search
Back to results

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)

Primary Purpose

Multiple Myeloma

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
pomalidomide
Dexamethasone
Sponsored by
Celgene
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Mayo Clinic
  • Royal Adelaide Hospital
  • Peter MacCallum Cancer Institute
  • Frankston Hospital
  • Princess Alexandra Hospital
  • Royal Prince Alfred Hospital
  • Alfred hospital
  • Sir Charles Gairdner Hospital
  • Calvary Mater Hospital
  • Border Medical Oncology
  • Wollongong Hospital
  • UZ Gent
  • UZ Leuven
  • CHU UCL Mont-Godinne-Dinant asbl
  • Tom Baker Cancer Center
  • Cross Cancer Institute
  • British Columbia Cancer Agency
  • James Cancer Hospital
  • Juravinski Cancer Centre
  • London Health Sciences Centre
  • University Health Network
  • Maisonneuve Rosemont
  • Royal Victoria Hospital McGill Department of Oncology(RVH)
  • Sir Mortimer B. Davis - Jewish Genl
  • Charles University General Hospital
  • Hæmatologisk afd. B Aalborg Sygehus Syd
  • Aarhus University Hospital
  • Odense Universitetshospital
  • Vejle Hospital
  • CHU d'Angers
  • Centre Hospitalier de la cote basque
  • Centre Hospitalier Departemental
  • CHRU de Lille FR
  • Institut Paoli-Calmettes
  • CHRU Nantes
  • Hopital Saint-Louis
  • CHU Hôpital St-Antoine
  • CHRU - Hopital du Haut Leveque
  • Centre Hospitalier Lyon Sud
  • Hopital Bretonneau
  • Hopital Purpan
  • CHU Nancy
  • Universitatsklinikum Carl Gustav Carus
  • Universitatsklinikum Essen
  • Askepios Klinik St. Georg
  • Universitatsklinikum Heidelberg
  • Universitatsklinikum Jena
  • Universitatsklinikum Leipzig
  • University of Tubingen
  • Universitatsklinikum Ulm
  • Universitatsklinikum Wurzburg
  • Alexandra General Hospital of Athens
  • Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi
  • Clinica Ematologica- A.O.U. San Martino
  • Oncoematologia, Istituto Nazionale Tumori Fondazione G. Pascale
  • AOU San Luigi Gonzaga
  • Universita degli Studi di Padova
  • Hospital Clinic
  • Servizio di Ematologia, A.O. - Arcispedale S.Maria Nuova
  • Univerita La Sapienza Dipartimento di Biotecnologie Cellulari ed Ematologia
  • Azienda Ospedaliera San Giovanni Battista
  • VU University Medical Center
  • Erasmus Medical Center
  • University Medical Center Utrecht
  • State Institution Hematological Research, Centre of Russian Academy of Medical Science
  • State Institution Moscow Regional Research Clinical Institute
  • State Educational Institution, Saint Petersburg State Medical University
  • St. Petersburg Research Institute of Hematology and Blood Transfusion
  • Hospital Universitari Germans Trias i Pujol
  • Hospital Clinic Provincial de Barcelona
  • Hospital de La Princesa
  • Hospital 12 de Octubre
  • Hospital Universitario de Salamanca
  • Hospital Donostia
  • Hospital Universitario Marques de Valdecilla
  • Hospital de la Fe
  • Department of Hematology Hematology Centre
  • University Hospital in Lund
  • Karolinska University Hospital Huddinge
  • Karolinska University Hospital
  • Overlakare Medocomcentrum, hematologi
  • Medizinische Universitatsklinik
  • Hopitaux Universitaires de Geneve-HUG
  • UniversitatSspital Zurich
  • Royal Bournemouth Hospital
  • St James's University Hospital
  • St.Bartholomew's Hospital
  • King's College Hospital
  • Freeman Hospital
  • Nottingham City Hospital
  • Derriford Hospital
  • Royal Hallamshire HospitalSheffield Teaching Hospitals NHS Trust
  • The Royal Marsden Hospital
  • The Royal Wolverhampton Hospital NHS Trust

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Pomalidomide + Low-Dose Dexamethasone

High-Dose Dexamethasone

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Progression-free Survival (PFS) - Primary Analysis
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.
Progression-free Survival (PFS) With a Later Cut-off Date
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

Number of Participants With Adverse Events (AEs)
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.
Overall Survival - Primary Analysis
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.
Overall Survival With a Later Cut-off Date
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.
Overall Survival Based on the Final Dataset
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.
Percentage of Participants With an Objective Response According to International Myeloma Working Group (IMWG) Uniform Response Criteria
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.
Percentage of Participants With Objective Response According to European Group for Blood and Marrow Transplantation (EBMT) Criteria
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 to Progression
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 to Response
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.
Duration of Response
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 to the First Hemoglobin Improvement
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 to Improvement in Bone Pain
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 to Improvement in Renal Function
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 to Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status
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.
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
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.
Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain
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.
Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain
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.
Change From Baseline in the EORTC QLQ-C30 Fatigue Domain
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).
Change From Baseline in the EORTC QLQ-C30 Pain Domain
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).
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
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.
Change From Baseline in the EORTC QLQ-MY20 Side Effects Domain
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).
Change From Baseline in the European Quality of Life-5 Dimensions (EQ-5D) Utility Index Score
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 to First Worsening of Quality of Life (QOL) Domains
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.

