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    Clinical Trial Results:
    A Phase 2, Randomized, Open-Label Study Comparing Oral Ixazomib/Dexamethasone and Oral Pomalidomide/Dexamethasone in Relapsed and/or Refractory Multiple Myeloma

    Summary
    EudraCT number
    		 2016-004742-28
    Trial protocol
    		 CZ   SE   GB   DE   DK   NL   BE   ES   GR   IT  
    Global end of trial date
    26 Nov 2021

    Results information
    Results version number
    		 v3(current)
    This version publication date
    15 Dec 2022
    First version publication date
    19 Aug 2021
    Other versions
    		 v1 , v2
    Version creation reason
    • New data added to full data set
    Final results posted after the interim results.

    Trial information

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    Trial identification
    Sponsor protocol code
    C16029
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03170882
    WHO universal trial number (UTN)
    		 U1111-1188-2677
    Sponsors
    Sponsor organisation name
    Takeda
    Sponsor organisation address
    95 Hayden Avenue, Lexington, MA, United States, 02421
    Public contact
    Study Director, Takeda, TrialDisclosures@takeda.com
    Scientific contact
    Study Director, Takeda, TrialDisclosures@takeda.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
    26 Nov 2021
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    26 Nov 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main aim of this study was to learn if ixazomib, given with dexamethasone, stops the cancer from getting worse in people with relapsed or refractory multiple myeloma. It was compared to another medicine called pomalidomide, given with dexamethasone with people with the same condition.
    Protection of trial subjects
    All study participants were required to read and sign an Informed Consent Form.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 Aug 2017
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Germany: 7
    Country: Number of subjects enrolled
    Ireland: 9
    Country: Number of subjects enrolled
    Turkey: 7
    Country: Number of subjects enrolled
    Spain: 6
    Country: Number of subjects enrolled
    Israel: 5
    Country: Number of subjects enrolled
    Czechia: 4
    Country: Number of subjects enrolled
    Netherlands: 4
    Country: Number of subjects enrolled
    Greece: 3
    Country: Number of subjects enrolled
    Sweden: 3
    Country: Number of subjects enrolled
    Australia: 10
    Country: Number of subjects enrolled
    Russian Federation: 23
    Country: Number of subjects enrolled
    Norway: 15
    Country: Number of subjects enrolled
    Italy: 14
    Country: Number of subjects enrolled
    France: 12
    Worldwide total number of subjects
    122
    EEA total number of subjects
    77
    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)
    31
    From 65 to 84 years
    88
    85 years and over
    3

    Subject disposition

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    Recruitment
    Recruitment details
    		 Participants took part in the study at 54 investigative sites in Australia, Turkey, Czech Republic, France, Germany, Italy, Netherlands, Norway, Spain, Israel, United Kingdom, Sweden, Greece, and Russian Federation from 01 August 2017 up to 26 November 2021.

    Pre-assignment
    Screening details
    		 Participants with a diagnosis of relapsed and/or refractory multiple myeloma (RRMM) who received at least 2 prior lines of therapy were enrolled in 2:3 ratio to receive pomalidomide + dexamethasone or ixazomib + dexamethasone in this study.

    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
    		 Pomalidomide 4 mg + Dexamethasone 40 mg
    Arm description
    		 Pomalidomide 4 mg, capsules, orally, once daily on Days 1 to 21 of each 28-day cycle, plus dexamethasone 40 mg, (or 20 mg if participant is aged >=75 years), tablets, orally, once daily on Days 1, 8, 15, and 22 of each 28-day cycle until disease progression, unacceptable toxicity, withdrawal of consent, or sponsor termination of study up to 2 years.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Pomalidomide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Pomalidomide capsules

    Investigational medicinal product name
    Dexamethasone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Dexamethasone tablets

    Arm title
    		 Ixazomib 4 mg + Dexamethasone 20 mg
    Arm description
    		 Ixazomib 4 mg as starting dose, capsules, orally, once daily on Days 1, 8, and 15 of each 28-day cycle, with escalation to 5.5 mg at the start of Cycle 2 for participants who tolerated the 4 mg dose in Cycle 1, plus dexamethasone 20 mg (or 10 mg if participant is aged >=75 years), tablets, orally, once daily on Days 1, 2, 8, 9, 15, 16, 22, and 23 of every 28-day cycle until disease progression, unacceptable toxicity, withdrawal of consent, or sponsor termination of study up to 2 years.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Dexamethasone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Dexamethasone tablets

    Investigational medicinal product name
    Ixazomib
    Investigational medicinal product code
    Other name
    NINLARO MLN9708
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Ixazomib capsules

    Number of subjects in period 1
    		Pomalidomide 4 mg + Dexamethasone 40 mg Ixazomib 4 mg + Dexamethasone 20 mg
    Started
    49
    73
    Treated: Safety Population
    47
    72
    ITT PRO Population
    45
    70
    Completed
    0
    0
    Not completed
    49
    73
         Death
    17
    29
         Lost to Follow-up
    -
    1
         Withdrawal by Subject
    4
    7
         Reason not Specified
    28
    36

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Pomalidomide 4 mg + Dexamethasone 40 mg
    Reporting group description
    		 Pomalidomide 4 mg, capsules, orally, once daily on Days 1 to 21 of each 28-day cycle, plus dexamethasone 40 mg, (or 20 mg if participant is aged >=75 years), tablets, orally, once daily on Days 1, 8, 15, and 22 of each 28-day cycle until disease progression, unacceptable toxicity, withdrawal of consent, or sponsor termination of study up to 2 years.

