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NIMBUS: A Phase 3, Multicenter, Randomized, Open-Label Study to Compare the Efficacy and Safety of Pomalidomide in Combination With Low-Dose Dexamethasone Versus High-Dose Dexamethasone in Subjects With Refractory Multiple Myeloma or Relapsed and Refractory Multiple Myeloma and Companion Study

Sponsor
Celgene (Industry)
Overall Status
Completed
CT.gov ID
NCT01311687
Collaborator
(none)
455
Enrollment
94
Locations
2
Arms
77.6
Actual Duration (Months)
4.8
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to compare efficacy and safety of pomalidomide in combination with low-dose dexamethasone versus high-dose dexamethasone in subjects with refractory or relapsed and refractory multiple myeloma.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
455 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 3, Muticenter, Randomized, Open-label Study to Compare the Efficacy and Safety of Pomalidomide in Combination With Low-dose Dexamethasone Versus High-dose Dexamethasone in Subjects With Refractory or Relapsed and Refractory Multiple Myeloma
Actual Study Start Date :
Mar 11, 2011
Actual Primary Completion Date :
Mar 1, 2013
Actual Study Completion Date :
Aug 29, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: Pomalidomide + Low-Dose Dexamethasone

Participants received 4 mg pomalidomide administered by mouth on Days 1 to 21 of each 28-day treatment cycle and 40 mg dexamethasone (or 20 mg for participants > 75 years of age) administered by mouth once per day on Days 1, 8, 15, and 22 of each 28-day cycle until disease progression.

Drug: pomalidomide
4 mg pomalidomide capsules administered orally
Other Names:
  • CC-4047
  • Pomalyst®

    • Drug: Dexamethasone
    40 mg dexamethasone (or 20 mg for participants > 75 years of age) tablets administered orally
    Active Comparator: High-Dose Dexamethasone

    Participants received 40 mg dexamethasone (or 20 mg for participants > 75 years of age) administered by mouth once per day on Days 1 to 4, 9 to 12, and 17 to 20 of each 28-day treatment cycle until disease progression.

    Drug: Dexamethasone
    40 mg dexamethasone (or 20 mg for participants > 75 years of age) tablets administered orally

    Outcome Measures

    Primary Outcome Measures

    1. Progression-free Survival (PFS) - Primary Analysis [From randomization until the data cut-off date of 07 September 2012. Maximum duration of follow-up for PFS assessments was 57 weeks.]

      Progression-free survival was calculated as the time from randomization to disease progression as determined by the Independent Response Adjudication Committee based on the International Myeloma Working Group Uniform Response criteria (IMWG), or death on study, whichever occurred earlier. Progressive disease required 1 of the following: • Increase of ≥ 25% from nadir in: o Serum M-component (absolute increase ≥ 0.5 g/dl); o Urine M-component (absolute increase ≥ 200 mg/24 hours); o Bone marrow plasma cell percentage (absolute % ≥ 10%); • Development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas; • Development of hypercalcemia (corrected serum calcium > 11.5 mg/dl) attributed solely to plasma cell proliferative disease.

    2. Progression-free Survival (PFS) With a Later Cut-off Date [From randomization until the data cut-off date of 01 March 2013. Maximum duration of follow-up for PFS assessments was 74 weeks.]

      Progression-free survival was calculated as the time from randomization to disease progression as determined by the Independent Response Adjudication Committee based on the International Myeloma Working Group Uniform Response criteria (IMWG), or death on study, whichever occurred earlier. Progressive disease requires 1 of the following: • Increase of ≥ 25% from nadir in: o Serum M-component (absolute increase ≥ 0.5 g/dl); o Urine M-component (absolute increase ≥ 200 mg/24 hours); o Bone marrow plasma cell percentage (absolute % ≥ 10%); • Development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas; • Development of hypercalcemia (corrected serum calcium > 11.5 mg/dl) attributed solely to plasma cell proliferative disease.

    Secondary Outcome Measures

    1. Number of Participants With Adverse Events (AEs) [From first dose of study drug through to 30 days after the last dose as of the end of the study (29 August 2017); maximum time on treatment was 297, 269, and 239 weeks in the Pomalidomide + LD-Dex, HD-Dex, and cross-over groups respectively.]

      An adverse event is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. A serious AE is any AE occurring at any dose that: • Results in death; • Is life-threatening; • Requires or prolongs existing inpatient hospitalization; • Results in persistent or significant disability/incapacity; • Is a congenital anomaly/birth defect; • Constitutes an important medical event. The Investigator assessed the relationship of each AE to study drug and graded the severity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0): Grade 1 = Mild (no limitation in activity or intervention required); Grade 2 = Moderate (some limitation in activity; no/minimal medical intervention required); Grade 3 = Severe (marked limitation in activity; medical intervention required, hospitalization possible); Grade 4 = Life-threatening; Grade 5 = Death.

    2. Overall Survival - Primary Analysis [From randomization until the data cut-off date of 07 September 2012. Maximum time on follow-up for survival was 70 weeks.]

      Overall survival is calculated as the time from randomization to death from any cause. Overall survival was censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for participants who were lost to follow-up before death was documented.

    3. Overall Survival With a Later Cut-off Date [From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up for survival was 93 weeks.]

      Overall survival is calculated as the time from randomization to death from any cause. Overall survival was censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for participants who were lost to follow-up before death was documented.

    4. Overall Survival Based on the Final Dataset [From randomization until the data cut-off date of 29 August 2017. Maximum time on follow-up for survival was 324 weeks.]

      Overall survival is calculated as the time from randomization to death from any cause. Overall survival was censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for participants who were lost to follow-up before death was documented.

    5. Percentage of Participants With an Objective Response According to International Myeloma Working Group (IMWG) Uniform Response Criteria [From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.]

      Objective response is defined as a best overall response of stringent complete response (SCR), complete response (CR), very good partial response (VGPR) or partial response (PR) based on the Independent Response Adjudication Committee: SCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein and urine M-protein level < 100 mg/24 hours; PR: ≥ 50% reduction of serum M-Protein and reduction in urinary M-protein by ≥ 90% or to < 200 mg/24 hours. In addition to the above, if present at baseline a ≥ 50% reduction in the size of soft tissue plasmacytomas is also required.

    6. Percentage of Participants With Objective Response According to European Group for Blood and Marrow Transplantation (EBMT) Criteria [From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.]

      Objective response defined as a best overall response of complete response (CR) or partial response (PR) based on the Independent Response Adjudication Committee: CR requires all of the following: - Absence of original monoclonal paraprotein in serum and urine by immunofixation maintained at least 42 days. - <5% plasma cell in bone marrow aspirate and on bone marrow biopsy, if performed. - No increase in size or number of lytic bone lesions. - Disappearance of soft tissue plasmacytomas. PR requires all of the following: - ≥ 50% reduction in level of serum monoclonal paraprotein, maintained at least 42 days. - Reduction in 24-hour urinary light chain extraction by ≥ 90% or to < 200 mg, maintained at least 42 days. - For patients with non-secretory myeloma, ≥ 50% reduction in plasma cells in bone marrow aspirate and on biopsy, if performed, for at least 42 days. - ≥ 50% reduction in the size of soft tissue plasmacytomas. - No increase in size or number of lytic bone lesions.

    7. Time to Progression [From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.]

      Time to progression (TTP) is calculated as the time from randomization to the first documented progression confirmed by a blinded, independent Response Adjudication Committee and based on the International Myeloma Working Group Uniform Response criteria (IMWG). Progressive disease requires 1 of the following: • Increase of ≥ 25% from nadir in: o Serum M-component (absolute increase ≥ 0.5 g/dl); o Urine M-component (absolute increase ≥ 200 mg/24 hours); o Bone marrow plasma cell percentage (absolute % ≥ 10%); • Development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas; • Development of hypercalcemia (corrected serum calcium > 11.5 mg/dl) attributed solely to plasma cell proliferative disease.

    8. Time to Response [From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.]

      Time to response is calculated as the time from randomization to the initial documented response (partial response or better) based on IMWG criteria. SCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein and urine M-protein level < 100 mg/24 hours; PR: ≥ 50% reduction of serum M-Protein and reduction in urinary M-protein by ≥ 90% or to < 200 mg/24 hours. If present at baseline a ≥ 50% reduction in size of soft tissue plasmacytomas is also required.

    9. Duration of Response [From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.]

      Duration of response (calculated for responders only) is defined as time from the initial documented response (partial response or better) to confirmed disease progression, based on IMWG criteria assessed by the Independent Response Adjudication Committee.

    10. Time to the First Hemoglobin Improvement [From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.]

      Time to increased hemoglobin, defined as the time from randomization to at least one category improvement from Baseline in common terminology criteria for adverse events (CTCAE) grade for hemoglobin level. Hemoglobin categories are: 1) Normal; 2) CTCAE Grade 1: < lower limit of normal (LLN) to 10.0 g/dL; 3) CTCAE Grade 2: < 10.0 to <8.0 g/dL. Participants with CTCAE Grade 3 anemia or worse at Baseline were excluded from the study.

    11. Time to Improvement in Bone Pain [From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.]

      Time to improvement in bone pain is defined as the time from randomization to at least one category improvement from Baseline in bone pain category. Bone pain was categorized (from best to worst) according to answers to the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for patients with Multiple Myeloma Module (QLQ-MY20), Question 1, "Have you had bone aches or pain?": 1) Not at all, 2) A little, 3) Quite a bit, or 4) Very much.

    12. Time to Improvement in Renal Function [From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.]

      Time to improvement in renal function is defined as the time from randomization to at least one category improvement from Baseline in renal function. Renal Function was categorized as (from best to worst): - Normal: creatinine clearance ≥80 mL/min; - Grade 1: creatinine clearance ≥60 to <80 mL/min; - Grade 2 : creatinine clearance ≥45 to < 60 mL/min. Participants with creatinine clearance < 45 mL/min at baseline were excluded from the study.

    13. Time to Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status [From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.]

      Time to improvement in ECOG performance status defined as the time from randomization until at least a one category improvement from Baseline in ECOG performance status score. The categories of the ECOG Performance Status Scale are as follows: -0: Fully active, able to carry on all pre-disease performance without restriction; -1: Restricted in physically strenuous activity but ambulatory and able to carry our work of a light or sedentary nature, e.g., light housework, office work; -2: Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours. Patients with a score of 3, 4 or 5 were excluded from participating in the study.

    14. Change From Baseline in the European Organization for Research and Treatment of Cancer Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Domain [Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6]

      The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Global Health Status/QOL scale is scored between 0 and 100, with a high score indicating better Global Health Status/QOL. Negative change from Baseline values indicate deterioration in QOL or functioning and positive values indicate improvement.

    15. Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain [Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6]

      The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Physical Functioning Scale is scored between 0 and 100, with a high score indicating better functioning/support. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.

    16. Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain [Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6]

      The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Emotional Functioning Scale is scored between 0 and 100, with a high score indicating better functioning/support. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.

    17. Change From Baseline in the EORTC QLQ-C30 Fatigue Domain [Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6]

      The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Fatigue Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate reduction in fatigue (i.e. improvement in symptom) and positive values indicate increases in fatigue (i.e. worsening of symptom).

    18. Change From Baseline in the EORTC QLQ-C30 Pain Domain [Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6]

      The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Pain Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate reductions in pain (i.e. improvement in symptom) and positive values indicate increases in pain (i.e. worsening of symptom).

    19. Change From Baseline in the European Organization for Research and Treatment of Cancer QoL Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms [Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6]

      The European Organization for Research and Treatment of Cancer QoL Questionnaire for Patients with Multiple Myeloma (EORTC QLQ-MY20) is a 20-question tool used in clinical research to assess health-related quality of life in multiple myeloma patients. The QLQ-MY20 includes four domains (Disease Symptoms, Side-Effects of Treatment, Body Image and Future Perspective). The EORTC QLQ-MY20 Disease Symptoms Scale is scored between 0 and 100, with a high score reflecting a higher level of symptoms. Negative change from Baseline values indicate reduction (i.e. improvement) in symptoms and positive values indicate increase (i.e. worsening) of symptoms.

