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 (NIMBUS)

• ClinicalTrials.gov Identifier: NCT01311687
• Recruitment Status: Completed
• First Posted: March 9, 2011
• Results First Posted: April 30, 2014
• Last Update Posted: October 24, 2018
• Sponsor: Celgene
• Information provided by (Responsible Party): Celgene

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
Multiple Myeloma	Drug: pomalidomide; Drug: Dexamethasone	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• 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: March 11, 2011
• Actual Primary Completion Date: March 1, 2013
• Actual Study Completion Date: August 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 [ 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. ]
   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 [ 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. ]
   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) [ 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. ]
   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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

United States, Minnesota

Mayo Clinic

Rochester, Minnesota, United States, 55905

Australia, South Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia, 5000

Australia, Victoria

Peter MacCallum Cancer Institute

East Melbourne, Victoria, Australia, 3002

Frankston Hospital

Frankston, Victoria, Australia, 3199

Australia

Princess Alexandra Hospital

Brisbane, Australia, QLD4102

Royal Prince Alfred Hospital

Camperdown, Australia, 2050

Alfred hospital

Melbourne, Australia, 3004

Sir Charles Gairdner Hospital

Nedlands, Australia, 6009

Calvary Mater Hospital

Waratah, Australia, NSW 2298

Border Medical Oncology

Wodonga, Australia, 3690

Wollongong Hospital

Wollongong, Australia, 2500

Belgium

UZ Gent

Gent, Belgium, 9000

UZ Leuven

Leuven, Belgium, 3000

CHU UCL Mont-Godinne-Dinant asbl

Yvoir, Belgium, B-5530

Canada, Alberta

Tom Baker Cancer Center

Calgary, Alberta, Canada, T2N 4N2

Cross Cancer Institute

Edmonton, Alberta, Canada, T6G 1Z2

Canada, British Columbia

British Columbia Cancer Agency

Vancouver, British Columbia, Canada, V5Z 4E6

Canada, Nova Scotia

James Cancer Hospital

Halifax, Nova Scotia, Canada, B3H 2Y9

Canada, Ontario

Juravinski Cancer Centre

Hamilton, Ontario, Canada, L8V 5C2

London Health Sciences Centre

London, Ontario, Canada, N6C 6B5

University Health Network

Toronto, Ontario, Canada, M5G 2M9

Canada, Quebec

Maisonneuve Rosemont

Montreal, Quebec, Canada, H1T 2M4

Royal Victoria Hospital McGill Department of Oncology(RVH)