    Reporting group title
    Ixazomib 4 mg + Dexamethasone 20 mg
    Reporting group description
    		 Ixazomib 4 mg as starting dose, capsules, orally, once daily on Days 1, 8, and 15 of each 28-day cycle, with escalation to 5.5 mg at the start of Cycle 2 for participants who tolerated the 4 mg dose in Cycle 1, plus dexamethasone 20 mg (or 10 mg if participant is aged >=75 years), tablets, orally, once daily on Days 1, 2, 8, 9, 15, 16, 22, and 23 of every 28-day cycle until disease progression, unacceptable toxicity, withdrawal of consent, or sponsor termination of study up to 2 years.

    Reporting group values
    		 Pomalidomide 4 mg + Dexamethasone 40 mg Ixazomib 4 mg + Dexamethasone 20 mg Total
    Number of subjects
    		 49 73 122
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 13 18 31
        From 65-84 years
    		 36 52 88
        85 years and over
    		 0 3 3
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 67.7 ± 8.33 70.6 ± 8.60 -
    Sex: Female, Male
    Units: participants
        Female
    		 23 38 61
        Male
    		 26 35 61
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 2 3 5
        Not Hispanic or Latino
    		 42 65 107
        Unknown or Not Reported
    		 5 5 10
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0
        Asian
    		 0 1 1
        Native Hawaiian or Other Pacific Islander
    		 0 0 0
        Black or African American
    		 0 1 1
        White
    		 46 69 115
        More than one race
    		 0 0 0
        Unknown or Not Reported
    		 3 2 5
    Region of Enrollment
    Units: Subjects
        Russia
    		 8 15 23
        Norway
    		 7 8 15
        Italy
    		 9 5 14
        France
    		 3 9 12
        Ireland
    		 3 6 9
        Germany
    		 1 6 7
        Turkey
    		 4 3 7
        Spain
    		 2 4 6
        Israel
    		 3 2 5
        Czechia
    		 1 3 4
        Netherlands
    		 2 2 4
        Greece
    		 0 3 3
        Sweden
    		 2 1 3
        Australia
    		 4 6 10
    Baseline Height
    Units: cm
        arithmetic mean (standard deviation)
    		 166.59 ± 8.740 165.01 ± 10.475 -
    Baseline Weight
    Units: kg
        arithmetic mean (standard deviation)
    		 75.75 ± 16.160 74.36 ± 17.426 -
    Baseline Body Surface Area
    Units: m^2
        arithmetic mean (standard deviation)
    		 1.864 ± 0.2203 1.837 ± 0.2430 -

    End points

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    End points reporting groups
    Reporting group title
    Pomalidomide 4 mg + Dexamethasone 40 mg
    Reporting group description
    		 Pomalidomide 4 mg, capsules, orally, once daily on Days 1 to 21 of each 28-day cycle, plus dexamethasone 40 mg, (or 20 mg if participant is aged >=75 years), tablets, orally, once daily on Days 1, 8, 15, and 22 of each 28-day cycle until disease progression, unacceptable toxicity, withdrawal of consent, or sponsor termination of study up to 2 years.

    Reporting group title
    Ixazomib 4 mg + Dexamethasone 20 mg
    Reporting group description
    		 Ixazomib 4 mg as starting dose, capsules, orally, once daily on Days 1, 8, and 15 of each 28-day cycle, with escalation to 5.5 mg at the start of Cycle 2 for participants who tolerated the 4 mg dose in Cycle 1, plus dexamethasone 20 mg (or 10 mg if participant is aged >=75 years), tablets, orally, once daily on Days 1, 2, 8, 9, 15, 16, 22, and 23 of every 28-day cycle until disease progression, unacceptable toxicity, withdrawal of consent, or sponsor termination of study up to 2 years.

    Primary: Progression Free Survival (PFS)

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    End point title
    		 Progression Free Survival (PFS)
    End point description
    PFS:Time from randomisation to first occurrence of confirmed progressive disease(PD) assessed by investigator by International Myeloma Working Group(IMWG) response criteria/death, whichever comes first.PD:Increase of >=25% from nadir in:Serum M component(increase>=0.5g/dl);Urine M-component (increase>=200 mg/24hr);In participants without measurable serum and urine M-protein levels difference between involved and uninvolved free light chain(FLC) increase >10mg/dl;In participants without measurable serum and urine M protein levels, without measurable disease by FLC level:bone marrow plasma cell percentage >=10%;Development of new/increase in size of existing bone lesions/soft tissue plasmacytomas;development of hypercalcemia (>11.5mg/dL corrected serum calcium) attributed solely to plasma cell proliferative disease.ITT Population:all participants randomised. Participants without documentation of PD were censored at date of last response assessment that is stable disease(SD) or better.
    End point type
    Primary
    End point timeframe
    From date of randomisation until first occurrence of confirmed disease progression or death due to any cause, whichever occurs first (Up to approximately 3 years)
    End point values
    		 Pomalidomide 4 mg + Dexamethasone 40 mg Ixazomib 4 mg + Dexamethasone 20 mg
    Number of subjects analysed
    49
    73
    Units: months
        median (confidence interval 95%)
    4.8 (3.745 to 8.542)
    7.1 (3.943 to 11.138)
    Statistical analysis title
    		 Statistical Analysis for PFS
    Comparison groups
    Pomalidomide 4 mg + Dexamethasone 40 mg v Ixazomib 4 mg + Dexamethasone 20 mg
    Number of subjects included in analysis
    122
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.477
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.847
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.535
         upper limit
    		 1.341

    Secondary: Overall Survival (OS)

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    End point title
    		 Overall Survival (OS)
    End point description
    OS was defined as the time from randomisation to death from any cause, up to 3 years are reported. ITT Population included all participants who were randomised. Participants without documented death at the time of analysis were censored at the date last known to be alive. 99999 indicates that median and 95% CI was not estimable due to fewer number of participants with events.
    End point type
    Secondary
    End point timeframe
    From date of randomisation to death due to any cause (Up to approximately 3 years)
    End point values
    		 Pomalidomide 4 mg + Dexamethasone 40 mg Ixazomib 4 mg + Dexamethasone 20 mg
    Number of subjects analysed
    49
    73
    Units: months
        median (confidence interval 95%)
    99999 (13.963 to 99999)
    18.8 (10.973 to 99999)
    Statistical analysis title
    		 Statistical Analysis for OS
    Comparison groups
    Pomalidomide 4 mg + Dexamethasone 40 mg v Ixazomib 4 mg + Dexamethasone 20 mg
    Number of subjects included in analysis
    122
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [1]
    P-value
    		 = 0.265
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.427
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.761
         upper limit
    		 2.677
    Notes
    [1] - HR obtained by unadjusted Cox's proportional hazard regression model stratified by age, ISS and prior lines of therapy. HR <1 was deemed to indicate longer survival time in Ixazomib + Dexamethasone arm as compared to Pomalidomide + Dexamethasone arm.