    20. Change From Baseline in the EORTC QLQ-MY20 Side Effects Domain [Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6]

      The European Organization for Research and Treatment of Cancer QoL Questionnaire for Patients with Multiple Myeloma (EORTC QLQ-MY20) is a 20-question tool used in clinical research to assess health-related quality of life in multiple myeloma patients. The QLQ-MY20 includes four domains (Disease Symptoms, Side-Effects of Treatment, Body Image and Future Perspective). The EORTC QLQ-MY20 Side Effects Scale is scored between 0 and 100, with a high score reflecting a higher level of symptoms. Negative change from Baseline values indicate reduction in side effects (i.e.improvement in symptom) and positive values indicate increase in side effects (i.e. worsening of symptom).

    21. Change From Baseline in the European Quality of Life-5 Dimensions (EQ-5D) Utility Index Score [Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6]

      EQ-5D is a self-administered questionnaire that assesses health-related quality of life (QOL). The EQ-5D descriptive health profile comprises five dimensions of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Each dimension has 3 levels of response: No problem (1), some problems (2), and extreme problems (3). A unique EQ-5D health state is defined by combining one level from each of the five dimensions into a single utility index score. EQ-5D index values range from -0.59 to 1.00 where an EQ-5D score of 1.00 equals "perfect health", a score of 0 equals "death" and a score of -0.59 equals worst imaginable health state. A positive change from Baseline score indicates improvement in health status. A negative change from Baseline score indicates worsening in health status. Negative scores represent the possible though unlikely situation that a patient's QOL is worse than death, i.e. they would rather be dead than living with that QOL

    22. Time to First Worsening of Quality of Life (QOL) Domains [Assessed on Day 1 of the first 6 treatment cycles.]

      Time to worsening in quality of life domains was calculated as the time from Baseline to the first worsened minimally important difference (MID), defined as the smallest change in a QOL score considered important to patients that would lead the patient or clinician to consider a change in therapy. MID thresholds were calculated in Standard Error of Measurement (SEM) units using the Baseline QOL data. Based on the MID, participants were classified as worsened according to the following: For the EORTC QLQ-C30 global health status and functional scales and the EQ-5D health utility score, participants were classified as worsened if their change from Baseline score was less than -1 SEM. For the EORTC QLQ-C30 symptom scores (fatigue and pain) and EORTC QLQ-MY20 disease symptoms and side effects scales, participants were classified as worsened if their change from Baseline score was greater than 1 SEM. See previous outcome measures for definitions of each scale.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Must be ≥ 18 years of age

    • Subjects must have documented diagnosis of multiple myeloma and have measurable disease

    • Subjects must have undergone prior treatment with ≥ 2 treatment lines of anti-myeloma therapy

    • Subjects must have either refractory or relapsed and refractory disease defined as documented disease progression during or within 60 days of completing their last myeloma therapy

    • All subjects must have received at least 2 consecutive cycles of prior treatment that included lenalidomide and bortezomib

    • All subjects must have failed treatment with both lenalidomide and bortezomib in one of the following ways: 1) Documented progressive disease on or within 60 days of completing treatment with lenalidomide and/or bortezomib, or 2) In case of prior response [≥ partial response (PR)] to lenalidomide or bortezomib, subjects must have relapsed within 6 months after stopping treatment with lenalidomide and/or bortezomib-containing regimens, or 3) Subjects who have not had a ≥ minimal response (MR) and have developed intolerance/toxicity after a minimum of two cycles of lenalidomide- and/or bortezomib-containing regimen

    • Patients must have received adequate prior alkylator therapy

    • Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2

    • Females of childbearing potential (FCBP) must not become pregnant for 28 days prior to initiation of study drug, during the study, and for 28 days after discontinuation

    • Females must agree to abstain from breastfeeding during study participation and 28 days after study drug discontinuation

    • Males must agree to use a latex condom during any sexual during the study and for 28 days following discontinuation from this study

    • Males must also agree to refrain from donating semen or sperm while on pomalidomide and for 28 days after discontinuation from this study

    Exclusion Criteria:

    • Any of the following laboratory abnormalities:

    • Absolute neutrophil count (ANC) < 1,000/μL

    • Platelet count < 75,000/ μL for subjects in whom < 50% of bone marrow nucleated cells are plasma cells

    • Creatinine clearance < 45 mL/min

    • Corrected serum calcium > 14 mg/dL

    • Hemoglobin ≤ 8 g/dL

    • Serum glutamic oxaloacetic transaminase (SGOT)/ aspartate aminotransferase (AST) or transaminase, serum glutamic pyruvic (SGPT)/ alanine aminotransferase (ALT) > 3.0 x upper limit of normal (ULN)

    • Serum total bilirubin > 2.0 mg/dL

    • Previous therapy with pomalidomide

    • Hypersensitivity to thalidomide, lenalidomide, or dexamethasone

    • Resistance to high-dose dexamethasone used in the last line of therapy

    • Peripheral neuropathy ≥ Grade 2

    • Subjects who received an allogeneic bone marrow or allogeneic peripheral blood stem cell transplant

    • Subjects who are planning for or who are eligible for stem cell transplant

    • Subjects with any one of the following: 1) Congestive heart failure, 2) Myocardial infarction within 12 months prior to starting study treatment, 3) Unstable or poorly controlled angina pectoris, including Prinzmetal variant angina pectoris

    • Subjects who received any of the following within the last 14 days of initiation of study treatment: 1) Plasmapheresis, 2) Major surgery, 3) Radiation therapy, 4) Use of any anti-myeloma drug therapy

    • Use of any investigational agents within 28 days or 5 half-lives (whichever is longer) of treatment

    • Subjects with conditions requiring chronic steroid or immunosuppressive treatment

    • Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study

    • Incidence of gastrointestinal disease that may significantly alter the absorption of pomalidomide

    • Subjects unable or unwilling to undergo antithrombotic prophylactic treatment

    • Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subjects from signing the informed consent form

    • Pregnant or breastfeeding females

    • Known human immunodeficiency virus (HIV) positivity or active infectious hepatitis A, B, or C

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Mayo Clinic Rochester Minnesota United States 55905
    2 Royal Adelaide Hospital Adelaide South Australia Australia 5000
    3 Peter MacCallum Cancer Institute East Melbourne Victoria Australia 3002
    4 Frankston Hospital Frankston Victoria Australia 3199
    5 Princess Alexandra Hospital Brisbane Australia QLD4102
    6 Royal Prince Alfred Hospital Camperdown Australia 2050
    7 Alfred hospital Melbourne Australia 3004
    8 Sir Charles Gairdner Hospital Nedlands Australia 6009
    9 Calvary Mater Hospital Waratah Australia NSW 2298
    10 Border Medical Oncology Wodonga Australia 3690
    11 Wollongong Hospital Wollongong Australia 2500
    12 UZ Gent Gent Belgium 9000
    13 UZ Leuven Leuven Belgium 3000
    14 CHU UCL Mont-Godinne-Dinant asbl Yvoir Belgium B-5530
    15 Tom Baker Cancer Center Calgary Alberta Canada T2N 4N2
    16 Cross Cancer Institute Edmonton Alberta Canada T6G 1Z2
    17 British Columbia Cancer Agency Vancouver British Columbia Canada V5Z 4E6
    18 James Cancer Hospital Halifax Nova Scotia Canada B3H 2Y9
    19 Juravinski Cancer Centre Hamilton Ontario Canada L8V 5C2
    20 London Health Sciences Centre London Ontario Canada N6C 6B5
    21 University Health Network Toronto Ontario Canada M5G 2M9
    22 Maisonneuve Rosemont Montreal Quebec Canada H1T 2M4
    23 Royal Victoria Hospital McGill Department of Oncology(RVH) Montreal Quebec Canada H3A 1A1
    24 Sir Mortimer B. Davis - Jewish Genl Montreal Quebec Canada H3T 1E2
    25 Charles University General Hospital Praha 2 Czechia 128 08
    26 Hæmatologisk afd. B Aalborg Sygehus Syd Aalborg Denmark 9000
    27 Aarhus University Hospital Arhus C Denmark DK-8000
    28 Odense Universitetshospital Odense C Denmark 5000
    29 Vejle Hospital Vejle Denmark 7100
    30 CHU d'Angers Angers Cedex 01 France 49033
    31 Centre Hospitalier de la cote basque Bayonne France 64109
    32 Centre Hospitalier Departemental La Roche sur Yon France 85025
    33 CHRU de Lille FR Lille France 59037
    34 Institut Paoli-Calmettes Marseille Cedex 9 France 13009
    35 CHRU Nantes Nantes Cedex 1 France 44093
    36 Hopital Saint-Louis Paris, Cedex 10 France 75475
    37 CHU Hôpital St-Antoine Paris France 75571
    38 CHRU - Hopital du Haut Leveque Pessac France 33604
    39 Centre Hospitalier Lyon Sud Pierre Bénite France 69310
    40 Hopital Bretonneau Tours France 37044
    41 Hopital Purpan Tulouse Cedex 9 France 31059
    42 CHU Nancy Vandoeuvre France 54511
    43 Universitatsklinikum Carl Gustav Carus Dresden Germany 01307
    44 Universitatsklinikum Essen Essen Germany 45122
    45 Askepios Klinik St. Georg Hamburg Germany 20099
    46 Universitatsklinikum Heidelberg Heidelberg Germany 69120
    47 Universitatsklinikum Jena Jena Germany 07740
    48 Universitatsklinikum Leipzig Leipzig Germany 04103
    49 University of Tubingen Tübingen Germany 72076
    50 Universitatsklinikum Ulm Ulm Germany 89081
    51 Universitatsklinikum Wurzburg Wuerzburg Germany 97080
    52 Alexandra General Hospital of Athens Athens Greece 11528
    53 Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi Bologna Italy 40138
    54 Clinica Ematologica- A.O.U. San Martino Genova Italy 16132
    55 Oncoematologia, Istituto Nazionale Tumori Fondazione G. Pascale Napoli Italy 80131
    56 AOU San Luigi Gonzaga Orbassano Italy 10043
    57 Universita degli Studi di Padova Padova Italy 35128
    58 Hospital Clinic Placenza Italy 29100
    59 Servizio di Ematologia, A.O. - Arcispedale S.Maria Nuova Reggio Emilia Italy 42100
    60 Univerita La Sapienza Dipartimento di Biotecnologie Cellulari ed Ematologia Rome Italy 00161
    61 Azienda Ospedaliera San Giovanni Battista Torino Italy 10126
    62 VU University Medical Center Amsterdam Netherlands 1081 HV
    63 Erasmus Medical Center Rotterdam Netherlands 3015 CE
    64 University Medical Center Utrecht Utrecht Netherlands 3584 CX
    65 State Institution Hematological Research, Centre of Russian Academy of Medical Science Moscow Russian Federation 125167
    66 State Institution Moscow Regional Research Clinical Institute Moscow Russian Federation 125284
    67 State Educational Institution, Saint Petersburg State Medical University Saint Petersburg Russian Federation 197022
    68 St. Petersburg Research Institute of Hematology and Blood Transfusion St. Petersburg Russian Federation 191024
    69 Hospital Universitari Germans Trias i Pujol Badalona (Barcelona) Spain 08916
    70 Hospital Clinic Provincial de Barcelona Barcelona Spain 08036
    71 Hospital de La Princesa Madrid Spain 28006
    72 Hospital 12 de Octubre Madrid Spain 28041
    73 Hospital Universitario de Salamanca Salamanca Spain 37007
    74 Hospital Donostia San Sebastián (Guipuzcoa) Spain 20014
    75 Hospital Universitario Marques de Valdecilla Santander Spain 39008
    76 Hospital de la Fe Valencia Spain 46009
    77 Department of Hematology Hematology Centre Göteborg Sweden S-413 45
    78 University Hospital in Lund Lund Sweden 221 85
    79 Karolinska University Hospital Huddinge Stockholm Sweden SE 17176
    80 Karolinska University Hospital Stockholm Sweden SE-171 76
    81 Overlakare Medocomcentrum, hematologi Uppsala Sweden 75185
    82 Medizinische Universitatsklinik Berne Switzerland CH - 3010
    83 Hopitaux Universitaires de Geneve-HUG Geneva Switzerland 1205
    84 UniversitatSspital Zurich Zürich Switzerland 8091
    85 Royal Bournemouth Hospital Bournemouth United Kingdom BH7 7DW
    86 St James's University Hospital Leeds United Kingdom LS9 7TF
    87 St.Bartholomew's Hospital London United Kingdom EC1A 7BE
    88 King's College Hospital London United Kingdom SE5 9RS
    89 Freeman Hospital Newcastle Upon Tyne United Kingdom NE7 7DN
    90 Nottingham City Hospital Nottingham United Kingdom NG5 1PB
    91 Derriford Hospital Plymouth United Kingdom PL6 8DH
    92 Royal Hallamshire HospitalSheffield Teaching Hospitals NHS Trust Sheffield United Kingdom S10 2JF
    93 The Royal Marsden Hospital Sutton-Surrey United Kingdom SM2 5PT
    94 The Royal Wolverhampton Hospital NHS Trust Wolverhampton United Kingdom WV10 0QP