Montreal, Quebec, Canada, H3A 1A1

Sir Mortimer B. Davis - Jewish Genl

Montreal, Quebec, Canada, H3T 1E2

Czechia

Charles University General Hospital

Praha 2, Czechia, 128 08

Denmark

Hæmatologisk afd. B Aalborg Sygehus Syd

Aalborg, Denmark, 9000

Aarhus University Hospital

Arhus C, Denmark, DK-8000

Odense Universitetshospital

Odense C, Denmark, 5000

Vejle Hospital

Vejle, Denmark, 7100

France

CHU d'Angers

Angers Cedex 01, France, 49033

Centre Hospitalier de la cote basque

Bayonne, France, 64109

Centre Hospitalier Departemental

La Roche sur Yon, France, 85025

CHRU de Lille FR

Lille, France, 59037

Institut Paoli-Calmettes

Marseille Cedex 9, France, 13009

CHRU Nantes

Nantes Cedex 1, France, 44093

Hopital Saint-Louis

Paris, Cedex 10, France, 75475

CHU Hôpital St-Antoine

Paris, France, 75571

CHRU - Hopital du Haut Leveque

Pessac, France, 33604

Centre Hospitalier Lyon Sud

Pierre Bénite, France, 69310

Hopital Bretonneau

Tours, France, 37044

Hopital Purpan

Tulouse Cedex 9, France, 31059

CHU Nancy

Vandoeuvre, France, 54511

Germany

Universitatsklinikum Carl Gustav Carus

Dresden, Germany, 01307

Universitatsklinikum Essen

Essen, Germany, 45122

Askepios Klinik St. Georg

Hamburg, Germany, 20099

Universitatsklinikum Heidelberg

Heidelberg, Germany, 69120

Universitatsklinikum Jena

Jena, Germany, 07740

Universitatsklinikum Leipzig

Leipzig, Germany, 04103

University of Tubingen

Tübingen, Germany, 72076

Universitatsklinikum Ulm

Ulm, Germany, 89081

Universitatsklinikum Wurzburg

Wuerzburg, Germany, 97080

Greece

Alexandra General Hospital of Athens

Athens, Greece, 11528

Italy

Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi

Bologna, Italy, 40138

Clinica Ematologica- A.O.U. San Martino

Genova, Italy, 16132

Oncoematologia, Istituto Nazionale Tumori Fondazione G. Pascale

Napoli, Italy, 80131

AOU San Luigi Gonzaga

Orbassano, Italy, 10043

Universita degli Studi di Padova

Padova, Italy, 35128

Hospital Clinic

Placenza, Italy, 29100

Servizio di Ematologia, A.O. - Arcispedale S.Maria Nuova

Reggio Emilia, Italy, 42100

Univerita La Sapienza Dipartimento di Biotecnologie Cellulari ed Ematologia

Rome, Italy, 00161

Azienda Ospedaliera San Giovanni Battista

Torino, Italy, 10126

Netherlands

VU University Medical Center

Amsterdam, Netherlands, 1081 HV

Erasmus Medical Center

Rotterdam, Netherlands, 3015 CE

University Medical Center Utrecht

Utrecht, Netherlands, 3584 CX

Russian Federation

State Institution Hematological Research, Centre of Russian Academy of Medical Science

Moscow, Russian Federation, 125167

State Institution Moscow Regional Research Clinical Institute

Moscow, Russian Federation, 125284

State Educational Institution, Saint Petersburg State Medical University

Saint Petersburg, Russian Federation, 197022

St. Petersburg Research Institute of Hematology and Blood Transfusion

St. Petersburg, Russian Federation, 191024

Spain

Hospital Universitari Germans Trias i Pujol

Badalona (Barcelona), Spain, 08916

Hospital Clinic Provincial de Barcelona

Barcelona, Spain, 08036

Hospital de La Princesa

Madrid, Spain, 28006

Hospital 12 de Octubre

Madrid, Spain, 28041

Hospital Universitario de Salamanca

Salamanca, Spain, 37007

Hospital Donostia

San Sebastián (Guipuzcoa), Spain, 20014

Hospital Universitario Marques de Valdecilla

Santander, Spain, 39008

Hospital de la Fe

Valencia, Spain, 46009

Sweden

Department of Hematology Hematology Centre

Göteborg, Sweden, S-413 45

University Hospital in Lund

Lund, Sweden, 221 85

Karolinska University Hospital Huddinge

Stockholm, Sweden, SE 17176

Karolinska University Hospital

Stockholm, Sweden, SE-171 76

Overlakare Medocomcentrum, hematologi

Uppsala, Sweden, 75185

Switzerland

Medizinische Universitatsklinik

Berne, Switzerland, CH - 3010

Hopitaux Universitaires de Geneve-HUG

Geneva, Switzerland, 1205

UniversitatSspital Zurich

Zürich, Switzerland, 8091

United Kingdom

Royal Bournemouth Hospital

Bournemouth, United Kingdom, BH7 7DW

St James's University Hospital

Leeds, United Kingdom, LS9 7TF

St.Bartholomew's Hospital

London, United Kingdom, EC1A 7BE

King's College Hospital

London, United Kingdom, SE5 9RS

Freeman Hospital

Newcastle Upon Tyne, United Kingdom, NE7 7DN

Nottingham City Hospital

Nottingham, United Kingdom, NG5 1PB

Derriford Hospital

Plymouth, United Kingdom, PL6 8DH

Royal Hallamshire HospitalSheffield Teaching Hospitals NHS Trust

Sheffield, United Kingdom, S10 2JF

The Royal Marsden Hospital

Sutton-Surrey, United Kingdom, SM2 5PT

The Royal Wolverhampton Hospital NHS Trust

Wolverhampton, United Kingdom, WV10 0QP

Sponsors and Collaborators

Celgene

Investigators

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

More Information

Publications of Results:

Moreau P, Weisel KC, Song KW, Gibson CJ, Saunders O, Sternas LA, Hong K, Zaki MH, Dimopoulos MA. Relationship of response and survival in patients with relapsed and refractory multiple myeloma treated with pomalidomide plus low-dose dexamethasone in the MM-003 trial randomized phase III trial (NIMBUS). Leuk Lymphoma. 2016 Dec;57(12):2839-2847. doi: 10.1080/10428194.2016.1180685. Epub 2016 May 13.