    Secondary: Percentage of Participants with Overall Response

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    End point title
    		 Percentage of Participants with Overall Response
    End point description
    Overall Response Rate(ORR) was defined as the percentage of participants who achieved partial response(PR), very good partial response(VGPR), or complete response(CR) based on laboratory results and IRC assessment using modified IMWG criteria. PR: >=50% reduction of serum M protein+reduction in 24-hour urinary M protein by>=90% or to <200 mg/24-hour; if M protein is not measurable,>=50% decrease in difference between involved and uninvolved FLC levels is required; if not measurable by FLC,>=50% reduction in bone marrow plasma cells, when baseline value>=30% and; if present at baseline,>=50% reduction in size of soft tissue plasmacytomas is required. VGPR: serum and urine M-protein detectable by immunofixation but not on electrophoresis or>=90% reduction in serum M-protein+urine M-protein level<100 mg/24-hour. CR: negative immunofixation on serum+urine; disappearance of soft tissue plasmacytomas;<5% plasma cells in bone marrow. ITT Population: all participants who were randomised.
    End point type
    Secondary
    End point timeframe
    From date of randomisation until first documentation of CR, VGPR or PR (Up to approximately 3 years)
    End point values
    		 Pomalidomide 4 mg + Dexamethasone 40 mg Ixazomib 4 mg + Dexamethasone 20 mg
    Number of subjects analysed
    49
    73
    Units: percentage of participants
        number (confidence interval 95%)
    41 (27 to 56)
    38 (27 to 50)
    Statistical analysis title
    		 Statistical Analysis for ORR
    Comparison groups
    Pomalidomide 4 mg + Dexamethasone 40 mg v Ixazomib 4 mg + Dexamethasone 20 mg
    Number of subjects included in analysis
    122
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [2]
    P-value
    		 = 0.634
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.43
         upper limit
    		 1.9
    Notes
    [2] - OR was based on logistic regression model with treatment group as categorical predictor variable and age, ISS and prior lines of therapy. OR >1 was deemed to indicate better response in Ixazomib+Dexamethasone arm over Pomalidomide+Dexamethasone arm.

    Secondary: Duration of Response (DOR)

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    End point title
    		 Duration of Response (DOR)
    End point description
    DOR:Time from first documentation of CR/PR/VGPR to first documentation of PD.IMWG criteria, PR:>=50%lower of serumMprotein+reduced 24hr urinary Mprotein >=90% to <200 mg/24-hour or >=50%decreaseed difference between involved-uninvolved FLC level/>=50%lower bone marrow (BM) plasmacell,if >=30%at Baseline/>=50%lower size of softtissue plasmacytomas. VGPR: serum+urineprotein detected by immunofixation (IM)/>=90% reduced serum Mprotein+urine Mprotein level <100mg/24hr. CR:negative IM on serum&urine+disappeared soft tissue plasmacytomas+<5%plasmacell in BM. PD:serumMcomponent >=0.5g/dl/urineMcomponent >=200 mg/24hr/ difference between involved-uninvolved FLC level increase >10 mg/dl/BM plasma cell >=10%/developed new/increased size of existing bone lesion/soft tissue plasmacytoma/hypercalcemia. Response Evaluable Population:participants with confirmed PR,or PR/VGPR/CR.Responders were reported.99999=upper limit of 95%CI not estimable due to fewer number of participants with events.
    End point type
    Secondary
    End point timeframe
    From date of first documentation of CR, VGPR or PR until first occurrence of confirmed disease progression or death due to any cause, whichever occurs first (Up to approximately 3 years)
    End point values
    		 Pomalidomide 4 mg + Dexamethasone 40 mg Ixazomib 4 mg + Dexamethasone 20 mg
    Number of subjects analysed
    20
    28
    Units: months
        median (confidence interval 95%)
    14.3 (3.713 to 99999)
    14.8 (10.152 to 19.614)
    No statistical analyses for this end point

    Secondary: Time to Response

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    End point title
    		 Time to Response
    End point description
    Time to response was defined as the time from randomisation to the first documentation of PR/VGPR/CR. Per IMWG criteria, PR: >=50% reduction of serum M protein + reduction in 24-hour urinary M protein by >=90% or to <200 mg/24-hour; if M-protein is not measurable, >=50% decrease in difference between involved and uninvolved FLC levels is required; if not measurable by FLC, >=50% reduction in bone marrow plasma cells, when Baseline value >=30% and; if present at Baseline, >=50% reduction in size of soft tissue plasmacytomas is required. VGPR: serum and urine M-protein detectable by immunofixation but not on electrophoresis or >=90% reduction in serum M-protein + urine M-protein level <100 mg/24-hour. CR: negative immunofixation on serum + urine; disappearance of soft tissue plasmacytomas; <5% plasma cells in bone marrow. Response Evaluable Population included all participants with multiple myeloma who had documentation of a confirmed PR, or PR/VGPR/CR.
    End point type
    Secondary
    End point timeframe
    From date of randomisation until first documentation of CR, VGPR or PR (Up to approximately 3 years)
    End point values
    		 Pomalidomide 4 mg + Dexamethasone 40 mg Ixazomib 4 mg + Dexamethasone 20 mg
    Number of subjects analysed
    49
    73
    Units: months
        median (confidence interval 95%)
    1.1 (0.953 to 2.037)
    2.0 (1.906 to 2.858)
    Statistical analysis title
    		 Statistical Analysis for TOR
    Comparison groups
    Pomalidomide 4 mg + Dexamethasone 40 mg v Ixazomib 4 mg + Dexamethasone 20 mg
    Number of subjects included in analysis
    122
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [3]
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.556
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.288
         upper limit
    		 1.073
    Notes
    [3] - HR was obtained by unadjusted Cox's proportional hazard regression model stratified by age, ISS, prior lines of therapy. HR >1 was deemed to indicate quicker response time in Ixazomib + Dexamethasone arm over Pomalidomide + Dexamethasone arm.