    Sponsors and Collaborators

    • Celgene

    Investigators

    • Study Director: Lars Sternas, MD, PhD, Celgene

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Celgene
    ClinicalTrials.gov Identifier:
    NCT01311687
    Other Study ID Numbers:
    • CC-4047-MM-003
    • 2010-019820-30
    First Posted:
    Mar 9, 2011
    Last Update Posted:
    Oct 24, 2018
    Last Verified:
    Sep 1, 2018
    Keywords provided by Celgene
    Myeloma
    Multiple Myeloma
    Relapsed Multiple Myeloma
    Relapsed and Refractory Multiple Myeloma
    Refractory Myeloma
    Resistant Multiple Myeloma
    Treatment-resistant Multiple Myeloma
    Pomalidomide
    Lenalidomide-resistant
    Bortezomib-resistant
    Additional relevant MeSH terms:
    Multiple Myeloma
    Neoplasms, Plasma Cell
    Dexamethasone
    Pomalidomide

    Study Results

    Participant Flow

    Recruitment Details The study was conducted at 93 sites: 68 sites in Europe, 10 sites in Australia, 10 sites in Canada, 4 sites in Russia, and 1 site in the United States (US) from 18 March 2011 to 29 August 2017.
    Pre-assignment Detail Participants were randomized in a 2:1 ratio. Treatment phase discontinuation occurred when a participant had confirmed progressive disease. Participants who did not progress but who were intolerant to treatment, or no longer wished to receive study treatment entered the progression-free survival (PFS) follow-up period until disease progression.
    Arm/Group Title Pomalidomide Plus Low-Dose Dexamethasone High-Dose Dexamethasone (HD-Dex)
    Arm/Group Description Participants received 4 mg pomalidomide administered by mouth on Days 1-21 of each 28-day treatment cycle and 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression. Participants received 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1 through 4, 9 through 12, and 17 through 20 of a 28-day cycle until disease progression.
    Period Title: Treatment Phase
    STARTED 302 153
    Received Study Drug 300 150
    Crossed-over to Pomalidomide 0 11
    COMPLETED 302 153
    NOT COMPLETED 0 0
    Period Title: Treatment Phase
    STARTED 11 8
    Crossed-over to Pomalidomide 11 0
    COMPLETED 11 8
    NOT COMPLETED 0 0

    Baseline Characteristics

    Arm/Group Title Pomalidomide Plus Low-Dose Dexamethasone High-Dose Dexamethasone Total
    Arm/Group Description Participants received 4 mg pomalidomide administered by mouth on Days 1-21 of each 28-day treatment cycle and 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression. Participants received 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1 through 4, 9 through 12, and 17 through 20 of a 28-day cycle until disease progression. Total of all reporting groups
    Overall Participants 302 153 455
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    63.6
    (9.33)
    63.7
    (9.56)
    63.6
    (9.40)
    Age, Customized (Count of Participants)
    ≤ 75 Years Old
    278
    92.1%
    141
    92.2%
    419
    92.1%
    > 75 Years Old
    24
    7.9%
    12
    7.8%
    36
    7.9%
    Sex: Female, Male (Count of Participants)
    Female
    121
    40.1%
    66
    43.1%
    187
    41.1%
    Male
    181
    59.9%
    87
    56.9%
    268
    58.9%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    27
    8.9%
    14
    9.2%
    41
    9%
    Not Hispanic or Latino
    228
    75.5%
    104
    68%
    332
    73%
    Unknown or Not Reported
    47
    15.6%
    35
    22.9%
    82
    18%
    Race/Ethnicity, Customized (Count of Participants)
    Asian
    4
    1.3%
    0
    0%
    4
    0.9%
    Black or African American
    4
    1.3%
    3
    2%
    7
    1.5%
    White
    244
    80.8%
    113
    73.9%
    357
    78.5%
    Other
    2
    0.7%
    2
    1.3%
    4
    0.9%
    Not collected
    48
    15.9%
    35
    22.9%
    83
    18.2%
    Participants with Prior Anti-Myeloma (MM) Therapies (Count of Participants)
    Count of Participants [Participants]
    302
    100%
    153
    100%
    455
    100%
    Time from First Pathologic Diagnosis (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    6.2
    (4.02)
    6.5
    (3.63)
    6.3
    (3.89)
    Stratification Factor 2: Disease Population (Count of Participants)
    Disease Population Group 1
    249
    82.5%
    125
    81.7%
    374
    82.2%
    Disease Population Group 2
    8
    2.6%
    5
    3.3%
    13
    2.9%
    Disease Population Group 3
    45
    14.9%
    23
    15%
    68
    14.9%
    Stratification Factor 3: Number of Prior Anti-MM Therapies (Count of Participants)
    2 Prior Anti-MM Therapies
    17
    5.6%
    8
    5.2%
    25
    5.5%
    > 2 Prior Anti-MM Therapies
    285
    94.4%
    145
    94.8%
    430
    94.5%
    Multiple Myeloma Stage before Study Entry (Count of Participants)
    Stage I
    81
    26.8%
    36
    23.5%
    117
    25.7%
    Stage II
    115
    38.1%
    56
    36.6%
    171
    37.6%
    Stage III
    92
    30.5%
    53
    34.6%
    145
    31.9%
    Missing
    14
    4.6%
    8
    5.2%
    22
    4.8%

    Outcome Measures

    1. Primary Outcome
    Title Progression-free Survival (PFS) - Primary Analysis
    Description Progression-free survival was calculated as the time from randomization to disease progression as determined by the Independent Response Adjudication Committee based on the International Myeloma Working Group Uniform Response criteria (IMWG), or death on study, whichever occurred earlier. Progressive disease required 1 of the following: • Increase of ≥ 25% from nadir in: o Serum M-component (absolute increase ≥ 0.5 g/dl); o Urine M-component (absolute increase ≥ 200 mg/24 hours); o Bone marrow plasma cell percentage (absolute % ≥ 10%); • Development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas; • Development of hypercalcemia (corrected serum calcium > 11.5 mg/dl) attributed solely to plasma cell proliferative disease.
    Time Frame From randomization until the data cut-off date of 07 September 2012. Maximum duration of follow-up for PFS assessments was 57 weeks.

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat population
    Arm/Group Title Pomalidomide Plus Low-Dose Dexamethasone High-Dose Dexamethasone
    Arm/Group Description Participants received 4 mg pomalidomide administered by mouth on Days 1-21 of each 28-day treatment cycle and 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression. Participants received 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1 through 4, 9 through 12, and 17 through 20 of a 28-day cycle until disease progression.
    Measure Participants 302 153
    Median (95% Confidence Interval) [weeks]
    15.7
    8.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pomalidomide Plus Low-Dose Dexamethasone, High-Dose Dexamethasone
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Stratified Log Rank Test
    Comments Stratified by age, disease population, and prior number of anti myeloma therapy.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.45
    Confidence Interval (2-Sided) 95%
    0.35 to 0.59
    Parameter Dispersion Type:
    Value:
    Estimation Comments Hazard ratio is for Pomalidomide Plus Low-Dose Dexamethasone : High Dose Dexamethasone
    2. Primary Outcome
    Title Progression-free Survival (PFS) With a Later Cut-off Date
    Description Progression-free survival was calculated as the time from randomization to disease progression as determined by the Independent Response Adjudication Committee based on the International Myeloma Working Group Uniform Response criteria (IMWG), or death on study, whichever occurred earlier. Progressive disease requires 1 of the following: • Increase of ≥ 25% from nadir in: o Serum M-component (absolute increase ≥ 0.5 g/dl); o Urine M-component (absolute increase ≥ 200 mg/24 hours); o Bone marrow plasma cell percentage (absolute % ≥ 10%); • Development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas; • Development of hypercalcemia (corrected serum calcium > 11.5 mg/dl) attributed solely to plasma cell proliferative disease.
    Time Frame From randomization until the data cut-off date of 01 March 2013. Maximum duration of follow-up for PFS assessments was 74 weeks.

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat population
    Arm/Group Title Pomalidomide Plus Low-Dose Dexamethasone High-Dose Dexamethasone
    Arm/Group Description Participants received 4 mg pomalidomide administered by mouth on Days 1-21 of each 28-day treatment cycle and 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression. Participants received 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1 through 4, 9 through 12, and 17 through 20 of a 28-day cycle until disease progression.
    Measure Participants 302 153
    Median (95% Confidence Interval) [weeks]
    16.0
    8.1
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pomalidomide Plus Low-Dose Dexamethasone, High-Dose Dexamethasone
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Stratified log-rank test
    Comments Stratified by age, disease population, and prior number of anti myeloma therapy.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.49
    Confidence Interval (2-Sided) 95%
    0.39 to 0.61
    Parameter Dispersion Type:
    Value:
    Estimation Comments Hazard ratio is for Pomalidomide Plus Low-Dose Dexamethasone : High Dose Dexamethasone
    3. Secondary Outcome
    Title Number of Participants With Adverse Events (AEs)
    Description An adverse event is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. A serious AE is any AE occurring at any dose that: • Results in death; • Is life-threatening; • Requires or prolongs existing inpatient hospitalization; • Results in persistent or significant disability/incapacity; • Is a congenital anomaly/birth defect; • Constitutes an important medical event. The Investigator assessed the relationship of each AE to study drug and graded the severity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0): Grade 1 = Mild (no limitation in activity or intervention required); Grade 2 = Moderate (some limitation in activity; no/minimal medical intervention required); Grade 3 = Severe (marked limitation in activity; medical intervention required, hospitalization possible); Grade 4 = Life-threatening; Grade 5 = Death.
    Time Frame From first dose of study drug through to 30 days after the last dose as of the end of the study (29 August 2017); maximum time on treatment was 297, 269, and 239 weeks in the Pomalidomide + LD-Dex, HD-Dex, and cross-over groups respectively.

    Outcome Measure Data

    Analysis Population Description
    Safety population (all randomized participants who received at least one dose of study drug (either pomalidomide or dexamethasone)).
    Arm/Group Title Pomalidomide Plus Low-Dose Dexamethasone High-Dose Dexamethasone HD-Dex / Pomalidomide
    Arm/Group Description Participants received 4 mg pomalidomide administered by mouth on Days 1-21 of each 28-day treatment cycle and 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression. Participants received 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1 through 4, 9 through 12, and 17 through 20 of a 28-day cycle until disease progression, or until cross-over to pomalidomide. Data are up to the time of cross-over. Participants initially randomized to high-dose dexamethasone (HD-Dex) crossed over to receive 4 mg pomalidomide administered by mouth on Days 1-21 of each 28-day treatment cycle, with or without low-dose dexamethasone (40 mg for participants ≤ 75 years or 20 mg for participants > 75 years of age, administered orally once per day on Days 1, 8, 15, and 22 of each 28-day cycle) at the discretion of the investigator. Data include AEs that occurred after cross-over to pomalidomide.
    Measure Participants 300 150 11
    Any adverse event
    298
    98.7%
    149
    97.4%
    11
    2.4%
    Grade 3-4 adverse events
    266
    88.1%
    127
    83%
    8
    1.8%
    AE related to pomalidomide
    251
    83.1%
    0
    0%
    11
    2.4%
    AE related to dexamethasone
    205
    67.9%
    115
    75.2%
    5
    1.1%
    AE related to either study drug
    271
    89.7%
    115
    75.2%
    11
    2.4%
    Grade 3-4 AE related to pomalidomide
    199
    65.9%
    0
    0%
    6
    1.3%
    Grade 3-4 AE related to dexamethasone
    114
    37.7%
    70
    45.8%
    2
    0.4%
    Grade 3-4 AE related to either study drug
    212
    70.2%
    70
    45.8%
    6
    1.3%
    Grade 5 adverse events
    46
    15.2%
    21
    13.7%
    1
    0.2%
    Serious adverse events (SAEs)
    195
    64.6%
    80
    52.3%
    4
    0.9%
    SAE related to pomalidomide
    89
    29.5%
    0
    0%
    1
    0.2%
    SAE related to dexamethasone
    73
    24.2%
    36
    23.5%
    0
    0%
    SAE related to either study drug
    98
    32.5%
    36
    23.5%
    1
    0.2%
    SAE leading to discontinuation of pomalidomide
    20
    6.6%
    0
    0%
    1
    0.2%
    SAE leading to discontinuation of dexamethasone
    20
    6.6%
    14
    9.2%
    1
    0.2%
    SAE leading to discontinuation of either study dru
    23
    7.6%
    14
    9.2%
    1
    0.2%
    AE leading to discontinuation of pomalidomide
    30
    9.9%
    0
    0%
    1
    0.2%
    AE leading to discontinuation of dexamethasone
    34
    11.3%
    16
    10.5%
    1
    0.2%
    AE leading to discontinuation of either study drug
    38
    12.6%
    16
    10.5%
    1
    0.2%
    4. Secondary Outcome
    Title Overall Survival - Primary Analysis
    Description Overall survival is calculated as the time from randomization to death from any cause. Overall survival was censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for participants who were lost to follow-up before death was documented.
    Time Frame From randomization until the data cut-off date of 07 September 2012. Maximum time on follow-up for survival was 70 weeks.

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat
    Arm/Group Title Pomalidomide Plus Low-Dose Dexamethasone High-Dose Dexamethasone
    Arm/Group Description Participants received 4 mg pomalidomide administered by mouth on Days 1-21 of each 28-day treatment cycle and 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression. Participants received 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1 through 4, 9 through 12, and 17 through 20 of a 28-day cycle until disease progression.
    Measure Participants 302 153
    Median (95% Confidence Interval) [weeks]
    NA
    34.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pomalidomide Plus Low-Dose Dexamethasone, High-Dose Dexamethasone
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.53
    Confidence Interval (2-Sided) 95%
    0.37 to 0.74
    Parameter Dispersion Type:
    Value:
    Estimation Comments Hazard ratio is for Pomalidomide Plus Low-Dose Dexamethasone : High Dose Dexamethasone
    5. Secondary Outcome
    Title Overall Survival With a Later Cut-off Date
    Description Overall survival is calculated as the time from randomization to death from any cause. Overall survival was censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for participants who were lost to follow-up before death was documented.
    Time Frame From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up for survival was 93 weeks.

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat
    Arm/Group Title Pomalidomide Plus Low-Dose Dexamethasone High-Dose Dexamethasone
    Arm/Group Description Participants received 4 mg pomalidomide administered by mouth on Days 1-21 of each 28-day treatment cycle and 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression. Participants received 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1 through 4, 9 through 12, and 17 through 20 of a 28-day cycle until disease progression.
    Measure Participants 302 153
    Median (95% Confidence Interval) [weeks]
    54.0
    34.9
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pomalidomide Plus Low-Dose Dexamethasone, High-Dose Dexamethasone
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.009
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.70
    Confidence Interval (2-Sided) 95%
    0.54 to 0.92
    Parameter Dispersion Type:
    Value:
    Estimation Comments Hazard ratio is for Pomalidomide Plus Low-Dose Dexamethasone : High Dose Dexamethasone
    6. Secondary Outcome
    Title Overall Survival Based on the Final Dataset
    Description Overall survival is calculated as the time from randomization to death from any cause. Overall survival was censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for participants who were lost to follow-up before death was documented.
    Time Frame From randomization until the data cut-off date of 29 August 2017. Maximum time on follow-up for survival was 324 weeks.

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat
    Arm/Group Title Pomalidomide Plus Low-Dose Dexamethasone High-Dose Dexamethasone
    Arm/Group Description Participants received 4 mg pomalidomide administered by mouth on Days 1-21 of each 28-day treatment cycle and 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression. Participants received 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1 through 4, 9 through 12, and 17 through 20 of a 28-day cycle until disease progression.
    Measure Participants 302 153
    Median (95% Confidence Interval) [weeks]
    56.1
    35.3
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pomalidomide Plus Low-Dose Dexamethasone, High-Dose Dexamethasone
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.005
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.74
    Confidence Interval (2-Sided) 95%
    0.60 to 0.91
    Parameter Dispersion Type:
    Value:
    Estimation Comments Hazard ratio is for Pomalidomide Plus Low-Dose Dexamethasone : High Dose Dexamethasone
    7. Secondary Outcome
    Title Percentage of Participants With an Objective Response According to International Myeloma Working Group (IMWG) Uniform Response Criteria
    Description Objective response is defined as a best overall response of stringent complete response (SCR), complete response (CR), very good partial response (VGPR) or partial response (PR) based on the Independent Response Adjudication Committee: SCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein and urine M-protein level < 100 mg/24 hours; PR: ≥ 50% reduction of serum M-Protein and reduction in urinary M-protein by ≥ 90% or to < 200 mg/24 hours. In addition to the above, if present at baseline a ≥ 50% reduction in the size of soft tissue plasmacytomas is also required.
    Time Frame From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat population
    Arm/Group Title Pomalidomide Plus Low-Dose Dexamethasone High-Dose Dexamethasone
    Arm/Group Description Participants received 4 mg pomalidomide administered by mouth on Days 1-21 of each 28-day treatment cycle and 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression. Participants received 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1 through 4, 9 through 12, and 17 through 20 of a 28-day cycle until disease progression.
    Measure Participants 302 153
    Number [percentage of participants]
    23.5
    7.8%
    3.9
    2.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pomalidomide Plus Low-Dose Dexamethasone, High-Dose Dexamethasone
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments
    Method Fisher Exact
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 7.53
    Confidence Interval (2-Sided) 95%
    3.19 to 17.77
    Parameter Dispersion Type:
    Value:
    Estimation Comments Odds ratio is for pomalidomide plus low-dose dexamethasone : high dose dexamethasone
    8. Secondary Outcome
    Title Percentage of Participants With Objective Response According to European Group for Blood and Marrow Transplantation (EBMT) Criteria
    Description Objective response defined as a best overall response of complete response (CR) or partial response (PR) based on the Independent Response Adjudication Committee: CR requires all of the following: - Absence of original monoclonal paraprotein in serum and urine by immunofixation maintained at least 42 days. - <5% plasma cell in bone marrow aspirate and on bone marrow biopsy, if performed. - No increase in size or number of lytic bone lesions. - Disappearance of soft tissue plasmacytomas. PR requires all of the following: - ≥ 50% reduction in level of serum monoclonal paraprotein, maintained at least 42 days. - Reduction in 24-hour urinary light chain extraction by ≥ 90% or to < 200 mg, maintained at least 42 days. - For patients with non-secretory myeloma, ≥ 50% reduction in plasma cells in bone marrow aspirate and on biopsy, if performed, for at least 42 days. - ≥ 50% reduction in the size of soft tissue plasmacytomas. - No increase in size or number of lytic bone lesions.
    Time Frame From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat population
    Arm/Group Title Pomalidomide Plus Low-Dose Dexamethasone High-Dose Dexamethasone
    Arm/Group Description Participants received 4 mg pomalidomide administered by mouth on Days 1-21 of each 28-day treatment cycle and 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression. Participants received 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1 through 4, 9 through 12, and 17 through 20 of a 28-day cycle until disease progression.
    Measure Participants 302 153
    Number [percentage of participants]
    22.2
    7.4%
    3.3
    2.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pomalidomide Plus Low-Dose Dexamethasone, High-Dose Dexamethasone
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments
    Method Fisher Exact
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 8.44
    Confidence Interval (2-Sided) 95%
    3.32 to 21.42
    Parameter Dispersion Type:
    Value:
    Estimation Comments Odds ratio is for Pomalidomide Plus Low-Dose Dexamethasone : High Dose Dexamethasone
    9. Secondary Outcome
    Title Time to Progression
    Description Time to progression (TTP) is calculated as the time from randomization to the first documented progression confirmed by a blinded, independent Response Adjudication Committee and based on the International Myeloma Working Group Uniform Response criteria (IMWG). Progressive disease requires 1 of the following: • Increase of ≥ 25% from nadir in: o Serum M-component (absolute increase ≥ 0.5 g/dl); o Urine M-component (absolute increase ≥ 200 mg/24 hours); o Bone marrow plasma cell percentage (absolute % ≥ 10%); • Development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas; • Development of hypercalcemia (corrected serum calcium > 11.5 mg/dl) attributed solely to plasma cell proliferative disease.
    Time Frame From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat population
    Arm/Group Title Pomalidomide Plus Low-Dose Dexamethasone High-Dose Dexamethasone
    Arm/Group Description Participants received 4 mg pomalidomide administered by mouth on Days 1-21 of each 28-day treatment cycle and 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression. Participants received 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1 through 4, 9 through 12, and 17 through 20 of a 28-day cycle until disease progression.
    Measure Participants 302 153
    Median (95% Confidence Interval) [weeks]
    20.0
    9.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pomalidomide Plus Low-Dose Dexamethasone, High-Dose Dexamethasone
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments
    Method Stratified Log Rank Test
    Comments Stratified by age, diseases population, and prior number of anti myeloma therapy.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.46
    Confidence Interval (2-Sided) 95%
    0.36 to 0.59
    Parameter Dispersion Type:
    Value:
    Estimation Comments Hazard ratio is for Pomalidomide Plus Low-Dose Dexamethasone : High Dose Dexamethasone
    10. Secondary Outcome
    Title Time to Response
    Description Time to response is calculated as the time from randomization to the initial documented response (partial response or better) based on IMWG criteria. SCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein and urine M-protein level < 100 mg/24 hours; PR: ≥ 50% reduction of serum M-Protein and reduction in urinary M-protein by ≥ 90% or to < 200 mg/24 hours. If present at baseline a ≥ 50% reduction in size of soft tissue plasmacytomas is also required.
    Time Frame From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat responder population
    Arm/Group Title Pomalidomide Plus Low-Dose Dexamethasone High-Dose Dexamethasone
    Arm/Group Description Participants received 4 mg pomalidomide administered by mouth on Days 1-21 of each 28-day treatment cycle and 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression. Participants received 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1 through 4, 9 through 12, and 17 through 20 of a 28-day cycle until disease progression.
    Measure Participants 71 6
    Median (Full Range) [weeks]
    8.1
    10.5
    11. Secondary Outcome
    Title Duration of Response
    Description Duration of response (calculated for responders only) is defined as time from the initial documented response (partial response or better) to confirmed disease progression, based on IMWG criteria assessed by the Independent Response Adjudication Committee.
    Time Frame From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat responder population
    Arm/Group Title Pomalidomide Plus Low-Dose Dexamethasone High-Dose Dexamethasone
    Arm/Group Description Participants received 4 mg pomalidomide administered by mouth on Days 1-21 of each 28-day treatment cycle and 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression. Participants received 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1 through 4, 9 through 12, and 17 through 20 of a 28-day cycle until disease progression.
    Measure Participants 71 6
    Median (95% Confidence Interval) [weeks]
    35.1
    28.1
    12. Secondary Outcome
    Title Time to the First Hemoglobin Improvement
    Description Time to increased hemoglobin, defined as the time from randomization to at least one category improvement from Baseline in common terminology criteria for adverse events (CTCAE) grade for hemoglobin level. Hemoglobin categories are: 1) Normal; 2) CTCAE Grade 1: < lower limit of normal (LLN) to 10.0 g/dL; 3) CTCAE Grade 2: < 10.0 to <8.0 g/dL. Participants with CTCAE Grade 3 anemia or worse at Baseline were excluded from the study.
    Time Frame From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat population with improvement in hemoglobin during the study
    Arm/Group Title Pomalidomide Plus Low-Dose Dexamethasone High-Dose Dexamethasone
    Arm/Group Description Participants received 4 mg pomalidomide administered by mouth on Days 1-21 of each 28-day treatment cycle and 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression. Participants received 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1 through 4, 9 through 12, and 17 through 20 of a 28-day cycle until disease progression.
    Measure Participants 144 50
    Median (Full Range) [weeks]
    3.4
    1.3
    13. Secondary Outcome
    Title Time to Improvement in Bone Pain
    Description Time to improvement in bone pain is defined as the time from randomization to at least one category improvement from Baseline in bone pain category. Bone pain was categorized (from best to worst) according to answers to the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for patients with Multiple Myeloma Module (QLQ-MY20), Question 1, "Have you had bone aches or pain?": 1) Not at all, 2) A little, 3) Quite a bit, or 4) Very much.
    Time Frame From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat population with improvement in bone pain
    Arm/Group Title Pomalidomide Plus Low-Dose Dexamethasone High-Dose Dexamethasone
    Arm/Group Description Participants received 4 mg pomalidomide administered by mouth on Days 1-21 of each 28-day treatment cycle and 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression. Participants received 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1 through 4, 9 through 12, and 17 through 20 of a 28-day cycle until disease progression.
    Measure Participants 101 37
    Median (Full Range) [weeks]
    5.7
    4.1
    14. Secondary Outcome
    Title Time to Improvement in Renal Function
    Description Time to improvement in renal function is defined as the time from randomization to at least one category improvement from Baseline in renal function. Renal Function was categorized as (from best to worst): - Normal: creatinine clearance ≥80 mL/min; - Grade 1: creatinine clearance ≥60 to <80 mL/min; - Grade 2 : creatinine clearance ≥45 to < 60 mL/min. Participants with creatinine clearance < 45 mL/min at baseline were excluded from the study.
    Time Frame From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat population with improvement in renal function
    Arm/Group Title Pomalidomide Plus Low-Dose Dexamethasone High-Dose Dexamethasone
    Arm/Group Description Participants received 4 mg pomalidomide administered by mouth on Days 1-21 of each 28-day treatment cycle and 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression. Participants received 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1 through 4, 9 through 12, and 17 through 20 of a 28-day cycle until disease progression.
    Measure Participants 94 45
    Median (Full Range) [weeks]
    4.6
    4.1
    15. Secondary Outcome
    Title Time to Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status
    Description Time to improvement in ECOG performance status defined as the time from randomization until at least a one category improvement from Baseline in ECOG performance status score. The categories of the ECOG Performance Status Scale are as follows: -0: Fully active, able to carry on all pre-disease performance without restriction; -1: Restricted in physically strenuous activity but ambulatory and able to carry our work of a light or sedentary nature, e.g., light housework, office work; -2: Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours. Patients with a score of 3, 4 or 5 were excluded from participating in the study.
    Time Frame From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat population with improvement in ECOG performance status during the study
    Arm/Group Title Pomalidomide Plus Low-Dose Dexamethasone High-Dose Dexamethasone
    Arm/Group Description Participants received 4 mg pomalidomide administered by mouth on Days 1-21 of each 28-day treatment cycle and 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression. Participants received 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1 through 4, 9 through 12, and 17 through 20 of a 28-day cycle until disease progression.
    Measure Participants 61 18
    Median (Full Range) [weeks]
    8.1
    4.3
    16. Secondary Outcome
    Title Change From Baseline in the European Organization for Research and Treatment of Cancer Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Domain
    Description The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Global Health Status/QOL scale is scored between 0 and 100, with a high score indicating better Global Health Status/QOL. Negative change from Baseline values indicate deterioration in QOL or functioning and positive values indicate improvement.
    Time Frame Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6

    Outcome Measure Data

    Analysis Population Description
    The Patient Reported Outcomes (PRO) study population includes any intent-to-treat study participants with 1 active treatment and 1 PRO measurement item completed. Only participants with available data at Baseline and each time point are included.
    Arm/Group Title Pomalidomide Plus Low-Dose Dexamethasone High-Dose Dexamethasone
    Arm/Group Description Participants received 4 mg pomalidomide administered by mouth on Days 1-21 of each 28-day treatment cycle and 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression. Participants received 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1 through 4, 9 through 12, and 17 through 20 of a 28-day cycle until disease progression.
    Measure Participants 289 144
    Cycle 2, Day 1
    0.52
    (23.01)
    -3.75
    (24.10)
    Cycle 3, Day 1
    2.67
    (24.97)
    -2.36
    (21.08)
    Cycle 4, Day 1
    0.80
    (24.62)
    -3.03
    (22.42)
    Cycle 5 Day 1
    0.51
    (26.81)
    0.00
    (27.44)
    Cycle 6, Day 1
    -2.51
    (25.57)
    -0.93
    (17.59)
    17. Secondary Outcome
    Title Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain
    Description The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Physical Functioning Scale is scored between 0 and 100, with a high score indicating better functioning/support. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.
    Time Frame Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6

    Outcome Measure Data

    Analysis Population Description
    PRO population with available data at Baseline and each time point.
    Arm/Group Title Pomalidomide Plus Low-Dose Dexamethasone High-Dose Dexamethasone
    Arm/Group Description Participants received 4 mg pomalidomide administered by mouth on Days 1-21 of each 28-day treatment cycle and 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression. Participants received 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1 through 4, 9 through 12, and 17 through 20 of a 28-day cycle until disease progression.
    Measure Participants 289 144
    Cycle 2, Day 1
    -2.32
    (18.25)
    -3.96
    (18.35)
    Cycle 3, Day 1
    -0.56
    (19.86)
    -9.69
    (16.67)
    Cycle 4, Day 1
    0.17
    (20.25)
    -8.08
    (13.31)
    Cycle 5 Day 1
    0.91
    (19.92)
    -5.43
    (19.31)
    Cycle 6, Day 1
    0.54
    (21.30)
    -4.81
    (14.24)
    18. Secondary Outcome
    Title Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain
    Description The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Emotional Functioning Scale is scored between 0 and 100, with a high score indicating better functioning/support. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.
    Time Frame Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6

    Outcome Measure Data

    Analysis Population Description
    PRO population with available data at Baseline and each time point.
    Arm/Group Title Pomalidomide Plus Low-Dose Dexamethasone High-Dose Dexamethasone
    Arm/Group Description Participants received 4 mg pomalidomide administered by mouth on Days 1-21 of each 28-day treatment cycle and 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression. Participants received 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1 through 4, 9 through 12, and 17 through 20 of a 28-day cycle until disease progression.
    Measure Participants 289 144
    Cycle 2, Day 1
    1.22
    (21.44)
    -2.87
    (21.57)
    Cycle 3, Day 1
    2.40
    (20.36)
    -5.66
    (25.36)
    Cycle 4, Day 1
    2.44
    (21.05)
    -6.31
    (23.48)
    Cycle 5 Day 1
    1.91
    (21.97)
    -8.64
    (23.17)
    Cycle 6, Day 1
    0.19
    (22.30)
    -4.17
    (13.18)
    19. Secondary Outcome
    Title Change From Baseline in the EORTC QLQ-C30 Fatigue Domain
    Description The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Fatigue Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate reduction in fatigue (i.e. improvement in symptom) and positive values indicate increases in fatigue (i.e. worsening of symptom).
    Time Frame Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6

    Outcome Measure Data

    Analysis Population Description
    PRO population with available data at Baseline and each time point.
    Arm/Group Title Pomalidomide Plus Low-Dose Dexamethasone High-Dose Dexamethasone
    Arm/Group Description Participants received 4 mg pomalidomide administered by mouth on Days 1-21 of each 28-day treatment cycle and 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression. Participants received 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1 through 4, 9 through 12, and 17 through 20 of a 28-day cycle until disease progression.
    Measure Participants 289 144
    Cycle 2, Day 1
    2.43
    (27.39)
    4.03
    (25.37)
    Cycle 3, Day 1
    3.26
    (27.66)
    7.76
    (23.73)
    Cycle 4, Day 1
    1.71
    (26.21)
    9.43
    (28.88)
    Cycle 5 Day 1
    0.21
    (28.41)
    9.47
    (23.00)
    Cycle 6, Day 1
    0.99
    (31.13)
    10.49
    (16.38)
    20. Secondary Outcome
    Title Change From Baseline in the EORTC QLQ-C30 Pain Domain
    Description The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Pain Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate reductions in pain (i.e. improvement in symptom) and positive values indicate increases in pain (i.e. worsening of symptom).
    Time Frame Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6

    Outcome Measure Data

    Analysis Population Description
    PRO population with available data at Baseline and each time point
    Arm/Group Title Pomalidomide Plus Low-Dose Dexamethasone High-Dose Dexamethasone
    Arm/Group Description Participants received 4 mg pomalidomide administered by mouth on Days 1-21 of each 28-day treatment cycle and 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression. Participants received 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1 through 4, 9 through 12, and 17 through 20 of a 28-day cycle until disease progression.
    Measure Participants 289 144
    Cycle 2, Day 1
    -2.70
    (25.74)
    0.36
    (25.32)
    Cycle 3, Day 1
    -3.58
    (29.62)
    2.83
    (25.47)
    Cycle 4, Day 1
    -2.41
    (30.52)
    3.03
    (25.84)
    Cycle 5 Day 1
    -1.64
    (28.00)
    2.47
    (31.59)
    Cycle 6, Day 1
    -2.40
    (30.99)
    10.19
    (23.67)
    21. Secondary Outcome
    Title Change From Baseline in the European Organization for Research and Treatment of Cancer QoL Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms
    Description The European Organization for Research and Treatment of Cancer QoL Questionnaire for Patients with Multiple Myeloma (EORTC QLQ-MY20) is a 20-question tool used in clinical research to assess health-related quality of life in multiple myeloma patients. The QLQ-MY20 includes four domains (Disease Symptoms, Side-Effects of Treatment, Body Image and Future Perspective). The EORTC QLQ-MY20 Disease Symptoms Scale is scored between 0 and 100, with a high score reflecting a higher level of symptoms. Negative change from Baseline values indicate reduction (i.e. improvement) in symptoms and positive values indicate increase (i.e. worsening) of symptoms.
    Time Frame Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6