Miguel JS, Weisel K, Moreau P, Lacy M, Song K, Delforge M, Karlin L, Goldschmidt H, Banos A, Oriol A, Alegre A, Chen C, Cavo M, Garderet L, Ivanova V, Martinez-Lopez J, Belch A, Palumbo A, Schey S, Sonneveld P, Yu X, Sternas L, Jacques C, Zaki M, Dimopoulos M. Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial. Lancet Oncol. 2013 Oct;14(11):1055-1066. doi: 10.1016/S1470-2045(13)70380-2. Epub 2013 Sep 3.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Siegel DS, Weisel KC, Dimopoulos MA, Baz R, Richardson P, Delforge M, Song KW, San Miguel JF, Moreau P, Goldschmidt H, Cavo M, Jagannath S, Yu X, Hong K, Sternas L, Zaki M, Palumbo A. Pomalidomide plus low-dose dexamethasone in patients with relapsed/refractory multiple myeloma and moderate renal impairment: a pooled analysis of three clinical trials. Leuk Lymphoma. 2016 Dec;57(12):2833-2838. doi: 10.1080/10428194.2016.1177181. Epub 2016 Jun 7.

Weisel KC, Dimopoulos MA, Moreau P, Lacy MQ, Song KW, Delforge M, Karlin L, Goldschmidt H, Banos A, Oriol A, Alegre A, Chen C, Cavo M, Garderet L, Ivanova V, Martinez-Lopez J, Knop S, Yu X, Hong K, Sternas L, Jacques C, Zaki MH, San Miguel J. Analysis of renal impairment in MM-003, a phase III study of pomalidomide + low - dose dexamethasone versus high - dose dexamethasone in refractory or relapsed and refractory multiple myeloma. Haematologica. 2016 Jul;101(7):872-8. doi: 10.3324/haematol.2015.137083. Epub 2016 Apr 14.

Dimopoulos MA, Weisel KC, Song KW, Delforge M, Karlin L, Goldschmidt H, Moreau P, Banos A, Oriol A, Garderet L, Cavo M, Ivanova V, Alegre A, Martinez-Lopez J, Chen C, Spencer A, Knop S, Bahlis NJ, Renner C, Yu X, Hong K, Sternas L, Jacques C, Zaki MH, San Miguel JF. Cytogenetics and long-term survival of patients with refractory or relapsed and refractory multiple myeloma treated with pomalidomide and low-dose dexamethasone. Haematologica. 2015 Oct;100(10):1327-33. doi: 10.3324/haematol.2014.117077. Epub 2015 Aug 6.

San Miguel JF, Weisel KC, Song KW, Delforge M, Karlin L, Goldschmidt H, Moreau P, Banos A, Oriol A, Garderet L, Cavo M, Ivanova V, Alegre A, Martinez-Lopez J, Chen C, Renner C, Bahlis NJ, Yu X, Teasdale T, Sternas L, Jacques C, Zaki MH, Dimopoulos MA. Impact of prior treatment and depth of response on survival in MM-003, a randomized phase 3 study comparing pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone in relapsed/refractory multiple myeloma. Haematologica. 2015 Oct;100(10):1334-9. doi: 10.3324/haematol.2015.125864. Epub 2015 Jul 9.

Weisel K, Dimopoulos M, Song KW, Moreau P, Palumbo A, Belch A, Schey S, Sonneveld P, Sternas L, Yu X, Amatya R, Gibson CJ, Zaki M, Jacques C, San Miguel J. Pomalidomide and Low-Dose Dexamethasone Improves Health-Related Quality of Life and Prolongs Time to Worsening in Relapsed/Refractory Patients With Multiple Myeloma Enrolled in the MM-003 Randomized Phase III Trial. Clin Lymphoma Myeloma Leuk. 2015 Sep;15(9):519-30. doi: 10.1016/j.clml.2015.05.007. Epub 2015 Jun 6.

Song KW, Dimopoulos MA, Weisel KC, Moreau P, Palumbo A, Belch A, Schey S, Sonneveld P, Sternas L, Yu X, Amatya R, Monzini MS, Zaki M, Jacques C, San Miguel J. Health-related quality of life from the MM-003 trial of pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone in relapsed and/or refractory multiple myeloma. Haematologica. 2015 Feb;100(2):e63-7. doi: 10.3324/haematol.2014.112557. Epub 2014 Nov 25. No abstract available.

• Responsible Party: Celgene
• ClinicalTrials.gov Identifier: NCT01311687
• Other Study ID Numbers: CC-4047-MM-003; 2010-019820-30 ( EudraCT Number )
• First Posted: March 9, 2011
• Results First Posted: April 30, 2014
• Last Update Posted: October 24, 2018
• Last Verified: September 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; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Dexamethasone; Pomalidomide; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents