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    Clinical Trial Results:
    A Phase 2, Multicenter, International, Single Arm Study to Assess the Safety and Efficacy of Single Agent CC-486 (Oral Azacitidine) in Previously Treated Subjects With Locally Advanced or Metastatic Nasopharyngeal Carcinoma

    Summary
    EudraCT number
    		 2014-001745-25
    Trial protocol
    		 ES   GR   IT  
    Global end of trial date
    20 Apr 2017

    Results information
    Results version number
    		 v2(current)
    This version publication date
    14 Jun 2018
    First version publication date
    02 May 2018
    Other versions
    		 v1
    Version creation reason
    • Correction of full data set
    One of the Baseline Characteristics unit type was corrected.

    Trial information

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    Trial identification
    Sponsor protocol code
    CC-486-NPC-001
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02269943
    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
    Ileana Elias, MD, Celgene Corporation, 01 647-968-4300, Ilelias@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
    08 Aug 2017
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    20 Apr 2017
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To evaluate the efficacy of CC-486 in subjects with nasopharyngeal carcinoma (NPC)
    Protection of trial subjects
    Patient Confidentiality, Personal Data Protection and Pharmacokinetic Consent; this study was conducted in accordance with the guidelines of current Good Clinical Practice including the archiving of essential documents.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    13 Feb 2015
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Efficacy
    Long term follow-up duration
    		 28 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United States: 2
    Country: Number of subjects enrolled
    Canada: 1
    Country: Number of subjects enrolled
    Singapore: 4
    Country: Number of subjects enrolled
    Taiwan: 6
    Country: Number of subjects enrolled
    Greece: 4
    Country: Number of subjects enrolled
    Italy: 7
    Country: Number of subjects enrolled
    Tunisia: 1
    Country: Number of subjects enrolled
    France: 4
    Country: Number of subjects enrolled
    Spain: 7
    Worldwide total number of subjects
    36
    EEA total number of subjects
    22
    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)
    29
    From 65 to 84 years
    7
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 This was a multicenter study with 17 sites from the United States, Canada, France. Greece, Italy, Spain, Taiwan, Singapore and Tunisia.

    Pre-assignment
    Screening details
    		 Participants were enrolled according to a Simon 2-stage design. The first 6 participants of Asian-Pacific Island ethnicity received 200 mg/day CC-486 on days 1-14 of each 21-day cycle to monitor safety and tolerability; if there were no safety concerns, subsequent participants of Asian-Pacific Island ethnicity would receive the 300 mg daily dose

    Period 1
    Period 1 title
    Treatment Period (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 CC-486 200 mg
    Arm description
    		 Asian-Pacific island participants received CC-486 200 mg tablets by mouth (PO) on days 1-14 of each 21-day cycle until radiologic disease progression, unacceptable toxicity, adverse event, a new anticancer therapy is begun, withdrawal of consent, subject refusal, physician decision, or death. If well tolerated, and there were no safety concerns, subsequent participants of Asian-Pacific Island ethnicity were administered CC-486 300-mg PO daily for 14 days of a 21-day cycle. Subjects completed the study in accordance with protocol guidelines.
    Arm type
    		 Experimental

    Investigational medicinal product name
    CC-486
    Investigational medicinal product code
    Other name
    Oral Azacitidine
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    CC-486 200 mg tablets on Days 1-14 of each 21-day treatment cycle

    Arm title
    		 CC-486 300 mg
    Arm description
    		 Participants received CC-486 300 mg tablets by mouth on days 1-14 of each 21-day cycle until radiologic disease progression, unacceptable toxicity, adverse event (AE), a new anticancer therapy is begun, withdrawal of consent, subject refusal, physician decision, or death. Subjects completed the study in accordance with protocol guidelines.
    Arm type
    		 Experimental

    Investigational medicinal product name
    CC-486
    Investigational medicinal product code
    Other name
    Oral Azacitidine
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    CC-486 300 mg tablets on Days 1 to 14 of each 21-day treatment cycle

    Number of subjects in period 1
    		CC-486 200 mg CC-486 300 mg
    Started
    6
    30
    Study Drug Discontinued
    6
    30
    Completed
    0
    0
    Not completed
    6
    30
         Adverse event, serious fatal
    -
    1
         Adverse event, non-fatal
    1
    10
         Progressive Disease
    5
    17
         Symptomatic Deterioration
    -
    2

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    CC-486 200 mg
    Reporting group description
    		 Asian-Pacific island participants received CC-486 200 mg tablets by mouth (PO) on days 1-14 of each 21-day cycle until radiologic disease progression, unacceptable toxicity, adverse event, a new anticancer therapy is begun, withdrawal of consent, subject refusal, physician decision, or death. If well tolerated, and there were no safety concerns, subsequent participants of Asian-Pacific Island ethnicity were administered CC-486 300-mg PO daily for 14 days of a 21-day cycle. Subjects completed the study in accordance with protocol guidelines.

    Reporting group title
    CC-486 300 mg
    Reporting group description
    		 Participants received CC-486 300 mg tablets by mouth on days 1-14 of each 21-day cycle until radiologic disease progression, unacceptable toxicity, adverse event (AE), a new anticancer therapy is begun, withdrawal of consent, subject refusal, physician decision, or death. Subjects completed the study in accordance with protocol guidelines.

    Reporting group values
    		 CC-486 200 mg CC-486 300 mg Total
    Number of subjects
    		 6 30 36
    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)
    		 4 25 29
        From 65-84 years
    		 2 5 7
        85 years and over
    		 0 0 0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 53.2 ( 11.70 ) 52.2 ( 11.60 ) -
    Sex: Female, Male
    Units: Subjects
        Female
    		 2 5 7
        Male
    		 4 25 29
    Race/Ethnicity, Customized
    Units: Subjects
        Asian|
    		 6 7 13
        White|
    		 0 23 23
    Race/Ethnicity, Customized
    Units: Subjects
        Hispanic|
    		 0 0 0
        Non-Hispanic or Latino|
    		 6 30 36
    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 (Most Favorable Activity); 1 = Restricted activity but ambulatory; 2 = Ambulatory but unable to carry out work activities; 3 = Limited Self-Care; 4 = Completely Disabled, No self-care (Least Favorable Activity)
    Units: Subjects
        0 = Fully Active|
    		 4 11 15
        1 = Restrictive but ambulatory|
    		 2 18 20
        2 = Ambulatory but unable to work|
    		 0 1 1
        3 = Limited Self-Care|
    		 0 0 0
    Nasopharyngeal Cancer (NPC) Diagnosis Types
    The 3 types of NPC, based on how the cancer cells look under the microscope include: 1. Undifferentiated Nasopharyngeal Carcinoma 2. Poorly Differentiated Nasopharyngeal Carcinoma 3. Other
    Units: Subjects
        Undifferentiated Nasopharyngeal Carcinoma|
    		 2 21 23
        Poorly Differentiated Nasopharyngeal Carcinoma|
    		 2 9 11
        Other|
    		 2 0 2
    Participants with Prior Anti-Cancer Therapies
    Units: Subjects
        Prior Systemic Anticancer Therapy
    		 6 29 35
        No Prior Anticancer Therapy
    		 0 1 1
    Time From Initial Diagnosis to First Dose
    Units: years
        arithmetic mean (standard deviation)
    		 3.60 ( 3.204 ) 3.86 ( 3.358 ) -

    End points

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    End points reporting groups
    Reporting group title
    CC-486 200 mg
    Reporting group description
    		 Asian-Pacific island participants received CC-486 200 mg tablets by mouth (PO) on days 1-14 of each 21-day cycle until radiologic disease progression, unacceptable toxicity, adverse event, a new anticancer therapy is begun, withdrawal of consent, subject refusal, physician decision, or death. If well tolerated, and there were no safety concerns, subsequent participants of Asian-Pacific Island ethnicity were administered CC-486 300-mg PO daily for 14 days of a 21-day cycle. Subjects completed the study in accordance with protocol guidelines.

    Reporting group title
    CC-486 300 mg
    Reporting group description
    		 Participants received CC-486 300 mg tablets by mouth on days 1-14 of each 21-day cycle until radiologic disease progression, unacceptable toxicity, adverse event (AE), a new anticancer therapy is begun, withdrawal of consent, subject refusal, physician decision, or death. Subjects completed the study in accordance with protocol guidelines.

    Primary: Percentage of Participants who Achieved a Complete or Partial Response According to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) Based on an Independent Radiology Assessment (IRA)

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    End point title
    		 Percentage of Participants who Achieved a Complete or Partial Response According to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) Based on an Independent Radiology Assessment (IRA) [1]
    End point description
    Overall response rate was defined as the percentage of participants with a Complete Response (CR) or Partial Response (PR), confirmed no less than 4 weeks after the criteria for response were first met, based on independent radiology assessment according to RECIST 1.1 criteria. Complete response was defined as the disappearance of all target lesions and non-target lesions; Partial response is at least a 30% decrease from baseline in the sum of diameters of target lesions with no progression of non-target lesions and no new lesions or disappearance of target lesions with persistence of one or more non-target lesions from baseline. The Efficacy Evaluable Population (EEP) included all enrolled participants who met eligibility criteria and either received 2 cycles of CC-486 at any dose and discontinued treatment for progressive disease (PD) or received 4 cycles of CC-486 and had a baseline and at least 2 post-screening tumor assessments.
    End point type
    Primary
    End point timeframe
    Tumor response was assessed every (Q) 6 weeks for the first 3 evaluations then Q 9 weeks until disease progression. As of the cut-off date of 08 August 2017; the median duration of treatment was 257 days for the 200 mg dose and 114.5 days for 300 mg dose
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Since this is an open-label, single arm study with limited sample size, treatment comparisons are not applicable. Therefore no formal statistical analyses were conducted.
    End point values
    		 CC-486 200 mg CC-486 300 mg
    Number of subjects analysed
    5 [2]
    20
    Units: percentage of participants
        number (confidence interval 90%)
    0 (-99999 to 99999)
    15.0 (4.2 to 34.4)
    Notes
    [2] - 99999 = Confidence Interval (CI) could not be calculated due to zero subjects with a response.
    No statistical analyses for this end point

    Primary: Kaplan Meier Estimate of Progression-Free Survival (PFS) Based on an Independent Radiology Assessment According to RECIST 1.1 Criteria

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    End point title
    		 Kaplan Meier Estimate of Progression-Free Survival (PFS) Based on an Independent Radiology Assessment According to RECIST 1.1 Criteria [3]
    End point description
    PFS was defined as the time from the first day of the study treatment to the date of disease progression or death (any cause) on or prior to the data cut-off date for the statistical analysis, whichever occurred earlier, based on an independent radiology assessment of response using RECIST v1.1 criteria. Progressive disease was defined as at least a 20% increase in the sum of diameters of target or non-target lesions from nadir or appearance of a new lesion. The Efficacy Evaluable Population included all enrolled participants who met eligibility criteria and either received 2 cycles of CC-486 at any dose and discontinued treatment for progressive disease or received 4 cycles of CC-486 and had a baseline and at least 2 post-screening tumor assessments.
    End point type
    Primary
    End point timeframe
    From Day 1 of study drug up to the data cut off date of 08 August 2017; median follow-up time for censored participants was 12.3 months
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Since this is an open-label, single arm study with limited sample size, treatment comparisons are not applicable. Therefore no formal statistical analyses were conducted.
    End point values
    		 CC-486 200 mg CC-486 300 mg
    Number of subjects analysed
    5 [4]
    20
    Units: months
        median (confidence interval 90%)
    6.2 (1.4 to 99999)
    4.4 (1.6 to 7.3)
    Notes
    [4] - 99999 = Upper limit of the confidence interval (CI) was not reached due to limited number of events
    No statistical analyses for this end point

    Secondary: Kaplan Meier Estimate of Overall Survival

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    End point title
    		 Kaplan Meier Estimate of Overall Survival
    End point description
    Overall survival was the time from the first dose of study drug to patient death from any cause. Participants who did not die were censored at the last known time the patient was alive date or the clinical data cutoff date, whichever was earlier. The Efficacy Evaluable Population included all enrolled participants who met eligibility criteria and either received 2 cycles of CC-486 at any dose and discontinued treatment for progressive disease or received 4 cycles of CC-486 and had a baseline and at least 2 post-screening tumor assessments.
    End point type
    Secondary
    End point timeframe
    From Day 1 of study treatment to the first date of progressive disease or death; up to data cut-off date of 08 August 2017; overall median follow-up time for censored participants was 20.4 months
    End point values
    		 CC-486 200 mg CC-486 300 mg
    Number of subjects analysed
    5 [5]
    20 [6]
    Units: months
        median (confidence interval 90%)
    18.0 (15.9 to 99999)
    99999 (12.5 to 999999)
    Notes
    [5] - 99999 = The upper limit of the CI for PFS could not be calculated due to limited number of events
    [6] - 99999= The median and upper limits of the CI could not be calculated due to limited number of events
    No statistical analyses for this end point

    Secondary: Percentage of Participants with Stable Disease for ≥ 16 Weeks from the Date of the First Treatment, or CR or PR According to RECIST 1.1 Criteria and Based on an Independent Radiology Assessment

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    End point title
    		 Percentage of Participants with Stable Disease for ≥ 16 Weeks from the Date of the First Treatment, or CR or PR According to RECIST 1.1 Criteria and Based on an Independent Radiology Assessment
    End point description
    Disease Control Rate (DCR) was defined as the percentage of participants with a CR, PR, confirmed ≥ 4 weeks after the criteria for response were first met or stable disease for ≥ 16 weeks from the first treatment, based on IRA using RECIST 1.1 criteria. A complete response was defined as the disappearance of all target lesions and non-target lesions; a partial response was defined as at least a 30% decrease from baseline in the sum of diameters of target lesions with no progression of non-target lesions and no new lesions or disappearance of target lesions with persistence of one or more non-target lesions from baseline; stable disease was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase of lesions to qualify for PD. The EEP = all enrolled participants who met eligibility and either received 2 cycles of CC-486 at any dose and discontinued CC-486 for PD or received 4 cycles of CC-486 and had a baseline and at least 2 post-screening tumor assessments.
    End point type
    Secondary
    End point timeframe
    Tumor response was assessed every 6 weeks for the first 3 evaluations then every 9 weeks until disease progression. As of the cut-off date of 08 August 2017 the median duration of treatment was 257 days for the 200 mg dose and 114.5 days for 300 mg dose
    End point values
    		 CC-486 200 mg CC-486 300 mg
    Number of subjects analysed
    5
    20
    Units: percentage of participants
        median (confidence interval 90%)
    60.0 (18.9 to 92.4)
    50.0 (30.2 to 69.8)
    No statistical analyses for this end point

    Secondary: Number of Participants with Treatment Emergent Adverse Events

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    End point title
    		 Number of Participants with Treatment Emergent Adverse Events
    End point description
    Treatment-emergent adverse events (TEAEs) were defined as any adverse event (AE) or serious adverse event (SAE) that occurred or worsened on or after the day of the first dose of the investigational product (IP) through 28 days after the last dose of IP. In addition, any SAE with an onset date more than 28 day after the last dose of IP that was assessed by the investigator as related to IP was considered a TEAE. The severity of AEs was graded based on National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0 and based on the following scale: Grade 1 = Mild Grade 2 = Moderate Grade 3 = Severe Grade 4 = Life threatening Grade 5 = Death.
    End point type
    Secondary
    End point timeframe
    From date of first dose of study treatment to 28 days after last dose of study treatment; up to final data cut-off date of 08 August 2017; median treatment duration was 257 days for CC-486 200 mg and 114.5 days for CC-486 300 mg
    End point values
    		 CC-486 200 mg CC-486 300 mg
    Number of subjects analysed
    6
    30
    Units: Participants
        Any TEAE|
    6
    30
        Any TEAE Related to IP|
    6
    28
        Any Serious TEAE|
    4
    12
        Any Serious TEAE Related to IP|
    3
    7
        Any CTCAE Grade 3 or 4 TEAE|
    6
    20
        Any CTCAE Grade 3 or 4 TEAE Related to IP|
    6
    16
        Any TEAE Leading to Death|
    1
    1
        Any TEAE Leading to Dose Reduction|
    5
    9
        Any TEAE Leading to Drug Interruption|
    4
    9
        Any TEAE Leading to IP Discontinuation|
    1
    10
    No statistical analyses for this end point

    Secondary: Area Under the Plasma Concentration-time Curve from Time 0 to the Time of the Last Quantifiable Concentration Of CC-486 (AUC-t)

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    End point title
    		 Area Under the Plasma Concentration-time Curve from Time 0 to the Time of the Last Quantifiable Concentration Of CC-486 (AUC-t)
    End point description
    Area under the plasma concentration-time curve from Time 0 to the time of the last quantifiable concentration, calculated by linear trapezoidal method when concentrations are increasing and the logarithmic trapezoidal method when concentrations are decreasing. The PK population includes participants with evaluable CC-486 plasma PK profiles.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 and Cycle 1 Day 14
    End point values
    		 CC-486 200 mg CC-486 300 mg
    Number of subjects analysed
    6
    30
    Units: ng*h/mL
    geometric mean (geometric coefficient of variation)
        Cycle 1 Day 1|
    390.0 ( 58.8 )
    351.7 ( 87.5 )
        Cycle 1 Day 14|
    130.3 ( 995.5 )
    461.3 ( 104.2 )
    No statistical analyses for this end point

    Secondary: Area Under the Plasma Concentration -Time Curve from 0 Extrapolated to Infinity (AUC-inf, AUC0-∞) Of CC-486

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    End point title
    		 Area Under the Plasma Concentration -Time Curve from 0 Extrapolated to Infinity (AUC-inf, AUC0-∞) Of CC-486
    End point description
    Area under the plasma concentration-time curve from Time 0 extrapolated to infinity, calculated as [AUCt + Ct/ λz]. Ct is the last quantifiable concentration. No AUC extrapolation was performed with unreliable λz. If AUC %Extrap was ≥25%, AUC inf was not reported. The PK population includes participants with evaluable CC-486 plasma PK profiles.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 and Cycle 1 Day 14
    End point values
    		 CC-486 200 mg CC-486 300 mg
    Number of subjects analysed
    6
    30
    Units: ng*h/mL
    geometric mean (geometric coefficient of variation)
        Cycle 1 Day 1|
    392.5 ( 58.3 )
    354.9 ( 87.1 )
        Cycle 1 Day 14|
    138.0 ( 802.1 )
    466.0 ( 104.7 )
    No statistical analyses for this end point

    Secondary: Maximum Observed Concentration (Cmax) Of CC-486

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    End point title
    		 Maximum Observed Concentration (Cmax) Of CC-486
    End point description
    Maximum observed plasma concentration, obtained directly from the observed concentration versus time data. The PK population includes participants with evaluable CC-486 plasma PK profiles.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 and Cycle 1 Day 14
    End point values
    		 CC-486 200 mg CC-486 300 mg
    Number of subjects analysed
    6
    30
    Units: ng/mL
    geometric mean (geometric coefficient of variation)
        Cycle 1 Day 1|
    266.3 ( 53.8 )
    170.7 ( 95.0 )
        Cycle 1 Day 14|
    102.7 ( 412.0 )
    287.0 ( 50.7 )
    No statistical analyses for this end point

    Secondary: Time to Reach Maximum Concentration (Tmax) Of CC-486

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    End point title
    		 Time to Reach Maximum Concentration (Tmax) Of CC-486
    End point description
    Time to Cmax, obtained directly from the observed concentration versus time data. The PK population includes participants with evaluable CC-486 plasma PK profiles.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 and Cycle 1 Day 14
    End point values
    		 CC-486 200 mg CC-486 300 mg
    Number of subjects analysed
    6
    30
    Units: Hours
    median (full range (min-max))
        Cycle 1 Day 1|
    1.0 (0.50 to 1.5)
    1.3 (0.50 to 1.5)
        Cycle 1 Day 14|
    1.0 (0.0 to 2.0)
    1.0 (0.50 to 3.0)
    No statistical analyses for this end point

    Secondary: Terminal Half-Life (t1/2) of CC-486

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    End point title
    		 Terminal Half-Life (t1/2) of CC-486
    End point description
    Terminal phase half-life in plasma, calculated as [(ln 2)/λz]. t1/2 was only calculated when a reliable estimate for λz could be obtained. The PK population includes participants with evaluable CC-486 plasma PK profiles.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 and Cycle 1 Day 14
    End point values
    		 CC-486 200 mg CC-486 300 mg
    Number of subjects analysed
    6
    30
    Units: Hours
    geometric mean (geometric coefficient of variation)
        Cycle 1 Day 1|
    0.562 ( 23.1 )
    0.635 ( 24.2 )
        Cycle 1 Day 14|
    0.584 ( 17.2 )
    0.640 ( 32.0 )
    No statistical analyses for this end point

    Secondary: Apparent Total Clearance (CL/F) Of CC-486

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    End point title
    		 Apparent Total Clearance (CL/F) Of CC-486
    End point description
    Apparent volume of distribution, calculated as [(CL/F)/λz]. The PK population includes participants with evaluable CC-486 plasma PK profiles.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 and Cycle 1 Day 14
    End point values
    		 CC-486 200 mg CC-486 300 mg
    Number of subjects analysed
    6
    30
    Units: Liters/hour
    geometric mean (geometric coefficient of variation)
        Cycle 1 Day 1|
    509.5 ( 58.3 )
    845.3 ( 87.1 )
        Cycle 1 Day 14|
    1450 ( 802.1 )
    643.7 ( 104.7 )
    No statistical analyses for this end point

    Secondary: Apparent Volume of Distribution (Vz/F) Of CC-486

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    End point title
    		 Apparent Volume of Distribution (Vz/F) Of CC-486
    End point description
    Apparent volume of distribution, calculated as [(CL/F)/λz]. The PK population includes participants with evaluable CC-486 plasma PK profiles.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 and Cycle 1 Day 14
    End point values
    		 CC-486 200 mg CC-486 300 mg
    Number of subjects analysed
    6
    30
    Units: Liters
    geometric mean (geometric coefficient of variation)
        Cycle 1 Day 1|
    412.9 ( 42.9 )
    774.6 ( 78.6 )
        Cycle 1 Day 14|
    1221 ( 581.3 )
    594.8 ( 69.7 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From Day 1 of CC-486 until 28 days after the last dose and those SAEs made known to the Investigator at any time thereafter that are suspected of being related to CC-486; up to final cut-off date of 08 August 2017
    Adverse event reporting additional description
    Median duration of study treatment was 257 days for CC-486 200 mg and 114.5 days for CC-486 300 mg
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.0
    Reporting groups
    Reporting group title
    CC-486 300 mg
    Reporting group description
    		 Participants received CC-486 300 mg tablets by mouth on days 1-14 of each 21-day cycle until radiologic disease progression, unacceptable toxicity, adverse event (AE), a new anticancer therapy is begun, withdrawal of consent, subject refusal, physician decision, or death.

    Reporting group title
    CC-486 200 mg
    Reporting group description
    		 Asian-Pacific island participants received CC-486 200 mg tablets by mouth (PO) on days 1-14 of each 21-day cycle until radiologic disease progression, unacceptable toxicity, adverse event, a new anticancer therapy is begun, withdrawal of consent, subject refusal, physician decision, or death. If well tolerated, and there were no safety concerns, subsequent participants of Asian-Pacific Island ethnicity were administered CC-486 300-mg PO daily for 14 days of a 21-day cycle

    Serious adverse events
    		 CC-486 300 mg CC-486 200 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    12 / 30 (40.00%)
    4 / 6 (66.67%)
         number of deaths (all causes)
    18
    4
         number of deaths resulting from adverse events
    0
    Investigations
    Neutrophil count decreased
         subjects affected / exposed
    0 / 30 (0.00%)
    2 / 6 (33.33%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Tracheo-oesophageal fistula
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Brain oedema
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    1 / 30 (3.33%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoaesthesia
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Febrile neutropenia
         subjects affected / exposed
    2 / 30 (6.67%)
    2 / 6 (33.33%)
         occurrences causally related to treatment / all
    2 / 2
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 30 (3.33%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Cataract
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Dysphagia
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Epistaxis
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Musculoskeletal and connective tissue disorders
    Muscular weakness
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Septic shock
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Pneumonia
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hypernatraemia
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 CC-486 300 mg CC-486 200 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    29 / 30 (96.67%)
    6 / 6 (100.00%)
    Vascular disorders
    Hypotension
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    General disorders and administration site conditions
    Face oedema
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    Asthenia
         subjects affected / exposed
    8 / 30 (26.67%)
    0 / 6 (0.00%)
         occurrences all number
    20
    0
    Facial pain
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    Fatigue
         subjects affected / exposed
    5 / 30 (16.67%)
    3 / 6 (50.00%)
         occurrences all number
    10
    3
    Hypothermia
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    3
    Non-cardiac chest pain
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 6 (0.00%)
         occurrences all number
    3
    0
    Oedema peripheral
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    Pyrexia
         subjects affected / exposed
    8 / 30 (26.67%)
    1 / 6 (16.67%)
         occurrences all number
    11
    2
    Reproductive system and breast disorders
    Menstrual disorder
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Dysphonia
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    Cough
         subjects affected / exposed
    6 / 30 (20.00%)
    1 / 6 (16.67%)
         occurrences all number
    7
    1
    Nasal congestion
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    Pleural effusion
         subjects affected / exposed
    1 / 30 (3.33%)
    1 / 6 (16.67%)
         occurrences all number
    1
    1
    Rhinorrhoea
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    Productive cough
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    3
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    2 / 30 (6.67%)
    1 / 6 (16.67%)
         occurrences all number
    2
    1
    Anxiety
         subjects affected / exposed
    3 / 30 (10.00%)
    1 / 6 (16.67%)
         occurrences all number
    3
    1
    Investigations
    Aspartate aminotransferase increased
         subjects affected / exposed
    2 / 30 (6.67%)
    1 / 6 (16.67%)
         occurrences all number
    7
    1
    Alanine aminotransferase increased
         subjects affected / exposed
    5 / 30 (16.67%)
    1 / 6 (16.67%)
         occurrences all number
    15
    1
    Blood alkaline phosphatase increased
         subjects affected / exposed
    2 / 30 (6.67%)
    1 / 6 (16.67%)
         occurrences all number
    2
    1
    Blood creatinine increased
         subjects affected / exposed
    1 / 30 (3.33%)
    1 / 6 (16.67%)
         occurrences all number
    1
    2
    C-reactive protein increased
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    Neutrophil count decreased
         subjects affected / exposed
    1 / 30 (3.33%)
    1 / 6 (16.67%)
         occurrences all number
    1
    2
    Weight decreased
         subjects affected / exposed
    5 / 30 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    10
    0
    Injury, poisoning and procedural complications
    Humerus fracture
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    Cardiac disorders
    Sinus tachycardia
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    Nervous system disorders
    Dysgeusia
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    Dizziness
         subjects affected / exposed
    3 / 30 (10.00%)
    1 / 6 (16.67%)
         occurrences all number
    4
    1
    Facial paralysis
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    Hypoaesthesia
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    Headache
         subjects affected / exposed
    2 / 30 (6.67%)
    1 / 6 (16.67%)
         occurrences all number
    2
    1
    Neuropathy peripheral
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    Syncope
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    5 / 30 (16.67%)
    1 / 6 (16.67%)
         occurrences all number
    10
    3
    Leukopenia
         subjects affected / exposed
    4 / 30 (13.33%)
    0 / 6 (0.00%)
         occurrences all number
    9
    0
    Neutropenia
         subjects affected / exposed
    9 / 30 (30.00%)
    3 / 6 (50.00%)
         occurrences all number
    24
    12
    Thrombocytopenia
         subjects affected / exposed
    3 / 30 (10.00%)
    1 / 6 (16.67%)
         occurrences all number
    9
    2
    Ear and labyrinth disorders
    Deafness unilateral
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    Ear pain
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 6 (0.00%)
         occurrences all number
    3
    0
    Eye disorders
    Eye oedema
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 30 (3.33%)
    1 / 6 (16.67%)
         occurrences all number
    1
    1
    Abdominal distension
         subjects affected / exposed
    1 / 30 (3.33%)
    1 / 6 (16.67%)
         occurrences all number
    1
    2
    Constipation
         subjects affected / exposed
    10 / 30 (33.33%)
    1 / 6 (16.67%)
         occurrences all number
    18
    1
    Abdominal pain upper
         subjects affected / exposed
    3 / 30 (10.00%)
    1 / 6 (16.67%)
         occurrences all number
    3
    1
    Dental caries
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    Diarrhoea
         subjects affected / exposed
    10 / 30 (33.33%)
    3 / 6 (50.00%)
         occurrences all number
    17
    6
    Dyspepsia
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    Dysphagia
         subjects affected / exposed
    4 / 30 (13.33%)
    0 / 6 (0.00%)
         occurrences all number
    4
    0
    Inguinal hernia
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    Nausea
         subjects affected / exposed
    18 / 30 (60.00%)
    6 / 6 (100.00%)
         occurrences all number
    36
    9
    Stomatitis
         subjects affected / exposed
    4 / 30 (13.33%)
    2 / 6 (33.33%)
         occurrences all number
    4
    3
    Oesophagitis
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 6 (0.00%)
         occurrences all number
    3
    0
    Toothache
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    Vomiting
         subjects affected / exposed
    23 / 30 (76.67%)
    3 / 6 (50.00%)
         occurrences all number
    47
    7
    Skin and subcutaneous tissue disorders
    Pain of skin
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    Decubitus ulcer
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    Pruritus
         subjects affected / exposed
    3 / 30 (10.00%)
    0 / 6 (0.00%)
         occurrences all number
    4
    0
    Pruritus generalised
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    Rash maculo-papular
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    Endocrine disorders
    Diabetes insipidus
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    4 / 30 (13.33%)
    1 / 6 (16.67%)
         occurrences all number
    5
    1
    Arthralgia
         subjects affected / exposed
    1 / 30 (3.33%)
    2 / 6 (33.33%)
         occurrences all number
    2
    2
    Musculoskeletal chest pain
         subjects affected / exposed
    2 / 30 (6.67%)
    1 / 6 (16.67%)
         occurrences all number
    2
    1
    Neck pain
         subjects affected / exposed
    3 / 30 (10.00%)
    1 / 6 (16.67%)
         occurrences all number
    3
    3
    Infections and infestations
    Bacteraemia
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    Diverticulitis
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    Ear infection
         subjects affected / exposed
    1 / 30 (3.33%)
    1 / 6 (16.67%)
         occurrences all number
    1
    1
    Nosocomial infection
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    Nasopharyngitis
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    Oral candidiasis
         subjects affected / exposed
    1 / 30 (3.33%)
    1 / 6 (16.67%)
         occurrences all number
    1
    1
    Pneumonia
         subjects affected / exposed
    1 / 30 (3.33%)
    1 / 6 (16.67%)
         occurrences all number
    1
    1
    Sinusitis
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    Respiratory tract infection
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    Skin infection
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    8 / 30 (26.67%)
    2 / 6 (33.33%)
         occurrences all number
    12
    2
    Hyperammonaemia
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    Hyperglycaemia
         subjects affected / exposed
    2 / 30 (6.67%)
    1 / 6 (16.67%)
         occurrences all number
    3
    2
    Hyperkalaemia
         subjects affected / exposed
    3 / 30 (10.00%)
    0 / 6 (0.00%)
         occurrences all number
    4
    0
    Hypoalbuminaemia
         subjects affected / exposed
    1 / 30 (3.33%)
    1 / 6 (16.67%)
         occurrences all number
    4
    1
    Hypocalcaemia
         subjects affected / exposed
    1 / 30 (3.33%)
    1 / 6 (16.67%)
         occurrences all number
    1
    2
    Hypoglycaemia
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    2
    Hypokalaemia
         subjects affected / exposed
    3 / 30 (10.00%)
    1 / 6 (16.67%)
         occurrences all number
    3
    5
    Hypomagnesaemia
         subjects affected / exposed
    5 / 30 (16.67%)
    1 / 6 (16.67%)
         occurrences all number
    6
    1
    Hyponatraemia
         subjects affected / exposed
    3 / 30 (10.00%)
    0 / 6 (0.00%)
         occurrences all number
    7
    0
    Metabolic acidosis
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    14 Oct 2014
    1. Provided more conservative Dose Adjustment Guidelines for nonhematologic toxicities Section 8.2.2 as requested and agreed to, with the FDA; for consistency and ease of investigators, applied similar guidelines to hematologic toxicities. 2. Provided guidance in Section 8.2 Treatment Administration and Schedule, in the event of an emetic event shortly after ingestion of daily dose of CC-486, as agreed with the Agency. 3. Provided consistency between Section 5 ToE and text in Section 6 on bone scan assessments schedules; updated the footnotes in the Table of Events (ToE) with specific hematology, chemistry, and coagulation laboratory parameters being assessed, as agreed with the Agency. 4. An administrative change clarified the definition of PFS in Section 3.1 Primary Endpoints. 5. An administrative change deleted duplicate assessments being conducted on EBV-DNA biomarkers (in plasma and serum) in Sections 3.3 Exploratory Endpoints, Section 6.5 Biomarkers, and those in Section 5 ToE and Section 6 Procedures.
    03 Apr 2015
    1. Established an iDMC as requested by the Competent Authority (CA) in France. The update was reflected in the Protocol Summary, Section 10.1 Statistical Analysis Overview, and Section 10.10.1 iDMC and provided additional monitoring of the safety and efficacy data of this study. 2. Added the secondary endpoint of DCR as requested by the EC in Singapore. 3. In Section 7.3, subjects with undifferentiated or poorly differentiated NPC that was locally advanced or metastatic was clarified to include those subjects who received definitive chemoradiation treatment and had disease progression within 6 months could have been eligible at the investigator’s discretion. 4. Provided further guidance in Section 7.3 regarding Exclusion Criterion #10 on hepatitis, with the addition of new Section 8.2.5 Guidelines for Screening and Management of Hepatitis B and C. 5. Provided further guidance in Section 7.3 Exclusion Criteria, as requested by the CA in Italy with the addition of the new Exclusion Criterion #11 of a subject with active bleeding or a pathological condition that carried a high risk of bleeding, or was at risk of pseudoaneurysm of the internal carotid artery, and carotid blowout syndrome. 6. Created Section 8.2.5 Guidelines for Screening and Management of Hepatitis B and C to provide further guidance in the screening and management of subjects for hepatitis. 7. Updated Section 1.3.2 CC-486 in NPC as of January 2015 data, and updated Section 1.4 Rationale for further clarity. 8. Made minor changes throughout to align Section 5 ToE, Section 6 Procedures, Section 6.1 Treatment Period, and Section 18 References, with the guidance described in Section 8.2.5 Guidelines for Screening and Management of Hepatitis B and C. 9. Promoted greater consistency within Table 4: Dose Adjustments and Dose Delays for Toxicity. 10. Clarified Section 9.1 Permitted Concomitant Medication and Procedures and aligned with new guidance on the screening and management of subjects for hepatitis.
    23 Sep 2016
    1. Added language to allow subjects who were still receiving CC-486 to continue receiving treatment in a CC-486 roll-over protocol.

    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.
    The review of the efficacy data from the trial participants did not support proceeding to Stage 2 as the protocol-defined criteria of > 4 responders (a best response of CR or PR) in Stage 1 was not reached and the study was terminated.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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