    Outcome Measure Data

    Analysis Population Description
    PRO population with available data at Baseline and each time point.
    Arm/Group Title Pomalidomide Plus Low-Dose Dexamethasone High-Dose Dexamethasone
    Arm/Group Description Participants received 4 mg pomalidomide administered by mouth on Days 1-21 of each 28-day treatment cycle and 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression. Participants received 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1 through 4, 9 through 12, and 17 through 20 of a 28-day cycle until disease progression.
    Measure Participants 289 144
    Cycle 2, Day 1
    -0.50
    (16.51)
    -1.07
    (17.78)
    Cycle 3, Day 1
    -1.36
    (19.51)
    0.97
    (19.93)
    Cycle 4, Day 1
    -1.15
    (19.54)
    1.35
    (16.94)
    Cycle 5 Day 1
    -0.53
    (17.39)
    1.48
    (17.56)
    Cycle 6, Day 1
    0.60
    (19.64)
    2.12
    (13.43)
    22. Secondary Outcome
    Title Change From Baseline in the EORTC QLQ-MY20 Side Effects Domain
    Description The European Organization for Research and Treatment of Cancer QoL Questionnaire for Patients with Multiple Myeloma (EORTC QLQ-MY20) is a 20-question tool used in clinical research to assess health-related quality of life in multiple myeloma patients. The QLQ-MY20 includes four domains (Disease Symptoms, Side-Effects of Treatment, Body Image and Future Perspective). The EORTC QLQ-MY20 Side Effects Scale is scored between 0 and 100, with a high score reflecting a higher level of symptoms. Negative change from Baseline values indicate reduction in side effects (i.e.improvement in symptom) and positive values indicate increase in side effects (i.e. worsening of symptom).
    Time Frame Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6

    Outcome Measure Data

    Analysis Population Description
    PRO population with available data at Baseline and each time point.
    Arm/Group Title Pomalidomide Plus Low-Dose Dexamethasone High-Dose Dexamethasone
    Arm/Group Description Participants received 4 mg pomalidomide administered by mouth on Days 1-21 of each 28-day treatment cycle and 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression. Participants received 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1 through 4, 9 through 12, and 17 through 20 of a 28-day cycle until disease progression.
    Measure Participants 289 144
    Cycle 2, Day 1
    2.71
    (13.90)
    2.61
    (13.34)
    Cycle 3, Day 1
    3.26
    (13.72)
    5.35
    (12.27)
    Cycle 4, Day 1
    3.73
    (14.47)
    7.46
    (11.61)
    Cycle 5 Day 1
    4.74
    (14.45)
    6.89
    (10.32)
    Cycle 6, Day 1
    4.55
    (15.76)
    7.30
    (9.35)
    23. Secondary Outcome
    Title Change From Baseline in the European Quality of Life-5 Dimensions (EQ-5D) Utility Index Score
    Description EQ-5D is a self-administered questionnaire that assesses health-related quality of life (QOL). The EQ-5D descriptive health profile comprises five dimensions of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Each dimension has 3 levels of response: No problem (1), some problems (2), and extreme problems (3). A unique EQ-5D health state is defined by combining one level from each of the five dimensions into a single utility index score. EQ-5D index values range from -0.59 to 1.00 where an EQ-5D score of 1.00 equals "perfect health", a score of 0 equals "death" and a score of -0.59 equals worst imaginable health state. A positive change from Baseline score indicates improvement in health status. A negative change from Baseline score indicates worsening in health status. Negative scores represent the possible though unlikely situation that a patient's QOL is worse than death, i.e. they would rather be dead than living with that QOL
    Time Frame Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6

    Outcome Measure Data

    Analysis Population Description
    PRO population with available data at Baseline and each time point.
    Arm/Group Title Pomalidomide Plus Low-Dose Dexamethasone High-Dose Dexamethasone
    Arm/Group Description Participants received 4 mg pomalidomide administered by mouth on Days 1-21 of each 28-day treatment cycle and 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression. Participants received 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1 through 4, 9 through 12, and 17 through 20 of a 28-day cycle until disease progression.
    Measure Participants 289 144
    Cycle 2, Day 1
    -0.03
    (0.28)
    -0.02
    (0.23)
    Cycle 3, Day 1
    0.01
    (0.29)
    -0.06
    (0.27)
    Cycle 4, Day 1
    0.04
    (0.31)
    -0.07
    (0.29)
    Cycle 5, Day 1
    0.01
    (0.32)
    -0.04
    (0.26)
    Cycle 6, Day 1
    0.03
    (0.31)
    -0.12
    (0.19)
    24. Secondary Outcome
    Title Time to First Worsening of Quality of Life (QOL) Domains
    Description Time to worsening in quality of life domains was calculated as the time from Baseline to the first worsened minimally important difference (MID), defined as the smallest change in a QOL score considered important to patients that would lead the patient or clinician to consider a change in therapy. MID thresholds were calculated in Standard Error of Measurement (SEM) units using the Baseline QOL data. Based on the MID, participants were classified as worsened according to the following: For the EORTC QLQ-C30 global health status and functional scales and the EQ-5D health utility score, participants were classified as worsened if their change from Baseline score was less than -1 SEM. For the EORTC QLQ-C30 symptom scores (fatigue and pain) and EORTC QLQ-MY20 disease symptoms and side effects scales, participants were classified as worsened if their change from Baseline score was greater than 1 SEM. See previous outcome measures for definitions of each scale.
    Time Frame Assessed on Day 1 of the first 6 treatment cycles.

    Outcome Measure Data

    Analysis Population Description
    PRO population
    Arm/Group Title Pomalidomide Plus Low-Dose Dexamethasone High-Dose Dexamethasone
    Arm/Group Description Participants received 4 mg pomalidomide administered by mouth on Days 1-21 of each 28-day treatment cycle and 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression. Participants received 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1 through 4, 9 through 12, and 17 through 20 of a 28-day cycle until disease progression.
    Measure Participants 289 144
    Global Health Status
    71
    57
    Physical Functioning
    128
    67
    Emotional Functioning
    146
    85
    Fatigue
    58
    57
    Pain
    92
    85
    Disease Symptoms
    127
    106
    Side Effects of Treatment
    90
    85
    Health Utility
    225
    162

    Adverse Events

    Time Frame From first dose of study drug through to 30 days after the last dose as of the end of the study (29 August 2017); maximum time on treatment was 297, 269, and 239 weeks in the Pomalidomide + LD-Dex, HD-Dex, and cross-over groups respectively.
    Adverse Event Reporting Description
    Arm/Group Title Pomalidomide Plus Low-Dose Dexamethasone High-Dose Dexamethasone HD-Dex / Pomalidomide
    Arm/Group Description Participants received 4 mg pomalidomide administered by mouth on Days 1-21 of each 28-day treatment cycle and 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression. Participants received 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1 through 4, 9 through 12, and 17 through 20 of a 28-day cycle until disease progression, or until cross-over to pomalidomide. Data are up to the time of cross-over. Participants initially randomized to high-dose dexamethasone (HD-Dex) crossed over to receive 4 mg pomalidomide administered by mouth on Days 1-21 of each 28-day treatment cycle, with or without low-dose dexamethasone (40 mg for participants ≤ 75 years or 20 mg for participants > 75 years of age, administered orally once per day on Days 1, 8, 15, and 22 of each 28-day cycle) at the discretion of the investigator. Data include AEs that occurred after cross-over to pomalidomide.
    All Cause Mortality
    Pomalidomide Plus Low-Dose Dexamethasone High-Dose Dexamethasone HD-Dex / Pomalidomide
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 252/300 (84%) 124/150 (82.7%) 8/11 (72.7%)
    Serious Adverse Events
    Pomalidomide Plus Low-Dose Dexamethasone High-Dose Dexamethasone HD-Dex / Pomalidomide
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 195/300 (65%) 80/150 (53.3%) 4/11 (36.4%)
    Blood and lymphatic system disorders
    Anaemia 10/300 (3.3%) 7/150 (4.7%) 0/11 (0%)
    Blood disorder 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Febrile neutropenia 19/300 (6.3%) 0/150 (0%) 0/11 (0%)
    Haemorrhagic anaemia 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Hyperviscosity syndrome 1/300 (0.3%) 2/150 (1.3%) 0/11 (0%)
    Neutropenia 10/300 (3.3%) 1/150 (0.7%) 0/11 (0%)
    Pancytopenia 2/300 (0.7%) 2/150 (1.3%) 0/11 (0%)
    Thrombocytopenia 6/300 (2%) 4/150 (2.7%) 0/11 (0%)
    Cardiac disorders
    Angina pectoris 0/300 (0%) 1/150 (0.7%) 0/11 (0%)
    Atrial fibrillation 7/300 (2.3%) 1/150 (0.7%) 0/11 (0%)
    Atrial flutter 1/300 (0.3%) 1/150 (0.7%) 0/11 (0%)
    Atrial tachycardia 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Cardiac amyloidosis 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Cardiac arrest 1/300 (0.3%) 1/150 (0.7%) 1/11 (9.1%)
    Cardiac failure 4/300 (1.3%) 2/150 (1.3%) 0/11 (0%)
    Cardiac failure acute 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Cardiac failure congestive 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Cardio-respiratory arrest 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Ischaemic cardiomyopathy 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Myocardial infarction 2/300 (0.7%) 0/150 (0%) 0/11 (0%)
    Myocardial ischaemia 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Sinus bradycardia 0/300 (0%) 1/150 (0.7%) 0/11 (0%)
    Sinus node dysfunction 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Tachycardia 0/300 (0%) 1/150 (0.7%) 0/11 (0%)
    Ventricular tachycardia 2/300 (0.7%) 0/150 (0%) 0/11 (0%)
    Ear and labyrinth disorders
    Otorrhoea 0/300 (0%) 1/150 (0.7%) 0/11 (0%)
    Eye disorders
    Blepharitis 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Diplopia 2/300 (0.7%) 0/150 (0%) 0/11 (0%)
    Gastrointestinal disorders
    Abdominal pain 2/300 (0.7%) 0/150 (0%) 0/11 (0%)
    Constipation 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Dental caries 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Diarrhoea 2/300 (0.7%) 2/150 (1.3%) 0/11 (0%)
    Enteritis 0/300 (0%) 1/150 (0.7%) 0/11 (0%)
    Gastrointestinal haemorrhage 1/300 (0.3%) 1/150 (0.7%) 0/11 (0%)
    Haemorrhoids 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Incarcerated inguinal hernia 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Large intestine perforation 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Melaena 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Necrotising colitis 0/300 (0%) 1/150 (0.7%) 0/11 (0%)
    Oesophagitis 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Papilla of Vater stenosis 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Retroperitoneal haemorrhage 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Stomatitis 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Vomiting 2/300 (0.7%) 0/150 (0%) 0/11 (0%)
    General disorders
    Adverse drug reaction 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Asthenia 1/300 (0.3%) 2/150 (1.3%) 0/11 (0%)
    Catheter site haemorrhage 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Fatigue 3/300 (1%) 0/150 (0%) 0/11 (0%)
    General physical health deterioration 26/300 (8.7%) 12/150 (8%) 0/11 (0%)
    Hyperthermia 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Malaise 2/300 (0.7%) 0/150 (0%) 0/11 (0%)
    Multiple organ dysfunction syndrome 4/300 (1.3%) 0/150 (0%) 0/11 (0%)
    Non-cardiac chest pain 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Oedema peripheral 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Pain 2/300 (0.7%) 0/150 (0%) 0/11 (0%)
    Performance status decreased 0/300 (0%) 1/150 (0.7%) 0/11 (0%)
    Pyrexia 26/300 (8.7%) 7/150 (4.7%) 0/11 (0%)
    Sudden death 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Hepatobiliary disorders
    Cholestasis 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Gallbladder perforation 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Hepatic mass 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Infections and infestations
    Abscess limb 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Acute sinusitis 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Anal abscess 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Aspergillus infection 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Bacteraemia 2/300 (0.7%) 1/150 (0.7%) 0/11 (0%)
    Bacterial diarrhoea 0/300 (0%) 1/150 (0.7%) 0/11 (0%)
    Bacterial infection 0/300 (0%) 1/150 (0.7%) 0/11 (0%)
    Bacterial sepsis 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Bronchitis 8/300 (2.7%) 1/150 (0.7%) 0/11 (0%)
    Bronchopulmonary aspergillosis 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Cellulitis 2/300 (0.7%) 0/150 (0%) 1/11 (9.1%)
    Conjunctivitis 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Cytomegalovirus chorioretinitis 2/300 (0.7%) 0/150 (0%) 0/11 (0%)
    Device related infection 3/300 (1%) 1/150 (0.7%) 0/11 (0%)
    Device related sepsis 0/300 (0%) 1/150 (0.7%) 0/11 (0%)
    Diverticulitis 0/300 (0%) 1/150 (0.7%) 0/11 (0%)
    Enterobacter infection 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Enterobacter sepsis 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Erysipelas 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Escherichia infection 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Escherichia sepsis 3/300 (1%) 0/150 (0%) 0/11 (0%)
    Escherichia urinary tract infection 1/300 (0.3%) 1/150 (0.7%) 0/11 (0%)
    Gastroenteritis 2/300 (0.7%) 0/150 (0%) 0/11 (0%)
    Gastroenteritis salmonella 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Herpes zoster 2/300 (0.7%) 1/150 (0.7%) 0/11 (0%)
    Infection 3/300 (1%) 1/150 (0.7%) 0/11 (0%)
    Infective exacerbation of chronic obstructive airways disease 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Influenza 2/300 (0.7%) 0/150 (0%) 0/11 (0%)
    Intervertebral discitis 0/300 (0%) 1/150 (0.7%) 0/11 (0%)
    Klebsiella sepsis 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Listeria sepsis 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Lower respiratory tract infection 6/300 (2%) 4/150 (2.7%) 1/11 (9.1%)
    Lung infection 5/300 (1.7%) 1/150 (0.7%) 0/11 (0%)
    Meningitis 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Meningitis cryptococcal 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Neutropenic sepsis 3/300 (1%) 0/150 (0%) 0/11 (0%)
    Ophthalmic herpes simplex 0/300 (0%) 1/150 (0.7%) 0/11 (0%)
    Ophthalmic herpes zoster 0/300 (0%) 1/150 (0.7%) 0/11 (0%)
    Pneumococcal bacteraemia 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Pneumocystis jirovecii pneumonia 3/300 (1%) 1/150 (0.7%) 0/11 (0%)
    Pneumonia 57/300 (19%) 14/150 (9.3%) 2/11 (18.2%)
    Pneumonia bacterial 2/300 (0.7%) 0/150 (0%) 0/11 (0%)
    Pneumonia pneumococcal 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Pneumonia pseudomonal 0/300 (0%) 1/150 (0.7%) 0/11 (0%)
    Pneumonia respiratory syncytial viral 0/300 (0%) 0/150 (0%) 1/11 (9.1%)
    Pneumonia staphylococcal 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Pneumonia streptococcal 1/300 (0.3%) 1/150 (0.7%) 0/11 (0%)
    Progressive multifocal leukoencephalopathy 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Pseudomonal bacteraemia 0/300 (0%) 1/150 (0.7%) 0/11 (0%)
    Pseudomonal sepsis 0/300 (0%) 1/150 (0.7%) 0/11 (0%)
    Respiratory syncytial virus infection 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Respiratory tract infection 4/300 (1.3%) 0/150 (0%) 1/11 (9.1%)
    Salmonella sepsis 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Sepsis 7/300 (2.3%) 3/150 (2%) 0/11 (0%)
    Sepsis syndrome 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Septic arthritis streptococcal 0/300 (0%) 1/150 (0.7%) 0/11 (0%)
    Septic shock 4/300 (1.3%) 6/150 (4%) 0/11 (0%)
    Sialoadenitis 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Sinusitis 2/300 (0.7%) 0/150 (0%) 0/11 (0%)
    Skin infection 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Spinal cord infection 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Streptococcal infection 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Streptococcal sepsis 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Subcutaneous abscess 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Subdural empyema 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Tooth infection 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Upper respiratory tract infection 7/300 (2.3%) 1/150 (0.7%) 0/11 (0%)
    Urinary tract infection 0/300 (0%) 5/150 (3.3%) 0/11 (0%)
    Urosepsis 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Injury, poisoning and procedural complications
    Femoral neck fracture 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Femur fracture 5/300 (1.7%) 1/150 (0.7%) 0/11 (0%)
    Hip fracture 2/300 (0.7%) 0/150 (0%) 0/11 (0%)
    Humerus fracture 2/300 (0.7%) 1/150 (0.7%) 0/11 (0%)
    Lumbar vertebral fracture 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Overdose 1/300 (0.3%) 1/150 (0.7%) 0/11 (0%)
    Pelvic fracture 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Post procedural haematoma 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Rib fracture 1/300 (0.3%) 1/150 (0.7%) 0/11 (0%)
    Spinal compression fracture 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Subdural haematoma 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Investigations
    Blood creatinine increased 1/300 (0.3%) 2/150 (1.3%) 0/11 (0%)
    Blood immunoglobulin M increased 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    C-reactive protein increased 0/300 (0%) 1/150 (0.7%) 0/11 (0%)
    Platelet count decreased 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Metabolism and nutrition disorders
    Cachexia 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Decreased appetite 0/300 (0%) 1/150 (0.7%) 0/11 (0%)
    Dehydration 4/300 (1.3%) 2/150 (1.3%) 0/11 (0%)
    Diabetic ketoacidosis 0/300 (0%) 1/150 (0.7%) 0/11 (0%)
    Hypercalcaemia 13/300 (4.3%) 5/150 (3.3%) 0/11 (0%)
    Hyperglycaemia 2/300 (0.7%) 3/150 (2%) 0/11 (0%)
    Hyperuricaemia 0/300 (0%) 1/150 (0.7%) 0/11 (0%)
    Hypokalaemia 2/300 (0.7%) 1/150 (0.7%) 0/11 (0%)
    Hyponatraemia 4/300 (1.3%) 0/150 (0%) 0/11 (0%)
    Musculoskeletal and connective tissue disorders
    Arthritis reactive 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Back pain 8/300 (2.7%) 2/150 (1.3%) 0/11 (0%)
    Bone pain 10/300 (3.3%) 1/150 (0.7%) 0/11 (0%)
    Groin pain 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Intervertebral disc compression 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Joint swelling 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Muscular weakness 0/300 (0%) 2/150 (1.3%) 0/11 (0%)
    Musculoskeletal chest pain 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Musculoskeletal pain 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Myalgia 0/300 (0%) 1/150 (0.7%) 0/11 (0%)
    Myopathy 0/300 (0%) 1/150 (0.7%) 0/11 (0%)
    Neck pain 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Osteoarthritis 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Osteonecrosis of jaw 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Pain in extremity 2/300 (0.7%) 0/150 (0%) 0/11 (0%)
    Pain in jaw 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Pathological fracture 2/300 (0.7%) 1/150 (0.7%) 0/11 (0%)
    Spinal pain 2/300 (0.7%) 0/150 (0%) 0/11 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma 3/300 (1%) 0/150 (0%) 0/11 (0%)
    Plasma cell leukaemia 1/300 (0.3%) 2/150 (1.3%) 0/11 (0%)
    Plasma cell myeloma 1/300 (0.3%) 1/150 (0.7%) 0/11 (0%)
    Plasmacytoma 3/300 (1%) 1/150 (0.7%) 0/11 (0%)
    Prostate cancer stage IV 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Squamous cell carcinoma of skin 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Tumour pain 0/300 (0%) 1/150 (0.7%) 0/11 (0%)
    Nervous system disorders
    Cerebral haemorrhage 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Cerebrovascular accident 2/300 (0.7%) 1/150 (0.7%) 0/11 (0%)
    Cognitive disorder 1/300 (0.3%) 1/150 (0.7%) 0/11 (0%)
    Coma 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Depressed level of consciousness 2/300 (0.7%) 0/150 (0%) 0/11 (0%)
    Dizziness 1/300 (0.3%) 1/150 (0.7%) 0/11 (0%)
    Dyspraxia 0/300 (0%) 1/150 (0.7%) 0/11 (0%)
    Encephalopathy 0/300 (0%) 1/150 (0.7%) 0/11 (0%)
    Epilepsy 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Headache 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Hemiparesis 0/300 (0%) 1/150 (0.7%) 0/11 (0%)
    Ischaemic cerebral infarction 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Loss of consciousness 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Neurological decompensation 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Parkinson's disease 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Partial seizures 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Post herpetic neuralgia 0/300 (0%) 1/150 (0.7%) 0/11 (0%)
    Presyncope 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Radiculopathy 0/300 (0%) 1/150 (0.7%) 0/11 (0%)
    Seizure 0/300 (0%) 1/150 (0.7%) 0/11 (0%)
    Spinal cord compression 2/300 (0.7%) 1/150 (0.7%) 0/11 (0%)
    Subarachnoid haemorrhage 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Syncope 2/300 (0.7%) 0/150 (0%) 1/11 (9.1%)
    Transient ischaemic attack 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Vertigo CNS origin 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Psychiatric disorders
    Aggression 0/300 (0%) 1/150 (0.7%) 0/11 (0%)
    Bradyphrenia 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Confusional state 3/300 (1%) 3/150 (2%) 0/11 (0%)
    Delirium 0/300 (0%) 1/150 (0.7%) 0/11 (0%)
    Renal and urinary disorders
    Acute kidney injury 11/300 (3.7%) 7/150 (4.7%) 1/11 (9.1%)
    Crush syndrome 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Renal failure 8/300 (2.7%) 1/150 (0.7%) 0/11 (0%)
    Renal impairment 4/300 (1.3%) 2/150 (1.3%) 0/11 (0%)
    Urinary retention 3/300 (1%) 0/150 (0%) 0/11 (0%)
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Atelectasis 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Chronic obstructive pulmonary disease 2/300 (0.7%) 0/150 (0%) 0/11 (0%)
    Cough 2/300 (0.7%) 0/150 (0%) 0/11 (0%)
    Dyspnoea 9/300 (3%) 1/150 (0.7%) 0/11 (0%)
    Epistaxis 3/300 (1%) 2/150 (1.3%) 0/11 (0%)
    Lung disorder 2/300 (0.7%) 1/150 (0.7%) 0/11 (0%)
    Lung infiltration 0/300 (0%) 1/150 (0.7%) 0/11 (0%)
    Oropharyngeal pain 0/300 (0%) 1/150 (0.7%) 0/11 (0%)
    Pneumonitis 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Productive cough 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Pulmonary embolism 5/300 (1.7%) 0/150 (0%) 0/11 (0%)
    Pulmonary oedema 0/300 (0%) 2/150 (1.3%) 0/11 (0%)
    Respiratory failure 3/300 (1%) 0/150 (0%) 0/11 (0%)
    Skin and subcutaneous tissue disorders
    Acute febrile neutrophilic dermatosis 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Vascular disorders
    Axillary vein thrombosis 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Circulatory collapse 0/300 (0%) 1/150 (0.7%) 0/11 (0%)
    Deep vein thrombosis 2/300 (0.7%) 0/150 (0%) 0/11 (0%)
    Hypertension 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Hypertensive crisis 1/300 (0.3%) 0/150 (0%) 0/11 (0%)
    Hypotension 2/300 (0.7%) 0/150 (0%) 0/11 (0%)
    Other (Not Including Serious) Adverse Events
    Pomalidomide Plus Low-Dose Dexamethasone High-Dose Dexamethasone HD-Dex / Pomalidomide
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 291/300 (97%) 143/150 (95.3%) 11/11 (100%)
    Blood and lymphatic system disorders
    Anaemia 159/300 (53%) 77/150 (51.3%) 4/11 (36.4%)
    Leukopenia 40/300 (13.3%) 8/150 (5.3%) 0/11 (0%)
    Lymphopenia 13/300 (4.3%) 8/150 (5.3%) 0/11 (0%)
    Neutropenia 155/300 (51.7%) 30/150 (20%) 5/11 (45.5%)
    Thrombocytopenia 87/300 (29%) 42/150 (28%) 1/11 (9.1%)
    Cardiac disorders
    Palpitations 7/300 (2.3%) 4/150 (2.7%) 1/11 (9.1%)
    Ear and labyrinth disorders
    Ear pain 0/300 (0%) 0/150 (0%) 1/11 (9.1%)
    Endocrine disorders
    Adrenal insufficiency 2/300 (0.7%) 1/150 (0.7%) 1/11 (9.1%)
    Eye disorders
    Cataract 8/300 (2.7%) 4/150 (2.7%) 1/11 (9.1%)
    Macular pigmentation 0/300 (0%) 0/150 (0%) 1/11 (9.1%)
    Gastrointestinal disorders
    Abdominal pain upper 8/300 (2.7%) 3/150 (2%) 1/11 (9.1%)
    Constipation 72/300 (24%) 22/150 (14.7%) 1/11 (9.1%)
    Diarrhoea 73/300 (24.3%) 26/150 (17.3%) 3/11 (27.3%)
    Epigastric discomfort 0/300 (0%) 0/150 (0%) 1/11 (9.1%)
    Mouth ulceration 3/300 (1%) 2/150 (1.3%) 1/11 (9.1%)
    Nausea 57/300 (19%) 16/150 (10.7%) 3/11 (27.3%)
    Parotid gland enlargement 0/300 (0%) 0/150 (0%) 1/11 (9.1%)
    Vomiting 25/300 (8.3%) 6/150 (4%) 1/11 (9.1%)
    General disorders
    Asthenia 53/300 (17.7%) 25/150 (16.7%) 1/11 (9.1%)
    Chest pain 11/300 (3.7%) 4/150 (2.7%) 1/11 (9.1%)
    Chills 18/300 (6%) 2/150 (1.3%) 0/11 (0%)
    Fatigue 103/300 (34.3%) 40/150 (26.7%) 3/11 (27.3%)
    General physical health deterioration 17/300 (5.7%) 5/150 (3.3%) 0/11 (0%)
    Influenza like illness 3/300 (1%) 1/150 (0.7%) 2/11 (18.2%)
    Malaise 10/300 (3.3%) 1/150 (0.7%) 1/11 (9.1%)
    Oedema 9/300 (3%) 7/150 (4.7%) 1/11 (9.1%)
    Oedema peripheral 51/300 (17%) 15/150 (10%) 3/11 (27.3%)
    Pyrexia 74/300 (24.7%) 31/150 (20.7%) 3/11 (27.3%)
    Hepatobiliary disorders
    Cholelithiasis 1/300 (0.3%) 0/150 (0%) 1/11 (9.1%)
    Infections and infestations
    Bronchitis 34/300 (11.3%) 7/150 (4.7%) 1/11 (9.1%)
    Cellulitis 6/300 (2%) 2/150 (1.3%) 1/11 (9.1%)
    Herpes zoster 6/300 (2%) 1/150 (0.7%) 1/11 (9.1%)
    Nasopharyngitis 30/300 (10%) 1/150 (0.7%) 1/11 (9.1%)
    Pneumonia 19/300 (6.3%) 5/150 (3.3%) 0/11 (0%)
    Respiratory tract infection 15/300 (5%) 5/150 (3.3%) 0/11 (0%)
    Sinusitis 10/300 (3.3%) 4/150 (2.7%) 1/11 (9.1%)
    Tooth abscess 1/300 (0.3%) 1/150 (0.7%) 1/11 (9.1%)
    Upper respiratory tract infection 47/300 (15.7%) 10/150 (6.7%) 2/11 (18.2%)
    Urinary tract infection 18/300 (6%) 6/150 (4%) 2/11 (18.2%)
    Wound infection 0/300 (0%) 0/150 (0%) 1/11 (9.1%)
    Injury, poisoning and procedural complications
    Chillblains 0/300 (0%) 0/150 (0%) 1/11 (9.1%)
    Contusion 5/300 (1.7%) 2/150 (1.3%) 1/11 (9.1%)
    Fall 10/300 (3.3%) 4/150 (2.7%) 1/11 (9.1%)
    Jaw fracture 0/300 (0%) 0/150 (0%) 1/11 (9.1%)
    Ligament sprain 0/300 (0%) 0/150 (0%) 1/11 (9.1%)
    Post-traumatic pain 0/300 (0%) 0/150 (0%) 1/11 (9.1%)
    Rib fracture 7/300 (2.3%) 2/150 (1.3%) 1/11 (9.1%)
    Skin abrasion 0/300 (0%) 1/150 (0.7%) 1/11 (9.1%)
    Investigations
    Blood creatinine increased 18/300 (6%) 6/150 (4%) 2/11 (18.2%)
    Blood thyroid stimulating hormone increased 0/300 (0%) 1/150 (0.7%) 1/11 (9.1%)
    Neutrophil count decreased 19/300 (6.3%) 1/150 (0.7%) 1/11 (9.1%)
    Weight decreased 15/300 (5%) 5/150 (3.3%) 2/11 (18.2%)
    White blood cell count decreased 10/300 (3.3%) 1/150 (0.7%) 1/11 (9.1%)
    Metabolism and nutrition disorders
    Decreased appetite 40/300 (13.3%) 10/150 (6.7%) 3/11 (27.3%)
    Dehydration 14/300 (4.7%) 8/150 (5.3%) 0/11 (0%)
    Hypercalcaemia 11/300 (3.7%) 11/150 (7.3%) 0/11 (0%)
    Hyperglycaemia 18/300 (6%) 10/150 (6.7%) 0/11 (0%)
    Hypocalcaemia 14/300 (4.7%) 9/150 (6%) 0/11 (0%)
    Hypokalaemia 31/300 (10.3%) 12/150 (8%) 0/11 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 28/300 (9.3%) 7/150 (4.7%) 0/11 (0%)
    Back pain 59/300 (19.7%) 23/150 (15.3%) 2/11 (18.2%)
    Bone pain 54/300 (18%) 20/150 (13.3%) 2/11 (18.2%)
    Coccydynia 0/300 (0%) 0/150 (0%) 1/11 (9.1%)
    Muscle spasms 47/300 (15.7%) 11/150 (7.3%) 1/11 (9.1%)
    Muscular weakness 11/300 (3.7%) 18/150 (12%) 2/11 (18.2%)
    Musculoskeletal chest pain 12/300 (4%) 3/150 (2%) 1/11 (9.1%)
    Musculoskeletal pain 18/300 (6%) 5/150 (3.3%) 0/11 (0%)
    Myalgia 12/300 (4%) 4/150 (2.7%) 1/11 (9.1%)
    Myopathy 4/300 (1.3%) 11/150 (7.3%) 0/11 (0%)
    Osteolysis 2/300 (0.7%) 0/150 (0%) 1/11 (9.1%)
    Pain in extremity 21/300 (7%) 9/150 (6%) 0/11 (0%)
    Nervous system disorders
    Amnesia 2/300 (0.7%) 0/150 (0%) 1/11 (9.1%)
    Burning sensation 0/300 (0%) 1/150 (0.7%) 1/11 (9.1%)
    Carpal tunnel syndrome 0/300 (0%) 0/150 (0%) 1/11 (9.1%)
    Dizziness 40/300 (13.3%) 13/150 (8.7%) 0/11 (0%)
    Headache 28/300 (9.3%) 9/150 (6%) 1/11 (9.1%)
    Lethargy 9/300 (3%) 4/150 (2.7%) 1/11 (9.1%)
    Neuropathy peripheral 9/300 (3%) 1/150 (0.7%) 1/11 (9.1%)
    Paraesthesia 12/300 (4%) 6/150 (4%) 1/11 (9.1%)
    Peripheral sensory neuropathy 26/300 (8.7%) 4/150 (2.7%) 2/11 (18.2%)
    Tremor 19/300 (6.3%) 2/150 (1.3%) 0/11 (0%)
    Psychiatric disorders
    Agitation 17/300 (5.7%) 7/150 (4.7%) 0/11 (0%)
    Anxiety 15/300 (5%) 9/150 (6%) 0/11 (0%)
    Confusional state 10/300 (3.3%) 7/150 (4.7%) 1/11 (9.1%)
    Delirium 1/300 (0.3%) 0/150 (0%) 1/11 (9.1%)
    Insomnia 36/300 (12%) 32/150 (21.3%) 0/11 (0%)
    Renal and urinary disorders
    Acute kidney injury 5/300 (1.7%) 3/150 (2%) 1/11 (9.1%)
    Nocturia 1/300 (0.3%) 0/150 (0%) 1/11 (9.1%)
    Reproductive system and breast disorders
    Gynaecomastia 0/300 (0%) 0/150 (0%) 1/11 (9.1%)
    Respiratory, thoracic and mediastinal disorders
    Cough 64/300 (21.3%) 15/150 (10%) 1/11 (9.1%)
    Dyspnoea 60/300 (20%) 21/150 (14%) 2/11 (18.2%)
    Dyspnoea exertional 18/300 (6%) 3/150 (2%) 0/11 (0%)
    Epistaxis 26/300 (8.7%) 13/150 (8.7%) 1/11 (9.1%)
    Haemoptysis 0/300 (0%) 2/150 (1.3%) 1/11 (9.1%)
    Productive cough 5/300 (1.7%) 1/150 (0.7%) 1/11 (9.1%)
    Skin and subcutaneous tissue disorders
    Blister 1/300 (0.3%) 0/150 (0%) 1/11 (9.1%)
    Dry skin 8/300 (2.7%) 3/150 (2%) 1/11 (9.1%)
    Erythema 8/300 (2.7%) 2/150 (1.3%) 1/11 (9.1%)
    Hyperhidrosis 18/300 (6%) 1/150 (0.7%) 0/11 (0%)
    Hyperkeratosis 0/300 (0%) 0/150 (0%) 1/11 (9.1%)
    Pruritus 22/300 (7.3%) 4/150 (2.7%) 1/11 (9.1%)
    Rash 25/300 (8.3%) 1/150 (0.7%) 1/11 (9.1%)
    Rash papular 1/300 (0.3%) 0/150 (0%) 1/11 (9.1%)
    Swelling face 2/300 (0.7%) 4/150 (2.7%) 1/11 (9.1%)
    Vascular disorders
    Haematoma 9/300 (3%) 2/150 (1.3%) 1/11 (9.1%)
    Hot flush 2/300 (0.7%) 2/150 (1.3%) 1/11 (9.1%)
    Hypotension 13/300 (4.3%) 4/150 (2.7%) 1/11 (9.1%)
    Thrombophlebitis 1/300 (0.3%) 0/150 (0%) 1/11 (9.1%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Institution may publish the results of its findings if a multicenter publication is not forthcoming within 18 months after study completion. Institution shall provide Celgene with a copy of the papers prior to submission; Celgene shall complete its review within 60 days after receipt. Upon Celgene's request, proposed publication or presentation will be delayed up to 60 additional days to enable Celgene to secure adequate intellectual property protection of patentable material.

    Results Point of Contact

    Name/Title Associate Director, Clinical Trials Disclosure
    Organization Celgene Corporation
    Phone 1-888-260-1599
    Email
    Responsible Party:
    Celgene
    ClinicalTrials.gov Identifier:
    NCT01311687
    Other Study ID Numbers:
    • CC-4047-MM-003
    • 2010-019820-30
    First Posted:
    Mar 9, 2011
    Last Update Posted:
    Oct 24, 2018
    Last Verified:
    Sep 1, 2018