment Failure (TTF) as Assessed by the Investigator
    End point description
    Time to treatment failure was defined as the time from the first dose of study drug to discontinuation of treatment for any reason, including disease progression assessed by the investigator, treatment toxicity, or death. Participants who were on-treatment or completed the treatment according to the protocol were censored at the last date of drug intake. Includes all treated participants.
    End point type
    Secondary
    End point timeframe
    From the date of the first treatment to the data cut-off date of 07 March 2014; median treatment duration was 24.3 weeks for the lenalidomide arm and 13.1 weeks for the investigators choice arm
    End point values
    		 Lenalidomide Investigators Choice
    Number of subjects analysed
    167
    83
    Units: weeks
        median (confidence interval 95%)
    24.4 (17.1 to 37.6)
    17.9 (14.1 to 24.9)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Lenalidomide v Investigators Choice
    Number of subjects included in analysis
    250
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.046
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.74
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.54
         upper limit
    		 1

    Secondary: Kaplan Meier Estimate of Time to Treatment Failure as Assessed by the Investigator at the Final Analysis

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    End point title
    		 Kaplan Meier Estimate of Time to Treatment Failure as Assessed by the Investigator at the Final Analysis
    End point description
    Time to treatment failure was defined as the time from the first dose of study drug to discontinuation of treatment for any reason, including disease progression assessed by the investigator, treatment toxicity, or death. Participants who were on-treatment or completed the treatment according to the protocol were censored at the last date of drug intake. Includes all treated participants.
    End point type
    Secondary
    End point timeframe
    From date of first dose of treatment to the study discontinuation date of 09 October 2018; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm
    End point values
    		 Lenalidomide Investigators Choice
    Number of subjects analysed
    167
    83
    Units: weeks
        median (confidence interval 95%)
    24.4 (17.1 to 37.6)
    17.9 (14.1 to 24.9)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Lenalidomide v Investigators Choice
    Number of subjects included in analysis
    250
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.095
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.78
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.58
         upper limit
    		 1.05

    Secondary: Kaplan Meier Estimate of Time to First Response (TTFR) According to the IRC Central Review

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    End point title
    		 Kaplan Meier Estimate of Time to First Response (TTFR) According to the IRC Central Review
    End point description
    Time to Response was defined as the time from first dose of study drug to the date of the first response (having at least a PR) and was calculated only for responding participants). Participants with progression at the time of analysis were censored at the first assessment date that the participant was known to have progressed. Participants with SD at the time of analysis were censored at the last assessment date that the participant was known to be progression-free. ITT population includes all randomized participants.
    End point type
    Secondary
    End point timeframe
    From randomization of study drug to time of first documented PR or better response; up to data cut-off date of 07 March 2014; median treatment duration was 24.3 weeks for the lenalidomide arm and 13.1 weeks for the investigators choice arm
    End point values
    		 Lenalidomide Investigators Choice
    Number of subjects analysed
    170
    84 [3]
    Units: Weeks
        median (confidence interval 95%)
    18.7 (16.7 to 49.7)
    99999 (63.9 to 99999)
    Notes
    [3] - 99999 = Not estimable due to the low number of participants with a response.
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Lenalidomide v Investigators Choice
    Number of subjects included in analysis
    254
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    3.91
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.95
         upper limit
    		 7.85

    Secondary: Kaplan Meier Estimate of Time to First Response as Assessed by the Investigator at the Final Analysis

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    End point title
    		 Kaplan Meier Estimate of Time to First Response as Assessed by the Investigator at the Final Analysis
    End point description
    Time to first response was defined as the time from first dose of study drug to the date of the first response (having at least a PR). Participants with progression at the time of analysis were censored at the first assessment date that the participant was known to have progressed. Participants with SD at the time of analysis were censored at the last assessment date that the subject was known to be progression-free. ITT population includes all randomized participants.
    End point type
    Secondary
    End point timeframe
    From date of randomization to the study discontinuation date of 09 October 2018; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm
    End point values
    		 Lenalidomide Investigators Choice
    Number of subjects analysed
    170
    84 [4]
    Units: Weeks
        median (confidence interval 95%)
    23.9 (16.7 to 25.6)
    40.0 (25.6 to 99999)
    Notes
    [4] - 99999 = Not estimable due to the low number of participants with a response.
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Lenalidomide v Investigators Choice
    Number of subjects included in analysis
    254
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.004
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    2.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.24
         upper limit
    		 3.42

    Secondary: Kaplan Meier Estimate for Overall Survival (OS) According to the IRC Central Review

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    End point title
    		 Kaplan Meier Estimate for Overall Survival (OS) According to the IRC Central Review
    End point description
    Overall survival was defined as the time from randomization until death from any cause. Participants alive or lost to follow-up at the time of analysis were censored at the last date they were known to be alive. ITT population included all randomized participants.
    End point type
    Secondary
    End point timeframe
    From date of randomization to the data cut-off date of 07 March 2014; overall median follow-up was 93.9 weeks
    End point values
    		 Lenalidomide Investigators Choice
    Number of subjects analysed
    170
    84
    Units: weeks
        median (confidence interval 95%)
    121.0 (86.7 to 160.4)
    91.7 (69.4 to 125.6)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Lenalidomide v Investigators Choice
    Number of subjects included in analysis
    254
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.519
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.89
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.62
         upper limit
    		 1.28

    Secondary: Kaplan Meier Estimate for Overall Survival as Assessed by the Investigator at the Final Analysis

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    End point title
    		 Kaplan Meier Estimate for Overall Survival as Assessed by the Investigator at the Final Analysis
    End point description
    Overall survival was defined as the time from randomization until death from any cause. Participants alive or lost to follow-up at the time of analysis were censored at the last date they were known to be alive. ITT population included all randomized participants.
    End point type
    Secondary
    End point timeframe
    From randomization to progression of disease or death; up to the study discontinuation date of 09 October 2018; overall median follow-up time was 285 weeks
    End point values
    		 Lenalidomide Investigators Choice
    Number of subjects analysed
    170
    84
    Units: weeks
        median (confidence interval 95%)
    120.6 (98.1 to 153.0)
    91.7 (69.4 to 137.3)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Lenalidomide v Investigators Choice
    Number of subjects included in analysis
    254
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.558
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.91
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.67
         upper limit
    		 1.25

    Secondary: Number of Participants with Treatment Emergent Adverse Events (TEAE)

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    End point title
    		 Number of Participants with Treatment Emergent Adverse Events (TEAE)
    End point description
    Adverse events were assessed using National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 3: according to the following scale: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe and Undesirable, Grade 4 = Life-threatening or Disabling, and Grade 5 = Death; Serious AEs (SAEs) are those that resulted in death, were life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly, or resulted in an important medical event that may have jeopardized the patient or required medical or surgical intervention to prevent one of the outcomes listed above. after the first dose of study drug and within 28 days after the last dose. A TEAE = any AE occurring or worsening on or after the first dose of study drug and within 28 days after the last dose. The safety population included those who received at least one dose of study drug (either LEN or investigator's choice).
    End point type
    Secondary
    End point timeframe
    From the date of the first dose of study drug to 28 days after the last dose, up to the study discontinuation date of 09 October 2018; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigators choice arm
    End point values
    		 Lenalidomide Investigators Choice
    Number of subjects analysed
    167
    83
    Units: Participants
        Any TEAE
    159
    69
        Any TEAE Grade 3 AE
    126
    49
        Any TEAE Grade 4 AE
    56
    29
        Any TEAE Grade 5 AE
    15
    2
        Any TEAE Related to the IP
    141
    51
        Any Grade 3 AE Related to IP
    106
    36
        Any Grade 4 AE Related to IP
    46
    19
        Any Grade 5 AE Related to IP
    0
    0
        Any Serious Adverse Event (SAE)
    75
    22
        Any SAE Related to IP
    38
    12
        Any TEAE Leading to Stopping of IP
    31
    14
        Any Treatment Related AE Leading to Stopping IP
    18
    7
        TEAE Leading to Dose Reduction/Interruption
    114
    33
        Related AE Leading to Dose Reduct/Interruption
    103
    29
        TEAE Leading to Dose Reduction
    72
    13
        Related AE Leading to Dose Reduction
    69
    10
        TEAE Leading to Dose Interruption
    110
    28
        Related AE Leading to Dose Interruption
    98
    25
    No statistical analyses for this end point

    Secondary: Mean Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain

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    End point title
    		 Mean Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain
    End point description
    The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Physical Functioning Scale ranges from 0 to 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement. Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.
    End point type
    Secondary
    End point timeframe
    Baseline (BL) known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation (D/C); median IP duration = 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
    End point values
    		 Lenalidomide Investigators Choice
    Number of subjects analysed
    160
    74
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline
    71.8 ( 22.35 )
    78.9 ( 17.38 )
        Change from BL to Cycle 3 Day 1; N = 104, 43
    -0.5 ( 15.47 )
    -3.7 ( 16.22 )
        Change from BL to Cycle 5 Day 1; N = 70, 26
    1.6 ( 15.18 )
    -2.1 ( 19.02 )
        Change from BL to Cycle 7 Day 1; N = 56, 8
    2.4 ( 16.74 )
    4.2 ( 16.69 )
        Change from BL to Cycle 9 Day 1; N = 46, 6
    2.8 ( 18.08 )
    11.1 ( 11.67 )
        Change from BL to IP Discontinuation; N = 62, 43
    -5.6 ( 19.46 )
    -5.1 ( 17.14 )
    No statistical analyses for this end point

    Secondary: Maximum Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain to Treatment Discontinuation Visit

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    End point title
    		 Maximum Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain to Treatment Discontinuation Visit
    End point description
    The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Physical Functioning Scale ranges from 0 to 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement. Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.
    End point type
    Secondary
    End point timeframe
    Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
    End point values
    		 Lenalidomide Investigators Choice
    Number of subjects analysed
    124
    57
    Units: units on a scale
        arithmetic mean (standard deviation)
    3.4 ( 18.70 )
    -1.8 ( 17.57 )
    No statistical analyses for this end point

    Secondary: Mean Change From Baseline in the EORTC QLQ-C30 Role Functioning Domain

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    End point title
    		 Mean Change From Baseline in the EORTC QLQ-C30 Role Functioning Domain
    End point description
    The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Role Functioning Scale ranges from 0 to 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement. Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.
    End point type
    Secondary
    End point timeframe
    Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
    End point values
    		 Lenalidomide Investigators Choice
    Number of subjects analysed
    161
    74
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (BL)
    71.5 ( 31.10 )
    73.9 ( 25.60 )
        Change from BL to Cycle 3 Day 1; N = 105, 43
    -4.8 ( 26.12 )
    3.5 ( 21.69 )
        Change from BL to Cycle 5 Day 1; N = 71, 26
    1.4 ( 26.09 )
    -6.4 ( 30.21 )
        Change from BL to Cycle 7 Day 1; N = 57, 8
    0.3 ( 26.44 )
    0.0 ( 38.83 )
        Change from BL to Cycle 9 Day 1; N = 47, 6
    1.8 ( 26.75 )
    13.9 ( 19.48 )
        Change from BL to IP Discontinuation; N =62, 43
    -9.1 ( 29.05 )
    -4.3 ( 31.09 )
    No statistical analyses for this end point

    Secondary: Maximum Change From Baseline in the EORTC QLQ-C30 Role Functioning Domain to Treatment Discontinuation Visit

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    End point title
    		 Maximum Change From Baseline in the EORTC QLQ-C30 Role Functioning Domain to Treatment Discontinuation Visit
    End point description
    The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Role Functioning Scale ranges from 0 to 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.
    End point type
    Secondary
    End point timeframe
    Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
    End point values
    		 Lenalidomide Investigators Choice
    Number of subjects analysed
    160
    74
    Units: units on a scale
        arithmetic mean (standard deviation)
    3.1 ( 28.43 )
    5.0 ( 27.09 )
    No statistical analyses for this end point

    Secondary: Mean Change From Baseline in the EORTC QLQ-C30 Cognitive Functioning Domain

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    End point title
    		 Mean Change From Baseline in the EORTC QLQ-C30 Cognitive Functioning Domain
    End point description
    The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Cognitive Functioning Domain ranges from 0 to 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement. Hide Analysis Population Description Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.
    End point type
    Secondary
    End point timeframe
    Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
    End point values
    		 Lenalidomide Investigators Choice
    Number of subjects analysed
    161
    74
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (BL)
    84.6 ( 19.86 )
    83.6 ( 20.18 )
        Change from BL to Cycle 3 Day 1; N = 105, 43
    0.0 ( 16.34 )
    -2.3 ( 13.89 )
        Change from BL to Cycle 5 Day 1; N = 71, 26
    -1.9 ( 17.72 )
    1.3 ( 14.85 )
        Change from BL to Cycle 7 Day 1; N = 57, 8
    -3.2 ( 19.27 )
    4.2 ( 14.77 )
        Change from BL to Cycle 9 Day 1; N = 47, 6
    -2.5 ( 18.05 )
    5.6 ( 13.61 )
        Change from BL to IP Discontinuation; N=62, 43
    -5.1 ( 19.46 )
    -2.3 ( 15.68 )
    No statistical analyses for this end point

    Secondary: Maximum Change From Baseline in the EORTC QLQ-C30 Cognitive Functioning Domain to Treatment Discontinuation Visit

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    End point title
    		 Maximum Change From Baseline in the EORTC QLQ-C30 Cognitive Functioning Domain to Treatment Discontinuation Visit
    End point description
    The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Cognitive Functioning Scale ranges from 0 to 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement. Hide Analysis Population Description Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.
    End point type
    Secondary
    End point timeframe
    Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
    End point values
    		 Lenalidomide Investigators Choice
    Number of subjects analysed
    160
    74
    Units: units on a scale
        arithmetic mean (standard deviation)
    3.2 ( 17.92 )
    2.9 ( 14.13 )
    No statistical analyses for this end point

    Secondary: Mean Change From Baseline in the EORTC QLQ-C30 Social Functioning Domain

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    End point title
    		 Mean Change From Baseline in the EORTC QLQ-C30 Social Functioning Domain
    End point description
    The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Social Functioning Domain ranges from 0 to 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement. Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.
    End point type
    Secondary
    End point timeframe
    Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
    End point values
    		 Lenalidomide Investigators Choice
    Number of subjects analysed
    161
    74
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (BL)
    74.9 ( 28.39 )
    78.4 ( 26.85 )
        Change from BL to Cycle 3 Day 1; N = 105, 43
    -1.0 ( 20.39 )
    -1.2 ( 22.54 )
        Change from BL to Cycle 5 Day 1; N = 71, 26
    1.6 ( 19.75 )
    -4.5 ( 29.27 )
        Change from Baseline to Cycle 7 Day 1; N = 57, 8
    -1.5 ( 25.06 )
    2.1 ( 28.78 )
        Change from BL to Cycle 9 Day 1; N = 47, 6
    4.3 ( 22.11 )
    0.0 ( 23.57 )
        Change from BL to IP Discontinuation; N=62, 43
    -5.1 ( 24.63 )
    -2.7 ( 20.87 )
    No statistical analyses for this end point

    Secondary: Maximum Change From Baseline in the EORTC QLQ-C30 Social Functioning Domain to Treatment Discontinuation Visit

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    End point title
    		 Maximum Change From Baseline in the EORTC QLQ-C30 Social Functioning Domain to Treatment Discontinuation Visit
    End point description
    The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Social Functioning Scale ranges from 0 to 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement. Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.
    End point type
    Secondary
    End point timeframe
    Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
    End point values
    		 Lenalidomide Investigators Choice
    Number of subjects analysed
    161
    74
    Units: units on a scale
        arithmetic mean (standard deviation)
    5.1 ( 20.87 )
    3.8 ( 19.92 )
    No statistical analyses for this end point

    Secondary: Mean Change From Baseline in the EORTC QLQ-C30 Fatigue Domain

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    End point title
    		 Mean Change From Baseline in the EORTC QLQ-C30 Fatigue Domain
    End point description
    The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Fatigue Domain was scored between 0 and 100, with a higher score representing worse symptomatic expression. Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.
    End point type
    Secondary
    End point timeframe
    Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
    End point values
    		 Lenalidomide Investigators Choice
    Number of subjects analysed
    161
    74
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (BL)
    40.2 ( 26.67 )
    39.2 ( 23.50 )
        Change from BL to Cycle 3 Day 1; N = 105, 43
    0.1 ( 21.72 )
    2.1 ( 22.12 )
        Change from BL to Cycle 5 Day 1; N = 71, 26
    -3.2 ( 20.84 )
    3.4 ( 25.68 )
        Change from BL to Cycle 7 Day 1; N = 57, 8
    -1.0 ( 21.03 )
    -6.9 ( 25.85 )
        Change from BL to Cycle 9 Day 1; N = 47, 6
    -3.9 ( 26.64 )
    -7.4 ( 25.01 )
        Change from BL to IP Discontinuation; N =62,43
    5.2 ( 21.48 )
    2.6 ( 24.11 )
    No statistical analyses for this end point

    Secondary: Maximum Change From Baseline in the EORTC QLQ-C30 Fatigue Domain to Treatment Discontinuation Visit

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    End point title
    		 Maximum Change From Baseline in the EORTC QLQ-C30 Fatigue Domain to Treatment Discontinuation Visit
    End point description
    The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Fatigue Scale was scored between 0 and 100, with a higher score representing worse symptomatic expression. Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.
    End point type
    Secondary
    End point timeframe
    Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
    End point values
    		 Lenalidomide Investigators Choice
    Number of subjects analysed
    160
    74
    Units: units on a scale
        arithmetic mean (standard deviation)
    -4.9 ( 22.76 )
    -2.9 ( 23.24 )
    No statistical analyses for this end point

    Secondary: Mean Change From Baseline in the EORTC QLQ-C30 Pain Domain

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    End point title
    		 Mean Change From Baseline in the EORTC QLQ-C30 Pain Domain
    End point description
    The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Pain Domain was scored between 0 and 100, with a higher score representing worse symptomatic expression. Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.
    End point type
    Secondary
    End point timeframe
    Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
    End point values
    		 Lenalidomide Investigators Choice
    Number of subjects analysed
    160
    74
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (BL)
    22.6 ( 25.86 )
    13.7 ( 20.15 )
        Change from BL to Cycle 3 Day 1; N = 104, 43
    -2.2 ( 19.99 )
    -1.2 ( 25.30 )
        Change from BL to Cycle 5 Day 1; N = 70, 26
    -0.2 ( 24.82 )
    -2.6 ( 20.38 )
        Change from BL to Cycle 7 Day 1; N = 57, 8
    3.2 ( 26.99 )
    0.0 ( 19.92 )
        Change from BL to Cycle 9 Day 1; N = 47, 6
    -3.2 ( 25.92 )
    -2.8 ( 6.80 )
        Change from BL to IP Discontinuation; N=61,43
    4.6 ( 26.38 )
    3.5 ( 22.29 )
    No statistical analyses for this end point

    Secondary: Maximum Change From Baseline in the EORTC QLQ-C30 Pain Domain to Treatment Discontinuation Visit

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    End point title
    		 Maximum Change From Baseline in the EORTC QLQ-C30 Pain Domain to Treatment Discontinuation Visit
    End point description
    The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Pain Scale was scored between 0 and 100, with a higher score representing worse symptomatic expression. Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.
    End point type
    Secondary
    End point timeframe
    Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and time of discontinuation from treatment visit.Up to final data cut-0ff date of 07 March 2014
    End point values
    		 Lenalidomide Investigators Choice
    Number of subjects analysed
    160
    74
    Units: units on a scale
        arithmetic mean (standard deviation)
    -5.8 ( 24.61 )
    -3.5 ( 21.30 )
    No statistical analyses for this end point

    Secondary: Mean Change From Baseline in the EORTC QLQ-C30 Nausea / Vomiting Domain

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    End point title
    		 Mean Change From Baseline in the EORTC QLQ-C30 Nausea / Vomiting Domain
    End point description
    The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Nausea and Vomiting Domain was scored between 0 and 100, with a higher score representing worse symptomatic expression. Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.
    End point type
    Secondary
    End point timeframe
    Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
    End point values
    		 Lenalidomide Investigators Choice
    Number of subjects analysed
    161
    74
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (BL)
    4.9 ( 10.31 )
    3.8 ( 11.22 )
        Change from BL to Cycle 3 Day 1; N = 105, 43
    2.5 ( 14.39 )
    0.4 ( 10.60 )
        Change from BL to Cycle 5 Day 1; N = 71, 26
    2.6 ( 11.83 )
    5.8 ( 21.57 )
        Change from BL to Cycle 7 Day 1; N = 57, 8
    5.3 ( 17.30 )
    2.1 ( 22.60 )
        Change from BL to Cycle 9 Day 1; N = 47, 6
    -0.7 ( 10.40 )
    2.8 ( 6.80 )
        Change from BL to IP Discontinuation; N =62, 43
    0.5 ( 9.99 )
    6.6 ( 18.59 )
    No statistical analyses for this end point

    Secondary: Maximum Change From Baseline in the EORTC QLQ-C30 Nausea and Vomiting Domain to Treatment Discontinuation Visit

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    End point title
    		 Maximum Change From Baseline in the EORTC QLQ-C30 Nausea and Vomiting Domain to Treatment Discontinuation Visit
    End point description
    The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Nausea and Vomiting Scale was scored between 0 and 100, with a high score representing worse symptomatic expression. Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.
    End point type
    Secondary
    End point timeframe
    Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
    End point values
    		 Lenalidomide Investigators Choice
    Number of subjects analysed
    161
    74
    Units: units on a scale
        arithmetic mean (standard deviation)
    -2.3 ( 8.82 )
    -0.6 ( 8.31 )
    No statistical analyses for this end point

    Secondary: Mean Change From Baseline in the EORTC QLQ-C30 Constipation

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    End point title
    		 Mean Change From Baseline in the EORTC QLQ-C30 Constipation
    End point description
    The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Constipation Domain was scored between 0 and 100, with a high score representing worse symptomatic expression. Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.
    End point type
    Secondary
    End point timeframe
    Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
    End point values
    		 Lenalidomide Investigators Choice
    Number of subjects analysed
    160
    74
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (BL)
    12.5 ( 23.27 )
    8.6 ( 19.16 )
        Change from BL to Cycle 3 Day 1; N = 105, 43
    6.3 ( 27.38 )
    -0.8 ( 18.53 )
        Change from BL to Cycle 5 Day 1; N = 71, 26
    4.2 ( 25.78 )
    1.3 ( 17.59 )
        Change from BL to Cycle 7 Day 1; N = 57, 8
    3.5 ( 27.95 )
    0.0 ( 30.86 )
        Change from BL to Cycle 9 Day 1; 47, 6
    -0.7 ( 20.25 )
    0.0 ( 21.08 )
        Change from BL to IP Discontinuation; N=62, 43
    10.2 ( 32.27 )
    0.8 ( 21.19 )
    No statistical analyses for this end point

    Secondary: Maximum Change From Baseline in the EORTC QLQ-C30 Constipation Domain to Treatment Discontinuation Visit

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    End point title
    		 Maximum Change From Baseline in the EORTC QLQ-C30 Constipation Domain to Treatment Discontinuation Visit
    End point description
    The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Constipation Scale was scored between 0 and 100, with a higher score representing worse symptomatic expression. Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.
    End point type
    Secondary
    End point timeframe
    Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
    End point values
    		 Lenalidomide Investigators Choice
    Number of subjects analysed
    160
    74
    Units: units on a scale
        arithmetic mean (standard deviation)
    -0.3 ( 27.60 )
    -3.5 ( 16.29 )
    No statistical analyses for this end point

    Secondary: Mean Change From Baseline in the EORTC QLQ-C30 Diarhoea

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    End point title
    		 Mean Change From Baseline in the EORTC QLQ-C30 Diarhoea
    End point description
    The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Diarhoea Domain was scored between 0 and 100, with a higher score representing worse symptomatic expression. Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.
    End point type
    Secondary
    End point timeframe
    Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
    End point values
    		 Lenalidomide Investigators Choice
    Number of subjects analysed
    161
    74
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (BL)
    15.7 ( 27.15 )
    12.6 ( 20.42 )
        Change from BL to Cycle 3 Day 1; N = 105, 43
    -3.5 ( 25.71 )
    -3.1 ( 21.60 )
        Change from BL to Cycle 5 Day 1; N = 71, 26
    -4.2 ( 29.78 )
    1.3 ( 22.07 )
        Change from BL to Cycle 7 Day 1; N = 55, 8
    2.4 ( 32.62 )
    -4.2 ( 33.03 )
        Change from BL to Cycle 9 Day 1; 47, 6
    -2.1 ( 22.42 )
    0.0 ( 36.51 )
        Change from BL to IP Discontinuation; N=62, 43
    1.6 ( 30.44 )
    0.0 ( 25.20 )
    No statistical analyses for this end point

    Secondary: Maximum Change From Baseline in the EORTC QLQ-C30 Diarhoea Domain to Treatment Discontinuation Visit

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    End point title
    		 Maximum Change From Baseline in the EORTC QLQ-C30 Diarhoea Domain to Treatment Discontinuation Visit
    End point description
    The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Diarhoea Scale was scored between 0 and 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement. Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.
    End point type
    Secondary
    End point timeframe
    Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and time of discontinuation from treatment visit.Up to final data cut-0ff date of 07 March 2014
    End point values
    		 Lenalidomide Investigators Choice
    Number of subjects analysed
    161
    74
    Units: units on a scale
        least squares mean (standard deviation)
    -7.2 ( 25.25 )
    -5.8 ( 21.93 )
    No statistical analyses for this end point

    Secondary: Mean Change From Baseline in the EORTC QLQ-C30 Insomnia Domain

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    End point title
    		 Mean Change From Baseline in the EORTC QLQ-C30 Insomnia Domain
    End point description
    The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Insomnia Domain was scored between 0 and 100, with a higher score representing worse symptomatic expression. Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.
    End point type
    Secondary
    End point timeframe
    Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
    End point values
    		 Lenalidomide Investigators Choice
    Number of subjects analysed
    160
    74
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (BL)
    29.4 ( 30.69 )
    25.7 ( 27.34 )
        Change from BL to Cycle 3 Day 1; N = 105, 43
    -7.6 ( 27.06 )
    -4.7 ( 31.36 )
        Change from BL to Cycle 5 Day 1; N = 71, 26
    -5.2 ( 24.97 )
    -6.4 ( 32.69 )
        Change from BL to Cycle 7 Day 1; N = 57, 8
    -1.8 ( 29.83 )
    -16.7 ( 39.84 )
        Change from BL to Cycle 9 Day 1; N = 47, 6
    -7.1 ( 30.25 )
    -16.7 ( 40.82 )
        Change from BL to IP Discontinuation; N=62, 43
    -3.2 ( 28.76 )
    0.8 ( 22.41 )
    No statistical analyses for this end point

    Secondary: Maximum Change From Baseline in the EORTC QLQ-C30 Insomnia Domain to Treatment Discontinuation Visit

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    End point title
    		 Maximum Change From Baseline in the EORTC QLQ-C30 Insomnia Domain to Treatment Discontinuation Visit
    End point description
    The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Dyspnoea Domain was scored between 0 and 100, with a high score representing worse symptomatic expression. Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.
    End point type
    Secondary
    End point timeframe
    Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
    End point values
    		 Lenalidomide Investigators Choice
    Number of subjects analysed
    160
    74
    Units: units on a scale
        arithmetic mean (standard deviation)
    -12.8 ( 28.64 )
    -7.6 ( 30.87 )
    No statistical analyses for this end point

    Secondary: Mean Change From Baseline in the EORTC QLQ-C30 Dyspnoea Domain to Treatment Discontinuation Visit

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    End point title
    		 Mean Change From Baseline in the EORTC QLQ-C30 Dyspnoea Domain to Treatment Discontinuation Visit
    End point description
    The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Dyspnoea Domain was scored between 0 and 100, with a high score representing worse symptomatic expression. Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.
    End point type
    Secondary
    End point timeframe
    Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
    End point values
    		 Lenalidomide Investigators Choice
    Number of subjects analysed
    160
    74
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (BL)
    26.5 ( 28.98 )
    21.2 ( 28.97 )
        Change from BL to Cycle 3 Day 1; N = 103, 43
    -1.6 ( 27.76 )
    -0.8 ( 29.54 )
        Change from BL to Cycle 5 Day 1; N = 70, 26
    -1.4 ( 26.88 )
    0.0 ( 33.99 )
        Change from BL to Cycle 7 Day 1; N = 57, 8
    -2.9 ( 25.42 )
    4.2 ( 48.59 )
        Change from BL to Cycle 9 Day 1; N = 47, 6
    1.4 ( 31.05 )
    5.6 ( 25.09 )
        Change from BL to IP Discontinuation; N=61, 43
    6.0 ( 28.22 )
    0.8 ( 23.56 )
    No statistical analyses for this end point

    Secondary: Maximum Change From Baseline in the EORTC QLQ-C30 Dyspnoea Domain to Treatment Discontinuation Visit

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    End point title
    		 Maximum Change From Baseline in the EORTC QLQ-C30 Dyspnoea Domain to Treatment Discontinuation Visit
    End point description
    The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Dyspnoea Domain to Treatment Scale was scored between 0 and 100, with a higher score representing worse symptomatic expression. Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.
    End point type
    Secondary
    End point timeframe
    Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
    End point values
    		 Lenalidomide Investigators Choice
    Number of subjects analysed
    160
    74
    Units: units on a scale
        arithmetic mean (standard deviation)
    -7.3 ( 25.70 )
    -5.8 ( 27.55 )
    No statistical analyses for this end point

    Secondary: Mean Change From Baseline in the EORTC QLQ-C30 Appetite Loss Domain to Treatment Discontinuation Visit

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    End point title
    		 Mean Change From Baseline in the EORTC QLQ-C30 Appetite Loss Domain to Treatment Discontinuation Visit
    End point description
    The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Appetite Loss Domain was scored between 0 and 100, with a higher score representing worse symptomatic expression. Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.
    End point type
    Secondary
    End point timeframe
    Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
    End point values
    		 Lenalidomide Investigators Choice
    Number of subjects analysed
    160
    74
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (BL)
    18.1 ( 27.69 )
    16.2 ( 26.02 )
        Change from BL to Cycle 3 Day 1; N = 105, 43
    2.5 ( 31.25 )
    -0.8 ( 34.49 )
        Change from BL to Cycle 5 Day 1; N = 71, 26
    1.9 ( 28.67 )
    5.1 ( 43.91 )
        Change from BL to Cycle 7 Day 1; N = 57, 8
    -2.3 ( 23.45 )
    -12.5 ( 46.93 )
        Change from BL to Cycle 9 Day 1; N = 47, 6
    -4.3 ( 27.47 )
    -11.1 ( 27.22 )
        Change from BL to IP Discontinuation; N =62, 43
    4.8 ( 32.42 )
    5.4 ( 27.15 )
    No statistical analyses for this end point

    Secondary: Maximum Change From Baseline in the EORTC QLQ-C30 Appetite Loss Domain to Treatment Discontinuation Visit

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    End point title
    		 Maximum Change From Baseline in the EORTC QLQ-C30 Appetite Loss Domain to Treatment Discontinuation Visit
    End point description
    The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Appetite Loss Domain to Treatment Scale was scored between 0 and 100, with a higher score representing worse symptomatic expression. Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.
    End point type
    Secondary
    End point timeframe
    Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
    End point values
    		 Lenalidomide Investigators Choice
    Number of subjects analysed
    160
    74
    Units: units on a scale
        arithmetic mean (standard deviation)
    -4.8 ( 28.30 )
    -4.1 ( 29.59 )
    No statistical analyses for this end point

    Secondary: Mean Change From Baseline in the EORTC QLQ-C30 Financial Problems Domain to Treatment Discontinuation Visit

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    End point title
    		 Mean Change From Baseline in the EORTC QLQ-C30 Financial Problems Domain to Treatment Discontinuation Visit
    End point description
    The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Financial Problems Domain was scored between 0 and 100, with a higher score representing worse symptomatic expression. Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.
    End point type
    Secondary
    End point timeframe
    Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
    End point values
    		 Lenalidomide Investigators Choice
    Number of subjects analysed
    161
    74
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (BL)
    19.5 ( 27.78 )
    10.8 ( 19.98 )
        Change from BL to Cycle 3 Day 1; N = 105, 43
    -7.0 ( 25.61 )
    -0.8 ( 18.53 )
        Change from BL to Cycle 5 Day 1; N = 71, 26
    -7.0 ( 27.55 )
    -3.8 ( 23.71 )
        Change from BL to Cycle 7 Day 1; N = 57, 8
    -2.9 ( 33.50 )
    -4.2 ( 11.79 )
        Change from BL to Cycle 9 Day 1; N = 47, 6
    -9.2 ( 31.62 )
    -5.6 ( 13.61 )
        Change from BL to IP Discontinuation; N =62, 43
    -4.3 ( 22.97 )
    1.6 ( 19.18 )
    No statistical analyses for this end point

    Secondary: Maximum Change From Baseline in the EORTC QLQ-C30 Financial Problems Domain to Treatment Discontinuation Visit

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    End point title
    		 Maximum Change From Baseline in the EORTC QLQ-C30 Financial Problems Domain to Treatment Discontinuation Visit
    End point description
    The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Financial Problems Domain Scale was scored between 0 and 100, with a higher score representing worse symptomatic expression. Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.
    End point type
    Secondary
    End point timeframe
    Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
    End point values
    		 Lenalidomide Investigators Choice
    Number of subjects analysed
    161
    74
    Units: units on a scale
        arithmetic mean (standard deviation)
    -10.9 ( 25.32 )
    -2.3 ( 19.78 )
    No statistical analyses for this end point

    Secondary: Mean Change From Baseline in the EORTC QLQ-C30 Global Health Status / QoL Domain

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    End point title
    		 Mean Change From Baseline in the EORTC QLQ-C30 Global Health Status / QoL Domain
    End point description
    The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Global Health Status / QoL Domain was scored between 0 and 100, with a higher score representing a higher quality of life. Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.
    End point type
    Secondary
    End point timeframe
    Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
    End point values
    		 Lenalidomide Investigators Choice
    Number of subjects analysed
    160
    74
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (BL)
    59.0 ( 21.45 )
    58.4 ( 18.58 )
        Change from BL to Cycle 3 Day 1; N = 105, 43
    -3.4 ( 21.89 )
    2.3 ( 18.66 )
        Change from BL to Cycle 5 Day 1; N = 71, 26
    -0.7 ( 19.96 )
    3.2 ( 24.50 )
        Change from BL to Cycle 7 Day 1; N = 57, 8
    1.0 ( 17.04 )
    7.3 ( 29.36 )
        Change from BL to Cycle 9 Day 1; N = 47, 6
    4.3 ( 21.76 )
    8.3 ( 22.97 )
        Change from BL to IP Discontinuation;N = 62, 43
    -5.8 ( 18.76 )
    -1.0 ( 19.26 )
    No statistical analyses for this end point

    Secondary: Maximum Change From Baseline in the EORTC QLQ-C30 Global Health Status / QoL Domain to Treatment Discontinuation Visit

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    End point title
    		 Maximum Change From Baseline in the EORTC QLQ-C30 Global Health Status / QoL Domain to Treatment Discontinuation Visit
    End point description
    The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Global Health Status / QoL Domain to Treatment Scale was scored between 0 and 100, with a higher score representing a higher quality of life. Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.
    End point type
    Secondary
    End point timeframe
    Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
    End point values
    		 Lenalidomide Investigators Choice
    Number of subjects analysed
    160
    74
    Units: units on a scale
        arithmetic mean (standard deviation)
    4.6 ( 19.06 )
    5.6 ( 20.43 )
    No statistical analyses for this end point

    Secondary: Mean Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain

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    End point title
    		 Mean Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain
    End point description
    The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Emotional Domain ranges from 0 to 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement. Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.
    End point type
    Secondary
    End point timeframe
    Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
    End point values
    		 Lenalidomide Investigators Choice
    Number of subjects analysed
    161
    74
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (BL)
    73.7 ( 21.52 )
    78.5 ( 18.56 )
        Change from BL to Cycle 3 Day 1; N = 105, 43
    3.4 ( 19.64 )
    1.3 ( 20.77 )
        Change from BL to Cycle 5 Day 1; N = 71, 26
    3.6 ( 17.01 )
    1.3 ( 16.11 )
        Change from BL to Cycle 7 Day 1; N = 57, 8
    8.1 ( 20.53 )
    -3.1 ( 26.33 )
        Change from BL to Cycle 9 Day 1; N = 47, 6
    4.5 ( 21.96 )
    1.4 ( 13.35 )
        Change from BL to IP Discontinuation; N =62, 43
    -1.3 ( 22.05 )
    -1.5 ( 16.50 )
    No statistical analyses for this end point

    Secondary: Maximum Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain to Treatment Discontinuation Visit

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    End point title
    		 Maximum Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain to Treatment Discontinuation Visit
    End point description
    The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Emotional Functioning Scale ranges from 0 to 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement. Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.
    End point type
    Secondary
    End point timeframe
    Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
    End point values
    		 Lenalidomide Investigators Choice
    Number of subjects analysed
    160
    74
    Units: units on a scale
        arithmetic mean (standard deviation)
    6.9 ( 21.79 )
    3.7 ( 17.11 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From randomization of study drug to 30 days post-last dose; up to the study discontinuation date of 09 October 2018; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigators choice arm.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    20.1
    Reporting groups
    Reporting group title
    Investigators Choice
    Reporting group description
    		 Participants received a single agent investigators choice of chlorambucil 40 mg/m^2 PO every 28 days until progressive disease or toxicity, OR rituximab 375 mg/m^2 by intravenous infusion on days 1, 8, 15 and 22 of each 56-day treatment cycle until PD or toxicity, OR cytarabine 1-2 g/m^2 by IV infusion on days 1 and 2 of each 28 day treatment cycle; up to 6 cycles, OR gemcitabine 1000 mg/m^2 by IV infusion on days 1, 8 and 15 of each 28 day treatment cycle; up to 6 cycles OR oral fludarabine 40 mg/m^2 or IV fludarabine 25 mg/m^2 on days 1 through 5 of each 28-day cycle; up to 6 cycles. Participants were given the option to enter into the lenalidomide crossover phase if PD occurred and received lenalidomide 25 mg capsules daily on days 1 to 21 of each 28 day treatment cycle until PD or toxicity.

    Reporting group title
    Lenalidomide
    Reporting group description
    		 Participants received lenalidomide 25 mg capsules orally every day for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity. Participants with moderate renal insufficiency (creatinine clearance is ≥ 30 mL/min but < 60mL/min received 10 mg lenalidomide for 21 days of each 28-day cycle (Cycles 1 and 2). After Cycle 2, if the participant remained free of Grade 3 or Grade 4 toxicity, the dose was increased to 15 mg lenalidomide for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity.

    Serious adverse events
    		 Investigators Choice Lenalidomide
    Total subjects affected by serious adverse events
         subjects affected / exposed
    22 / 83 (26.51%)
    75 / 167 (44.91%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    ACUTE LYMPHOCYTIC LEUKAEMIA
         subjects affected / exposed
    0 / 83 (0.00%)
    3 / 167 (1.80%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    BASAL CELL CARCINOMA
         subjects affected / exposed
    0 / 83 (0.00%)
    2 / 167 (1.20%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CANCER PAIN
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DIFFUSE LARGE B-CELL LYMPHOMA
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    LIPOSARCOMA
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    MANTLE CELL LYMPHOMA
         subjects affected / exposed
    3 / 83 (3.61%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    MENINGIOMA BENIGN
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    METASTASES TO LUNG
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    METASTATIC SQUAMOUS CELL CARCINOMA
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SQUAMOUS CELL CARCINOMA OF SKIN
         subjects affected / exposed
    0 / 83 (0.00%)
    2 / 167 (1.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    TUMOUR FLARE
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    HAEMORRHAGE
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYPERTENSION
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYPOTENSION
         subjects affected / exposed
    0 / 83 (0.00%)
    2 / 167 (1.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    VENOUS THROMBOSIS LIMB
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    DEATH
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    FATIGUE
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    GENERAL PHYSICAL HEALTH DETERIORATION
         subjects affected / exposed
    1 / 83 (1.20%)
    3 / 167 (1.80%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    MULTIPLE ORGAN DYSFUNCTION SYNDROME
         subjects affected / exposed
    0 / 83 (0.00%)
    2 / 167 (1.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    OEDEMA PERIPHERAL
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PYREXIA
         subjects affected / exposed
    2 / 83 (2.41%)
    5 / 167 (2.99%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SUDDEN DEATH
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Immune system disorders
    DRUG HYPERSENSITIVITY
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    OEDEMA GENITAL
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    UTERINE POLYP
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    ASPIRATION
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    BRONCHITIS CHRONIC
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COUGH
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DYSPNOEA
         subjects affected / exposed
    1 / 83 (1.20%)
    3 / 167 (1.80%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    INTERSTITIAL LUNG DISEASE
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PHARYNGEAL INFLAMMATION
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PLEURAL EFFUSION
         subjects affected / exposed
    0 / 83 (0.00%)
    2 / 167 (1.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PLEURISY
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PULMONARY EMBOLISM
         subjects affected / exposed
    0 / 83 (0.00%)
    6 / 167 (3.59%)
         occurrences causally related to treatment / all
    0 / 0
    6 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    RESPIRATORY DISTRESS
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    RESPIRATORY FAILURE
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    VOCAL CORD DISORDER
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    WEIGHT DECREASED
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    FACIAL BONES FRACTURE
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    TOXICITY TO VARIOUS AGENTS
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    ACUTE CORONARY SYNDROME
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    ACUTE MYOCARDIAL INFARCTION
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ATRIAL FIBRILLATION
         subjects affected / exposed
    1 / 83 (1.20%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ATRIOVENTRICULAR BLOCK COMPLETE
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ATRIOVENTRICULAR BLOCK SECOND DEGREE
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CARDIAC ARREST
         subjects affected / exposed
    0 / 83 (0.00%)
    2 / 167 (1.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    CARDIAC FAILURE
         subjects affected / exposed
    1 / 83 (1.20%)
    2 / 167 (1.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    CARDIAC FAILURE ACUTE
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    CARDIAC FAILURE CONGESTIVE
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    CORONARY ARTERY DISEASE
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    LEFT VENTRICULAR FAILURE
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    MYOCARDIAL INFARCTION
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SUPRAVENTRICULAR TACHYCARDIA
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    TACHYCARDIA
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    CEREBRAL HAEMORRHAGE
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    CEREBROVASCULAR ACCIDENT
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HEMIANOPIA HETERONYMOUS
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ISCHAEMIC STROKE
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SEIZURE
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    TRANSIENT ISCHAEMIC ATTACK
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    ANAEMIA
         subjects affected / exposed
    2 / 83 (2.41%)
    6 / 167 (3.59%)
         occurrences causally related to treatment / all
    2 / 3
    5 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    AUTOIMMUNE HAEMOLYTIC ANAEMIA
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    FEBRILE NEUTROPENIA
         subjects affected / exposed
    2 / 83 (2.41%)
    6 / 167 (3.59%)
         occurrences causally related to treatment / all
    2 / 2
    6 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    LYMPH NODE PAIN
         subjects affected / exposed
    1 / 83 (1.20%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    NEUTROPENIA
         subjects affected / exposed
    0 / 83 (0.00%)
    6 / 167 (3.59%)
         occurrences causally related to treatment / all
    0 / 0
    7 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    THROMBOCYTOPENIA
         subjects affected / exposed
    2 / 83 (2.41%)
    3 / 167 (1.80%)
         occurrences causally related to treatment / all
    3 / 3
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    DEAFNESS BILATERAL
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    VERTIGO
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    RETINAL ARTERY OCCLUSION
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    ABDOMINAL PAIN
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ABDOMINAL WALL HAEMATOMA
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DIARRHOEA
         subjects affected / exposed
    0 / 83 (0.00%)
    6 / 167 (3.59%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    GASTROINTESTINAL HAEMORRHAGE
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    LARGE INTESTINE PERFORATION
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    NAUSEA
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    OESOPHAGEAL ULCER HAEMORRHAGE
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    RECTAL HAEMORRHAGE
         subjects affected / exposed
    1 / 83 (1.20%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SMALL INTESTINAL OBSTRUCTION
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    VOMITING
         subjects affected / exposed
    0 / 83 (0.00%)
    2 / 167 (1.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    CHOLECYSTITIS
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CHOLECYSTITIS ACUTE
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYPERBILIRUBINAEMIA
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    ANURIA
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CHRONIC KIDNEY DISEASE
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CYSTITIS HAEMORRHAGIC
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    OLIGURIA
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    RENAL FAILURE
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    ARTHRITIS
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    OSTEONECROSIS
         subjects affected / exposed
    1 / 83 (1.20%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PAIN IN EXTREMITY
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    ARTHRITIS INFECTIVE
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ASPERGILLUS INFECTION
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    BRONCHITIS
         subjects affected / exposed
    1 / 83 (1.20%)
    2 / 167 (1.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    BRONCHOPULMONARY ASPERGILLOSIS
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CELLULITIS
         subjects affected / exposed
    1 / 83 (1.20%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    LOWER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    1 / 83 (1.20%)
    3 / 167 (1.80%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    LUNG INFECTION
         subjects affected / exposed
    0 / 83 (0.00%)
    2 / 167 (1.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    MENINGITIS VIRAL
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    NEUTROPENIC SEPSIS
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    PNEUMONIA
         subjects affected / exposed
    3 / 83 (3.61%)
    6 / 167 (3.59%)
         occurrences causally related to treatment / all
    5 / 5
    3 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PNEUMONIA MORAXELLA
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PNEUMONIA STREPTOCOCCAL
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PSEUDOMEMBRANOUS COLITIS
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SEPTIC SHOCK
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    SINUSITIS
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SKIN INFECTION
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    STAPHYLOCOCCAL BACTERAEMIA
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    STAPHYLOCOCCAL SEPSIS
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    URINARY TRACT INFECTION
         subjects affected / exposed
    0 / 83 (0.00%)
    2 / 167 (1.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    UROSEPSIS
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    CACHEXIA
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    DEHYDRATION
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DIABETES MELLITUS
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYPERKALAEMIA
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYPOALBUMINAEMIA
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYPOPROTEINAEMIA
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Investigators Choice Lenalidomide
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    61 / 83 (73.49%)
    146 / 167 (87.43%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    TUMOUR FLARE
         subjects affected / exposed
    0 / 83 (0.00%)
    15 / 167 (8.98%)
         occurrences all number
    0
    17
    Vascular disorders
    HYPERTENSION
         subjects affected / exposed
    7 / 83 (8.43%)
    15 / 167 (8.98%)
         occurrences all number
    12
    18
    General disorders and administration site conditions
    ASTHENIA
         subjects affected / exposed
    11 / 83 (13.25%)
    26 / 167 (15.57%)
         occurrences all number
    16
    43
    FATIGUE
         subjects affected / exposed
    4 / 83 (4.82%)
    34 / 167 (20.36%)
         occurrences all number
    5
    45
    OEDEMA PERIPHERAL
         subjects affected / exposed
    9 / 83 (10.84%)
    16 / 167 (9.58%)
         occurrences all number
    10
    19
    PYREXIA
         subjects affected / exposed
    9 / 83 (10.84%)
    26 / 167 (15.57%)
         occurrences all number
    11
    44
    Respiratory, thoracic and mediastinal disorders
    COUGH
         subjects affected / exposed
    4 / 83 (4.82%)
    20 / 167 (11.98%)
         occurrences all number
    5
    29
    DYSPNOEA
         subjects affected / exposed
    6 / 83 (7.23%)
    10 / 167 (5.99%)
         occurrences all number
    7
    13
    Psychiatric disorders
    INSOMNIA
         subjects affected / exposed
    1 / 83 (1.20%)
    9 / 167 (5.39%)
         occurrences all number
    1
    17
    Investigations
    ALANINE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    5 / 83 (6.02%)
    8 / 167 (4.79%)
         occurrences all number
    8
    12
    Nervous system disorders
    HEADACHE
         subjects affected / exposed
    0 / 83 (0.00%)
    14 / 167 (8.38%)
         occurrences all number
    0
    23
    PARAESTHESIA
         subjects affected / exposed
    1 / 83 (1.20%)
    10 / 167 (5.99%)
         occurrences all number
    1
    10
    Blood and lymphatic system disorders
    ANAEMIA
         subjects affected / exposed
    18 / 83 (21.69%)
    45 / 167 (26.95%)
         occurrences all number
    41
    87
    LEUKOPENIA
         subjects affected / exposed
    18 / 83 (21.69%)
    29 / 167 (17.37%)
         occurrences all number
    57
    102
    LYMPHOPENIA
         subjects affected / exposed
    6 / 83 (7.23%)
    8 / 167 (4.79%)
         occurrences all number
    26
    19
    NEUTROPENIA
         subjects affected / exposed
    29 / 83 (34.94%)
    86 / 167 (51.50%)
         occurrences all number
    87
    446
    THROMBOCYTOPENIA
         subjects affected / exposed
    33 / 83 (39.76%)
    63 / 167 (37.72%)
         occurrences all number
    94
    194
    Ear and labyrinth disorders
    VERTIGO
         subjects affected / exposed
    0 / 83 (0.00%)
    9 / 167 (5.39%)
         occurrences all number
    0
    12
    Gastrointestinal disorders
    ABDOMINAL PAIN
         subjects affected / exposed
    4 / 83 (4.82%)
    16 / 167 (9.58%)
         occurrences all number
    5
    23
    ABDOMINAL PAIN UPPER
         subjects affected / exposed
    6 / 83 (7.23%)
    7 / 167 (4.19%)
         occurrences all number
    6
    8
    CONSTIPATION
         subjects affected / exposed
    5 / 83 (6.02%)
    29 / 167 (17.37%)
         occurrences all number
    7
    43
    DIARRHOEA
         subjects affected / exposed
    8 / 83 (9.64%)
    36 / 167 (21.56%)
         occurrences all number
    10
    104
    DYSPEPSIA
         subjects affected / exposed
    3 / 83 (3.61%)
    9 / 167 (5.39%)
         occurrences all number
    3
    10
    NAUSEA
         subjects affected / exposed
    13 / 83 (15.66%)
    17 / 167 (10.18%)
         occurrences all number
    19
    26
    VOMITING
         subjects affected / exposed
    9 / 83 (10.84%)
    8 / 167 (4.79%)
         occurrences all number
    9
    11
    Skin and subcutaneous tissue disorders
    DERMATITIS ALLERGIC
         subjects affected / exposed
    2 / 83 (2.41%)
    9 / 167 (5.39%)
         occurrences all number
    2
    15
    PRURITUS
         subjects affected / exposed
    3 / 83 (3.61%)
    15 / 167 (8.98%)
         occurrences all number
    3
    21
    RASH
         subjects affected / exposed
    3 / 83 (3.61%)
    19 / 167 (11.38%)
         occurrences all number
    3
    31
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA
         subjects affected / exposed
    2 / 83 (2.41%)
    12 / 167 (7.19%)
         occurrences all number
    2
    14
    BACK PAIN
         subjects affected / exposed
    0 / 83 (0.00%)
    16 / 167 (9.58%)
         occurrences all number
    0
    26
    MUSCLE SPASMS
         subjects affected / exposed
    3 / 83 (3.61%)
    13 / 167 (7.78%)
         occurrences all number
    4
    16
    PAIN IN EXTREMITY
         subjects affected / exposed
    0 / 83 (0.00%)
    13 / 167 (7.78%)
         occurrences all number
    0
    21
    Infections and infestations
    BRONCHITIS
         subjects affected / exposed
    8 / 83 (9.64%)
    15 / 167 (8.98%)
         occurrences all number
    11
    22
    CONJUNCTIVITIS
         subjects affected / exposed
    0 / 83 (0.00%)
    9 / 167 (5.39%)
         occurrences all number
    0
    11
    INFLUENZA
         subjects affected / exposed
    1 / 83 (1.20%)
    9 / 167 (5.39%)
         occurrences all number
    3
    10
    NASOPHARYNGITIS
         subjects affected / exposed
    5 / 83 (6.02%)
    25 / 167 (14.97%)
         occurrences all number
    5
    39
    RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    0 / 83 (0.00%)
    10 / 167 (5.99%)
         occurrences all number
    0
    20
    UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    5 / 83 (6.02%)
    23 / 167 (13.77%)
         occurrences all number
    11
    51
    Metabolism and nutrition disorders
    DECREASED APPETITE
         subjects affected / exposed
    3 / 83 (3.61%)
    22 / 167 (13.17%)
         occurrences all number
    4
    31
    HYPOALBUMINAEMIA
         subjects affected / exposed
    1 / 83 (1.20%)
    9 / 167 (5.39%)
         occurrences all number
    1
    11
    HYPOKALAEMIA
         subjects affected / exposed
    1 / 83 (1.20%)
    15 / 167 (8.98%)
         occurrences all number
    1
    22

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    21 Apr 2009
    Eligibility criteria were updated. The exclusion criteria for corticosteroids, allowed for subjects to have prednisone ≤ 10 mg/day for purposes other than MCL. Expanded enrollment to those who received prior radiotherapy or experimental IP. Confirmation of MCL diagnosis by Central Pathology (CP) not required. Updated the timeline/tumor biopsy required for CP to confirm MCL at screening and for other assessments. Analysis of t(11;14)(q13;q32) translocation by FISH was optional. Bone marrow (BM) biopsy at screening was recommended to: 1)confirm diagnosis 2)confirm or rule out MCL BM infiltration 3)justify thrombocytopenia in screened subjects 4)gain additional tissue for the biomarker substudy. Changed the time between randomization and IP initiation to 4 days. Added 2 pregnancy tests for FCBP before starting IP. Updated dose modification for thromboembolic prophylaxis. Provided guidance on medical management of TLS for those developing LTLS or Grade ≥ 1 TLS. Updated dose modification rules for Len; included dose adjustments for neurological and liver toxicities. Limited prophylaxis for thromboembolism only to Len-treated subjects at high risk. Updated response criteria: BM required for confirmation of CR; marrow not needed. Revised treatment cycle duration. Limited the maximum duration between the Control Arm for those initiating crossover IP and subsequent Len to 10 weeks. Updated use of growth factors for severe hematologic events. Rituxan treated subjects could receive corticosteroids for prevention of cytokine release syndrome. Added QoL time points. Exploratory objectives regarding correlative biology investigation were updated; included investigation of potential predictive and PD parameter by analysis of biomarkers in archival and collected biopsy samples from tumor, blood & plasma. The 28 days wash out period required for blood, semen or sperm donation was added. Coagulation and chloride tests were deleted.
    14 Dec 2009
    The primary objective was changed from determine the ORR to compare the PFS, since PFS was a clinically relevant efficacy endpoint and acceptable endpoint for a registration trial. The ORR was defined as a secondary objective. Study design, study endpoints, analysis methods, interim analysis, sample size, and power considerations were updated. Sample size calculation was revised. Statistical test for the secondary endpoints was added to reflect the change in the nature of the study. Futility analyses were to be conducted by the DMC when approximately 80 subjects completed 2 cycles or withdrew before having 2 cycles. Eligibility criteria update: The limitation to the number of prior treatment lines was changed to number of prior relapses and was no longer limited to chemotherapy. DVT prophylaxis was no longer required for those at risk. The criterion was updated to match the Section Treatment Assignments, Thromboembolism, of the Study Protocol. A mandatory 7-day wash-out period was required for prior corticosteroid use. The upper limit of abnormal liver values were updated:the planned modification of len doses in case of toxicity. Enrollment was allowed with AST/SGOT or ALT/SGPT ≥ 3.0 x ULN (unless documented liver involvement by lymphoma). Total bilirubin > 1.5 mg/dL (except in case of Gilbert’s syndrome and documented liver involvement by lymphoma) was required instead of the previous limit > 1.5 x mg/dL bilirubin (except in case of hemolytic anemia). Explorative objectives were focused on blood samples and archival/re-biopsy tumor specimens. The serial fresh lymph nodes biopsies were deleted. Clarification: participation in the biomarker substudy was optional and the sampling pertained to those who provided additional consent. Clarification: the preferred imaging method was CT, and MRI was to be used if CT was contraindicated. The guidance for toxicity management was updated to clarify: recommendations for TFR and TLS were mainly for those receiving len.
    29 Apr 2011
    Added SPMs and were regarded as SAEs and reported throughout the study, including from the time of signing the ICF through follow-up for OS. Changes to the planned protocol analysis of SPMs are in Section 9.8.2.2. A study duration item, “4 years from last subject randomized”, was added to the end-of-study definition. Requirements for consent withdrawal from treatment, efficacy, and survival follow-up and allowing collection of follow-up data until study closure were clarified. A full consent withdrawal had to be documented to disallow survival follow-up. Statistical analysis was updated to include the stratified log-rank test for the main comparison, changed unstratified log-rank test to be used as supportive analysis, and added the statement that any demographic or baseline characteristics variables considered as strong predictive or prognostic factors were included as part of the SAP. The interim analysis section was updated to include the option of providing the DMC with additional data upon request. Updated the dose modification requirements as follows: specified that for len, a minimum 7-day rest period was mandatory before starting a new treatment cycle; this period had to be adhered to regardless of allowed visit windows. Updated the dose modifications and interruptions for len to include “Action required” for any other len-related AE not requiring IP discontinuation. Updated the dose reductions for len to replace the 10-mg every-other-day dose level with 5-mg every-day-dose. Changes to the planned protocol analysis of SPMs were in Section 9.8.2.2. A study duration item, “4 years from last subject randomized”, was added to the end-of-study definition. Requirements for consent withdrawal from treatment, efficacy, and survival follow-up was added allowing collection of follow-up data until study closure were clarified. For subjects in the Follow-up Phase who withdrew consent for efficacy (disease progression), the follow-up continued for survival.
    27 Sep 2011
    Based on the recommendation from the third DMC held on 22 Jul 2011, the following changes were implemented: sample size was increased from 167 to 250 subjects. The sample size increase was implemented to allow a reliable estimation of potential PFS differences between the study arms. According to the DMC, the outcome observed in the Control Arm of the study was different from the initial assumptions used to calculate the sample size. The primary efficacy analysis was set 1 year after the last subject was randomized. Efficacy subgroup analyses were added to investigate the treatment effect in different subgroups or subpopulation in an exploratory manner. The changes in statistical analyses are detailed in Section 9.8.2.2. The MIPI score at baseline was added to the list of treatment and clinical characteristics. The change was implemented because the DMC had observed an imbalance in terms of risk factors between the arms, which was not mitigated by the stratification factors and, thus, recommended to include the MIPI at baseline in the stratified test (Section 9.8.2.2). Exploratory analyses were planned on the AT Population for the following endpoints: PFS, ORR, and OS. Added a fourth safety analysis after 200 subjects completed 2 cycles or withdrew before completing 2 cycles. The addition was implemented to ensure safety monitoring according to the sample size increase to 250 subjects. Added a fourth EORTC QoL compliance assessment after 200 subjects completed 2 cycles or withdrew before completing 2 cycles. This addition was implemented to ensure ongoing monitoring of EORTC QoL compliance according to the sample size increase to 250 subjects. Extended the duration of prior malignancy-free history required for enrollment (from ≥ 3 to ≥ 5 years). This modification was implemented as requested by Health Authorities to reduce the risk of SPM in subjects treated with lenalidomide. Discontinued further biomarker analysis on blood and plasma samples in the study.
    22 Mar 2013
    Thromboembolic prophylaxis had to be given to all subjects treated with lenalidomide regardless of prior thromboembolic history, instead of only to subjects at high risk of TEs. This modification was implemented following a DMC recommendation for mandatory prophylaxis of study subjects on lenalidomide because the DMC had observed an increase in TEs in the Lenalidomide Arm compared to the Control Arm and because a number of the subjects with TEs were not receiving anti-thromboembolic prophylaxis.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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