    Secondary: Time to Progression (TTP)

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    End point title
    		 Time to Progression (TTP)
    End point description
    TTP was defined as the time from the date of randomisation to first documentation of PD. Per IMWG criteria, PD required 1 of the following: Increase of >=25% from nadir in: Serum M-component (increase must be >=0.5 g/dl; Urine M-component (increase must be >=200 mg/24-hour); In participants without measurable serum and urine M-protein levels difference between involved and uninvolved FLC levels increase of >10 mg/dl; In participants without measurable serum and urine M protein levels and without measurable disease by FLC level: Bone marrow plasma cell percentage must be >=10%; Development of new or increase in size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (>11.5 mg/dL corrected serum calcium) attributed solely to plasma cell proliferative disease. ITT Population: all participants who were randomised. Participants without documentation of PD at the time of analysis are censored at the date of last response assessment that is SD or better.
    End point type
    Secondary
    End point timeframe
    From date of randomisation until first occurrence of confirmed disease progression or death due to any cause, whichever occurs first (Up to approximately 3 years)
    End point values
    		 Pomalidomide 4 mg + Dexamethasone 40 mg Ixazomib 4 mg + Dexamethasone 20 mg
    Number of subjects analysed
    49
    73
    Units: months
        median (confidence interval 95%)
    5.1 (3.844 to 12.485)
    8.4 (5.684 to 13.306)
    Statistical analysis title
    		 Statistical Analysis for TTP
    Comparison groups
    Pomalidomide 4 mg + Dexamethasone 40 mg v Ixazomib 4 mg + Dexamethasone 20 mg
    Number of subjects included in analysis
    122
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [4]
    P-value
    		 = 0.459
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.83
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.506
         upper limit
    		 1.361
    Notes
    [4] - HR: obtained by unadjusted Cox's proportional hazard regression model stratified by age,ISS,prior lines of therapy. HR<1 was deemed to indicate better disease progression prevention in Ixazomib+Dexamethasone arm over Pomalidomide+Dexamethasone arm.

    Secondary: Health-Related Quality of Life (HRQOL) Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire- Core 30 (EORTC QLQ-C30) Physical Domain Score

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    End point title
    		 Health-Related Quality of Life (HRQOL) Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire- Core 30 (EORTC QLQ-C30) Physical Domain Score
    End point description
    The EORTC QLQ-C30 contains 30 items across 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial difficulties) and a global health status/quality of life (QOL) scale. The physical domain consisted of 5 items covering participant's daily physical activities on a scale from 1 (not at all) to 4 (very much). Raw scores were linearly transformed to a total score between 0-100, with a high score indicating better physical functioning. ITT PRO Population included participants with a measurement at study entry and at least one post study entry measurement for at least 1 subscale on all 3 questionnaires (EORTC QLQ-C30, EORTC Multiple Myeloma Module 20 [QLQ-MY20] and EuroQol 5-Dimensional Health Questionnaire [EQ-5D-5L]). 'n' indicates number analysed are the number of participants with data available for analyses at the given timepoint.
    End point type
    Secondary
    End point timeframe
    Baseline and End of Treatment (EOT) (Up to 28 cycles, each cycle was of 28 days)
    End point values
    		 Pomalidomide 4 mg + Dexamethasone 40 mg Ixazomib 4 mg + Dexamethasone 20 mg
    Number of subjects analysed
    45
    70
    Units: score on a scale
    arithmetic mean (standard deviation)
        Baseline (n= 45, 70)
    67.0 ± 21.97
    67.9 ± 22.08
        End of Treatment (n= 28, 42)
    52.4 ± 28.03
    56.5 ± 26.10
    No statistical analyses for this end point

    Secondary: HRQOL Based on EORTC QLQ-C30 SubScale Score

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    End point title
    		 HRQOL Based on EORTC QLQ-C30 SubScale Score
    End point description
    The EORTC QLQ-C30 contains 30 items across 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial difficulties) and a QOL scale. Most of the 30 items had 4 response levels (not at all, a little, quite a bit, and very much), with 2 questions relying on a 7-point numeric rating scale. Each subscale raw score were linearly transformed to a total score between 0 to 100. For the functional scales and the global health status/QOL scale, higher scores represent better QOL; for the symptom scales, lower scores represent better QOL. The Physical domain of the functional subscale is reported in the secondary outcome measure 7.ITT PRO Population:participants with a measurement at study entry and at least one post study entry measurement for at least 1 subscale on all 3 questionnaires(EORTC QLQ-C30,EORTC QLQ-MY20 & EQ-5D-5L).'n' indicates number
    End point type
    Secondary
    End point timeframe
    Baseline and End of Treatment (Up to 28 cycles, each cycle was of 28 days)
    End point values
    		 Pomalidomide 4 mg + Dexamethasone 40 mg Ixazomib 4 mg + Dexamethasone 20 mg
    Number of subjects analysed
    45
    70
    Units: score on a scale
    arithmetic mean (standard deviation)
        Global Health Status/QoL:Baseline(n=45,70)
    57.0 ± 20.72
    60.8 ± 21.16
        Global Health Status/QoL:EOT(n=27,42)
    47.8 ± 19.56
    48.2 ± 19.61
        Role(FS):Baseline(n=45,70)
    67.4 ± 28.42
    67.9 ± 29.67
        Role(FS):EOT(n=28,42)
    47.6 ± 27.86
    49.2 ± 27.04
        Emotional (FS):Baseline(n=45,70)
    74.9 ± 21.19
    83.1 ± 21.70
        Emotional (FS):EOT(n= 28,42)
    67.6 ± 25.19
    72.8 ± 22.62
        Cognitive (FS):Baseline (n=45,70)
    79.6 ± 20.38
    84.0 ± 20.74
        Cognitive (FS):EOT(n=28,42)
    69.6 ± 27.61
    77.4 ± 22.64
        Social (FS):Baseline (n=45,70)
    72.2 ± 29.94
    75.7 ± 27.02
        Social (FS):EOT(n=28,42)
    63.1 ± 27.35
    69.8 ± 24.76
        Fatigue (SS):Baseline (n=45,70)
    60.0 ± 22.89
    61.0 ± 23.07
        Fatigue (SS):EOT(n=28,42)
    50.8 ± 25.02
    50.3 ± 25.77
        Nausea/Vomiting (SS):Baseline(n=45,70)
    96.7 ± 8.41
    94.8 ± 11.54
        Nausea/Vomiting (SS):EOT(n=28,42)
    88.7 ± 15.75
    92.9 ± 16.52
        Pain (SS):Baseline(n=45,70)
    61.1 ± 30.77
    65.2 ± 24.70
        Pain (SS): EOT(n=28,42)
    51.2 ± 26.42
    53.2 ± 28.33
        Dyspnea(SS):Baseline(n=45,70)
    25.2 ± 28.56
    19.0 ± 25.74
        Dyspnea (SS):EOT(n=28,42)
    40.5 ± 30.57
    24.6 ± 26.61
        Insomnia (SS):Baseline(n=45,70)
    32.6 ± 29.72
    29.5 ± 31.87
        Insomnia (SS):EOT(n=28,42)
    36.9 ± 34.35
    29.4 ± 34.69
        Appetite Loss (SS): Baseline(n=45,70)
    22.2 ± 27.52
    14.3 ± 22.39
        Appetite Loss (SS):EOT(n=28,42)
    34.5 ± 34.52
    23.0 ± 28.02
        Constipation (SS):Baseline(n=45,70)
    13.3 ± 23.99
    11.4 ± 20.37
        Constipation (SS):EOT(n=28,42)
    25.0 ± 34.69
    19.8 ± 29.50
        Diarrhea (SS):Baseline(n=45,70)
    17.8 ± 23.14
    16.7 ± 23.23
        Diarrhea (SS):EOT(n=28,42)
    19.0 ± 26.34
    16.3 ± 25.95
        Financial Difficulties (SS):Baseline(n=45,70)
    22.2 ± 27.52
    17.1 ± 25.85
        Financial Difficulties (SS):EOT(n=28,42)
    16.7 ± 21.28
    12.7 ± 22.03
    No statistical analyses for this end point

    Secondary: HRQOL Based on EORTC Multiple Myeloma Module 20 (EORTC QLQ-MY20) Score

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    End point title
    		 HRQOL Based on EORTC Multiple Myeloma Module 20 (EORTC QLQ-MY20) Score
    End point description
    The EORTC QLQ-MY20 has 20 items across 4 independent subscales, 2 symptoms scales (disease symptoms, side effects of treatment), and 2 functional subscales (body image, future perspective). Scores were averaged and transformed to 0-100 scale. Higher scores for the future perspective scale indicate better perspective of the future, for the body image scale indicate better body image and for the disease symptoms scale indicate higher level of symptomatology. ITT PRO Population included participants with a measurement at study entry and at least one post study entry measurement for at least 1 subscale on all 3 questionnaires (EORTC QLQ-C30, EORTC QLQ-MY20 and EQ-5D-5L). 'n' indicates number analysed are the number of participants with data available for analyses at the given timepoint.
    End point type
    Secondary
    End point timeframe
    Baseline and End of Treatment (Up to 28 cycles, each cycle was of 28 days)
    End point values
    		 Pomalidomide 4 mg + Dexamethasone 40 mg Ixazomib 4 mg + Dexamethasone 20 mg
    Number of subjects analysed
    45
    70
    Units: score on a scale
    arithmetic mean (standard deviation)
        Disease Symptoms: Baseline (n= 45, 70)
    73.2 ± 17.06
    72.4 ± 21.31
        Disease Symptoms: EOT (n= 28, 41)
    73.5 ± 17.75
    68.9 ± 23.09
        Side Effects of Treatment: Baseline (n= 45, 70)
    81.0 ± 13.45
    81.4 ± 13.30
        Side Effects of Treatment: EOT (n= 28, 41)
    74.4 ± 17.84
    77.8 ± 14.47
        Body Image: Baseline (n= 45, 70)
    81.5 ± 23.09
    82.9 ± 23.90
        Body Image: EOT (n= 28, 41)
    75.0 ± 30.93
    83.7 ± 23.71
        Future Perspective:Baseline(n=45,70)
    58.8 ± 23.29
    67.5 ± 24.03
        Future Perspective:EOT (n= 28, 41)
    57.9 ± 28.26
    64.0 ± 19.21
    No statistical analyses for this end point

    Secondary: Number of Participants with Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score

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    End point title
    		 Number of Participants with Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score
    End point description
    EQ-5D-5L comprises of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each rated on 5 levels: 1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, 5= extremely severe problems. Higher scores indicated greater levels of problems across the five dimensions. ITT PRO Population included participants with a measurement at study entry and at least one post study entry measurement for at least 1 subscale on all 3 questionnaires (EORTC QLQ-C30, EORTC QLQ-MY20 and EQ-5D-5L). Overall number of participants analysed are the number of participants with data available for analyses. Self-Care – SC; Usual Activities - UA
    End point type
    Secondary
    End point timeframe
    End of Treatment (Up to 28 cycles, each cycle was of 28 days)
    End point values
    		 Pomalidomide 4 mg + Dexamethasone 40 mg Ixazomib 4 mg + Dexamethasone 20 mg
    Number of subjects analysed
    27
    41
    Units: participants
        Mobility(M):1=I Have no Problems in Walking About
    5
    9
        M:2=I Have Slight Problems in Walking About
    6
    12
        M:3=I Have Moderate Problems in Walking About
    8
    11
        M:4=I Have Severe Problems in Walking About
    8
    8
        M:5=I am Unable to Walk About
    0
    1
        SC:1=I Have no Problems Washing or Dressing Myself
    13
    21
        SC:2= Have Slight Problems Washing/Dressing Myself
    6
    10
        SC:3=I Have Moderate Problems Washing/Dressing
    5
    4
        SC:4=I Have Severe Problems Washing/Dressing
    3
    4
        SC:5=I am Unable to Wash or Dress Myself
    0
    2
        UA:1=I Have no Problems Doing my UA
    4
    10
        UA:2=I Have Slight Problems Doing my UA
    7
    9
        UA:3=I Have Moderate Problems Doing my UA
    8
    12
        UA:4=I Have Severe Problems Doing my UA
    7
    7
        UA:5=I am Unable to do my UA
    1
    3
        Pain/Discomfort:1=I Have no Pain or Discomfort
    3
    8
        Pain/Discomfort:2=I Have Slight Pain or Discomfort
    5
    10
        Pain/Discomfort:3=I Have Moderate Pain/Discomfort
    13
    15
        Pain/Discomfort:4=I Have Severe Pain/Discomfort
    6
    6
        Pain/Discomfort:5=I Have Extreme Pain/Discomfort
    0
    2
        Anxiety/Depression:1=I Have no Pain/Discomfort
    6
    19
        Anxiety/Depression:2=I Have no Pain/Discomfort
    8
    13
        Anxiety/Depression:3=I Have no Pain/Discomfort
    11
    6
        Anxiety/Depression:4=I Have no Pain/Discomfort
    2
    1
        Anxiety/Depression:5=I Have no Pain/Discomfort
    0
    2
    No statistical analyses for this end point

    Secondary: HRQOL Based on EuroQol Visual Analogue Scale (EQ VAS) Score

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    End point title
    		 HRQOL Based on EuroQol Visual Analogue Scale (EQ VAS) Score
    End point description
    The EQ VAS records the respondent's self-rated health on a 20 centimeter (cm), vertical, visual analogue scale ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). The scores from all dimensions were combined into a single index score that was reported, where higher score was better quality of life. ITT PRO Population included participants with a measurement at study entry and at least one post study entry measurement for at least 1 subscale on all 3 questionnaires (EORTC QLQ-C30, EORTC QLQ-MY20 and EQ-5D-5L). 'n' indicates number analysed are the number of participants with data available for analyses at the given timepoint.
    End point type
    Secondary
    End point timeframe
    Baseline and End of Treatment (Up to 28 cycles, each cycle was of 28 days)
    End point values
    		 Pomalidomide 4 mg + Dexamethasone 40 mg Ixazomib 4 mg + Dexamethasone 20 mg
    Number of subjects analysed
    45
    70
    Units: score on a scale
    arithmetic mean (standard deviation)
        Baseline (n= 45, 70)
    59.2 ± 20.96
    64.4 ± 18.21
        End of Treatment (n= 27, 41)
    46.9 ± 19.07
    55.9 ± 19.60
    No statistical analyses for this end point

    Secondary: Health Care Utilization (HU): Number of Participants with at Least one Medical Encounter

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    End point title
    		 Health Care Utilization (HU): Number of Participants with at Least one Medical Encounter
    End point description
    Healthcare resources used during medical encounters included hospitalizations, emergency room stays, or outpatient visits. A hospitalization was defined as at least 1 overnight stay in an Intensive Care Unit and/or non-Intensive Care Unit (acute care unit, palliative care unit, and hospice). ITT Population included all participants who were randomised.
    End point type
    Secondary
    End point timeframe
    Up to approximately 3 years
    End point values
    		 Pomalidomide 4 mg + Dexamethasone 40 mg Ixazomib 4 mg + Dexamethasone 20 mg
    Number of subjects analysed
    49
    73
    Units: participants
        Hospitalizations
    16
    23
        Emergency Room Stays
    9
    11
        Outpatient Visits
    29
    32
    No statistical analyses for this end point

    Secondary: HU: Duration of Medical Encounters

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    End point title
    		 HU: Duration of Medical Encounters
    End point description
    Duration of healthcare resources used during medical encounters including hospitalizations, emergency room stays, or outpatient visits was reported in days. A hospitalization was defined as at least 1 overnight stay in an Intensive Care Unit and/or non-Intensive Care Unit (acute care unit, palliative care unit, and hospice). ITT Population included all participants who were randomised.
    End point type
    Secondary
    End point timeframe
    Up to approximately 3 years
    End point values
    		 Pomalidomide 4 mg + Dexamethasone 40 mg Ixazomib 4 mg + Dexamethasone 20 mg
    Number of subjects analysed
    49
    73
    Units: days
    median (full range (min-max))
        Hospitalizations
    2.0 (1.0 to 6.0)
    1.0 (1.0 to 10.0)
        Emergency Room Stays
    1.0 (1.0 to 3.0)
    1.0 (1.0 to 3.0)
        Outpatient Visits
    4.0 (1.0 to 57.0)
    3.0 (1.0 to 34.0)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From signing of the informed consent up to 30 days after last dose of the study drug (Up to approximately 4 years 3 months)
    Adverse event reporting additional description
    At each visit investigator had to document any occurrence of AEs,abnormal laboratory findings.Any event spontaneously reported by participant or observed by investigator was recorded,irrespective of relation to study treatment.All cause-mortality:all randomized participants(N=49,73).Serious+nonserious:Safety Population participants received>=1dose.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.0
    Reporting groups
    Reporting group title
    Ixazomib 4 mg + Dexamethasone 20 mg
    Reporting group description
    		 Ixazomib 4 mg as starting dose, capsules, orally, once daily on Days 1, 8, and 15 of each 28-day cycle, with escalation to 5.5 mg at the start of Cycle 2 for participants who tolerated the 4 mg dose in Cycle 1, plus dexamethasone 20 mg (or 10 mg if participant is aged >=75 years), tablets, orally, once daily on Days 1, 2, 8, 9, 15, 16, 22, and 23 of every 28-day cycle until disease progression, unacceptable toxicity, withdrawal of consent, or sponsor termination of study up to 2 years.

    Reporting group title
    Pomalidomide 4 mg + Dexamethasone 40 mg
    Reporting group description
    		 Pomalidomide 4 mg, capsules, orally, once daily on Days 1 to 21 of each 28-day cycle, plus dexamethasone 40 mg, (or 20 mg if participant is aged >=75 years), tablets, orally, once daily on Days 1, 8, 15, and 22 of each 28-day cycle until disease progression, unacceptable toxicity, withdrawal of consent, or sponsor termination of study up to 2 years.

    Serious adverse events
    		 Ixazomib 4 mg + Dexamethasone 20 mg Pomalidomide 4 mg + Dexamethasone 40 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    40 / 72 (55.56%)
    26 / 47 (55.32%)
         number of deaths (all causes)
    29
    17
         number of deaths resulting from adverse events
    5
    6
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Plasma cell myeloma
         subjects affected / exposed
    4 / 72 (5.56%)
    3 / 47 (6.38%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 2
    0 / 2
    Bladder transitional cell carcinoma
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cervix carcinoma stage II
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastatic squamous cell carcinoma
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cancer pain
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Venous thrombosis limb
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    1 / 72 (1.39%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Pyrexia
         subjects affected / exposed
    0 / 72 (0.00%)
    2 / 47 (4.26%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Facial pain
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 47 (2.13%)
         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
    Pulmonary embolism
         subjects affected / exposed
    0 / 72 (0.00%)
    2 / 47 (4.26%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Lung consolidation
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Enterobacter test positive
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood sodium decreased
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Scrotal haematoma
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    3 / 72 (4.17%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial tachycardia
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute left ventricular failure
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiomegaly
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure chronic
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 47 (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
    Cerebrovascular accident
         subjects affected / exposed
    1 / 72 (1.39%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral sensorimotor neuropathy
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    3 / 72 (4.17%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    2 / 72 (2.78%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal toxicity
         subjects affected / exposed
    2 / 72 (2.78%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal ulcer
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorder
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Ileus
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticular perforation
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematemesis
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erosive oesophagitis
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Rash maculo-papular
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Exfoliative rash
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Crystal arthropathy
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pathological fracture
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthralgia
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 47 (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
    Pneumonia
         subjects affected / exposed
    9 / 72 (12.50%)
    10 / 47 (21.28%)
         occurrences causally related to treatment / all
    5 / 14
    3 / 14
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Bronchitis
         subjects affected / exposed
    2 / 72 (2.78%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    1 / 72 (1.39%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    H1N1 influenza
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia influenzal
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory syncytial virus infection
         subjects affected / exposed
    2 / 72 (2.78%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory syncytial virus bronchitis
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile infection
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenic infection
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 72 (1.39%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    3 / 72 (4.17%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    2 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract infection viral
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterobacter sepsis
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection fungal
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis E
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rhinovirus infection
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cytomegalovirus viraemia
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sialoadenitis
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 47 (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
    Hypercalcaemia
         subjects affected / exposed
    2 / 72 (2.78%)
    2 / 47 (4.26%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Decreased appetite
         subjects affected / exposed
    1 / 72 (1.39%)
    1 / 47 (2.13%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Malnutrition
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 47 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 47 (2.13%)
         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
    		 Ixazomib 4 mg + Dexamethasone 20 mg Pomalidomide 4 mg + Dexamethasone 40 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    62 / 72 (86.11%)
    45 / 47 (95.74%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    2 / 72 (2.78%)
    3 / 47 (6.38%)
         occurrences all number
    2
    3
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    4 / 72 (5.56%)
    8 / 47 (17.02%)
         occurrences all number
    5
    12
    Fatigue
         subjects affected / exposed
    17 / 72 (23.61%)
    11 / 47 (23.40%)
         occurrences all number
    21
    13
    Oedema peripheral
         subjects affected / exposed
    10 / 72 (13.89%)
    2 / 47 (4.26%)
         occurrences all number
    12
    3
    Pyrexia
         subjects affected / exposed
    4 / 72 (5.56%)
    7 / 47 (14.89%)
         occurrences all number
    4
    12
    Influenza like illness
         subjects affected / exposed
    1 / 72 (1.39%)
    3 / 47 (6.38%)
         occurrences all number
    1
    4
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    5 / 72 (6.94%)
    6 / 47 (12.77%)
         occurrences all number
    5
    6
    Dyspnoea
         subjects affected / exposed
    4 / 72 (5.56%)
    5 / 47 (10.64%)
         occurrences all number
    4
    5
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    16 / 72 (22.22%)
    5 / 47 (10.64%)
         occurrences all number
    16
    6
    Investigations
    Platelet count decreased
         subjects affected / exposed
    9 / 72 (12.50%)
    4 / 47 (8.51%)
         occurrences all number
    17
    7
    Neutrophil count decreased
         subjects affected / exposed
    1 / 72 (1.39%)
    4 / 47 (8.51%)
         occurrences all number
    2
    6
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    5 / 72 (6.94%)
    1 / 47 (2.13%)
         occurrences all number
    5
    1
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    5 / 72 (6.94%)
    4 / 47 (8.51%)
         occurrences all number
    5
    4
    Peripheral sensory neuropathy
         subjects affected / exposed
    19 / 72 (26.39%)
    3 / 47 (6.38%)
         occurrences all number
    27
    3
    Tremor
         subjects affected / exposed
    1 / 72 (1.39%)
    3 / 47 (6.38%)
         occurrences all number
    1
    4
    Headache
         subjects affected / exposed
    4 / 72 (5.56%)
    0 / 47 (0.00%)
         occurrences all number
    5
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    12 / 72 (16.67%)
    18 / 47 (38.30%)
         occurrences all number
    15
    29
    Thrombocytopenia
         subjects affected / exposed
    16 / 72 (22.22%)
    9 / 47 (19.15%)
         occurrences all number
    29
    14
    Neutropenia
         subjects affected / exposed
    1 / 72 (1.39%)
    20 / 47 (42.55%)
         occurrences all number
    2
    34
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    28 / 72 (38.89%)
    13 / 47 (27.66%)
         occurrences all number
    43
    15
    Nausea
         subjects affected / exposed
    12 / 72 (16.67%)
    7 / 47 (14.89%)
         occurrences all number
    13
    9
    Vomiting
         subjects affected / exposed
    10 / 72 (13.89%)
    4 / 47 (8.51%)
         occurrences all number
    10
    6
    Constipation
         subjects affected / exposed
    9 / 72 (12.50%)
    8 / 47 (17.02%)
         occurrences all number
    9
    8
    Abdominal pain upper
         subjects affected / exposed
    2 / 72 (2.78%)
    3 / 47 (6.38%)
         occurrences all number
    2
    3
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    0 / 72 (0.00%)
    5 / 47 (10.64%)
         occurrences all number
    0
    5
    Rash maculo-papular
         subjects affected / exposed
    4 / 72 (5.56%)
    1 / 47 (2.13%)
         occurrences all number
    4
    1
    Dry skin
         subjects affected / exposed
    4 / 72 (5.56%)
    0 / 47 (0.00%)
         occurrences all number
    4
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    8 / 72 (11.11%)
    2 / 47 (4.26%)
         occurrences all number
    8
    2
    Bone pain
         subjects affected / exposed
    6 / 72 (8.33%)
    4 / 47 (8.51%)
         occurrences all number
    6
    4
    Pain in extremity
         subjects affected / exposed
    6 / 72 (8.33%)
    4 / 47 (8.51%)
         occurrences all number
    7
    5
    Muscular weakness
         subjects affected / exposed
    6 / 72 (8.33%)
    4 / 47 (8.51%)
         occurrences all number
    10
    5
    Arthralgia
         subjects affected / exposed
    5 / 72 (6.94%)
    4 / 47 (8.51%)
         occurrences all number
    6
    4
    Muscle spasms
         subjects affected / exposed
    4 / 72 (5.56%)
    4 / 47 (8.51%)
         occurrences all number
    4
    4
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    7 / 72 (9.72%)
    6 / 47 (12.77%)
         occurrences all number
    10
    8
    Upper respiratory tract infection
         subjects affected / exposed
    7 / 72 (9.72%)
    7 / 47 (14.89%)
         occurrences all number
    10
    10
    Urinary tract infection
         subjects affected / exposed
    4 / 72 (5.56%)
    6 / 47 (12.77%)
         occurrences all number
    4
    16
    Nasopharyngitis
         subjects affected / exposed
    3 / 72 (4.17%)
    3 / 47 (6.38%)
         occurrences all number
    4
    4
    Pneumonia
         subjects affected / exposed
    4 / 72 (5.56%)
    4 / 47 (8.51%)
         occurrences all number
    4
    4
    Metabolism and nutrition disorders
    Hypokalaemia
         subjects affected / exposed
    5 / 72 (6.94%)
    2 / 47 (4.26%)
         occurrences all number
    5
    3
    Hyperglycaemia
         subjects affected / exposed
    5 / 72 (6.94%)
    1 / 47 (2.13%)
         occurrences all number
    5
    1
    Decreased appetite
         subjects affected / exposed
    2 / 72 (2.78%)
    4 / 47 (8.51%)
         occurrences all number
    2
    5
    Hypomagnesaemia
         subjects affected / exposed
    1 / 72 (1.39%)
    4 / 47 (8.51%)
         occurrences all number
    1
    4

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    16 Sep 2019
    Amendment 5: Summary of changes: The primary purpose of this amendment was to make following changes: - To conclude the study following the phase 2 portion of the study and not initiate the previously planned phase 3 portion of the study. This change in study design was in response to an assessment of the current landscape of myeloma treatments and a slower rate of efficacy event accumulation than projected in the original study design. - The testing strategy was updated to have a single study analysis, to occur when approximately 80 PFS events were observed, and, correspondingly, to update the PFS assumption and type I error control allocation.
    31 Aug 2020
    Amendment 6: Summary of changes: The primary purpose of this amendment was to make following changes: - Modified the study assessments as the data cutoff date for the study analysis had been reached (31 May 2020). - Only participants who continued to demonstrate clinical benefit but who did not have other means of access to the study drugs continued on the study. Because no further formal statistical analyses were performed, only assessments contributing to long-term safety data were required. Most study assessments besides safety were discontinued to ease the burden of protocol-mandated assessments on participants. Added flexibility in study conduct in unavoidable circumstances (e.g., the COVID-19 pandemic).

    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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