Full Information

First Posted
March 8, 2011
Last Updated
September 25, 2018
Sponsor
Celgene
search

1. Study Identification

Unique Protocol Identification Number
NCT01311687
Brief Title
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
Acronym
NIMBUS
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2018
Overall Recruitment Status
Completed
Study Start Date
March 11, 2011 (Actual)
Primary Completion Date
March 1, 2013 (Actual)
Study Completion Date
August 29, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Celgene

4. Oversight

Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
455 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Pomalidomide + Low-Dose Dexamethasone
Arm Type
Experimental
Arm Description
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.
Arm Title
High-Dose Dexamethasone
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
pomalidomide
Other Intervention Name(s)
CC-4047, Pomalyst®
Intervention Description
4 mg pomalidomide capsules administered orally
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
40 mg dexamethasone (or 20 mg for participants > 75 years of age) tablets administered orally
Primary Outcome Measure Information:
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.
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.
Secondary Outcome Measure Information:
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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
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
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
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
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
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
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
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
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.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lars Sternas, MD, PhD
Organizational Affiliation
Celgene
Official's Role
Study Director
Facility Information:
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Royal Adelaide Hospital
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Facility Name
Peter MacCallum Cancer Institute
City
East Melbourne
State/Province
Victoria
ZIP/Postal Code
3002
Country
Australia
Facility Name
Frankston Hospital
City
Frankston
State/Province
Victoria
ZIP/Postal Code
3199
Country
Australia
Facility Name
Princess Alexandra Hospital
City
Brisbane
ZIP/Postal Code
QLD4102
Country
Australia
Facility Name
Royal Prince Alfred Hospital
City
Camperdown
ZIP/Postal Code
2050
Country
Australia
Facility Name
Alfred hospital
City
Melbourne
ZIP/Postal Code
3004
Country
Australia
Facility Name
Sir Charles Gairdner Hospital
City
Nedlands
ZIP/Postal Code
6009
Country
Australia
Facility Name
Calvary Mater Hospital
City
Waratah
ZIP/Postal Code
NSW 2298
Country
Australia
Facility Name
Border Medical Oncology
City
Wodonga
ZIP/Postal Code
3690
Country
Australia
Facility Name
Wollongong Hospital
City
Wollongong
ZIP/Postal Code
2500
Country
Australia
Facility Name
UZ Gent
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
UZ Leuven
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
CHU UCL Mont-Godinne-Dinant asbl
City
Yvoir
ZIP/Postal Code
B-5530
Country
Belgium
Facility Name
Tom Baker Cancer Center
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4N2
Country
Canada
Facility Name
Cross Cancer Institute
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 1Z2
Country
Canada
Facility Name
British Columbia Cancer Agency
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 4E6
Country
Canada
Facility Name
James Cancer Hospital
City
Halifax
State/Province
Nova Scotia
ZIP/Postal Code
B3H 2Y9
Country
Canada
Facility Name
Juravinski Cancer Centre
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8V 5C2
Country
Canada
Facility Name
London Health Sciences Centre
City
London
State/Province
Ontario
ZIP/Postal Code
N6C 6B5
Country
Canada
Facility Name
University Health Network
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
Maisonneuve Rosemont
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H1T 2M4
Country
Canada
Facility Name
Royal Victoria Hospital McGill Department of Oncology(RVH)
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3A 1A1
Country
Canada
Facility Name
Sir Mortimer B. Davis - Jewish Genl
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1E2
Country
Canada
Facility Name
Charles University General Hospital
City
Praha 2
ZIP/Postal Code
128 08
Country
Czechia
Facility Name
Hæmatologisk afd. B Aalborg Sygehus Syd
City
Aalborg
ZIP/Postal Code
9000
Country
Denmark
Facility Name
Aarhus University Hospital
City
Arhus C
ZIP/Postal Code
DK-8000
Country
Denmark
Facility Name
Odense Universitetshospital
City
Odense C
ZIP/Postal Code
5000
Country
Denmark
Facility Name
Vejle Hospital
City
Vejle
ZIP/Postal Code
7100
Country
Denmark
Facility Name
CHU d'Angers
City
Angers Cedex 01
ZIP/Postal Code
49033
Country
France
Facility Name
Centre Hospitalier de la cote basque
City
Bayonne
ZIP/Postal Code
64109
Country
France
Facility Name
Centre Hospitalier Departemental
City
La Roche sur Yon
ZIP/Postal Code
85025
Country
France
Facility Name
CHRU de Lille FR
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
Institut Paoli-Calmettes
City
Marseille Cedex 9
ZIP/Postal Code
13009
Country
France
Facility Name
CHRU Nantes
City
Nantes Cedex 1
ZIP/Postal Code
44093
Country
France
Facility Name
Hopital Saint-Louis
City
Paris, Cedex 10
ZIP/Postal Code
75475
Country
France
Facility Name
CHU Hôpital St-Antoine
City
Paris
ZIP/Postal Code
75571
Country
France
Facility Name
CHRU - Hopital du Haut Leveque
City
Pessac
ZIP/Postal Code
33604
Country
France
Facility Name
Centre Hospitalier Lyon Sud
City
Pierre Bénite
ZIP/Postal Code
69310
Country
France
Facility Name
Hopital Bretonneau
City
Tours
ZIP/Postal Code
37044
Country
France
Facility Name
Hopital Purpan
City
Tulouse Cedex 9
ZIP/Postal Code
31059
Country
France
Facility Name
CHU Nancy
City
Vandoeuvre
ZIP/Postal Code
54511
Country
France
Facility Name
Universitatsklinikum Carl Gustav Carus
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
Universitatsklinikum Essen
City
Essen
ZIP/Postal Code
45122
Country
Germany
Facility Name
Askepios Klinik St. Georg
City
Hamburg
ZIP/Postal Code
20099
Country
Germany
Facility Name
Universitatsklinikum Heidelberg
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Universitatsklinikum Jena
City
Jena
ZIP/Postal Code
07740
Country
Germany
Facility Name
Universitatsklinikum Leipzig
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Facility Name
University of Tubingen
City
Tübingen
ZIP/Postal Code
72076
Country
Germany
Facility Name
Universitatsklinikum Ulm
City
Ulm
ZIP/Postal Code
89081
Country
Germany
Facility Name
Universitatsklinikum Wurzburg
City
Wuerzburg
ZIP/Postal Code
97080
Country
Germany
Facility Name
Alexandra General Hospital of Athens
City
Athens
ZIP/Postal Code
11528
Country
Greece
Facility Name
Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi
City
Bologna
ZIP/Postal Code
40138
Country
Italy
Facility Name
Clinica Ematologica- A.O.U. San Martino
City
Genova
ZIP/Postal Code
16132
Country
Italy
Facility Name
Oncoematologia, Istituto Nazionale Tumori Fondazione G. Pascale
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Facility Name
AOU San Luigi Gonzaga
City
Orbassano
ZIP/Postal Code
10043
Country
Italy
Facility Name
Universita degli Studi di Padova
City
Padova
ZIP/Postal Code
35128
Country
Italy
Facility Name
Hospital Clinic
City
Placenza
ZIP/Postal Code
29100
Country
Italy
Facility Name
Servizio di Ematologia, A.O. - Arcispedale S.Maria Nuova
City
Reggio Emilia
ZIP/Postal Code
42100
Country
Italy
Facility Name
Univerita La Sapienza Dipartimento di Biotecnologie Cellulari ed Ematologia
City
Rome
ZIP/Postal Code
00161
Country
Italy
Facility Name
Azienda Ospedaliera San Giovanni Battista
City
Torino
ZIP/Postal Code
10126
Country
Italy
Facility Name
VU University Medical Center
City
Amsterdam
ZIP/Postal Code
1081 HV
Country
Netherlands
Facility Name
Erasmus Medical Center
City
Rotterdam
ZIP/Postal Code
3015 CE
Country
Netherlands
Facility Name
University Medical Center Utrecht
City
Utrecht
ZIP/Postal Code
3584 CX
Country
Netherlands
Facility Name
State Institution Hematological Research, Centre of Russian Academy of Medical Science
City
Moscow
ZIP/Postal Code
125167
Country
Russian Federation
Facility Name
State Institution Moscow Regional Research Clinical Institute
City
Moscow
ZIP/Postal Code
125284
Country
Russian Federation
Facility Name
State Educational Institution, Saint Petersburg State Medical University
City
Saint Petersburg
ZIP/Postal Code
197022
Country
Russian Federation
Facility Name
St. Petersburg Research Institute of Hematology and Blood Transfusion
City
St. Petersburg
ZIP/Postal Code
191024
Country
Russian Federation
Facility Name
Hospital Universitari Germans Trias i Pujol
City
Badalona (Barcelona)
ZIP/Postal Code
08916
Country
Spain
Facility Name
Hospital Clinic Provincial de Barcelona
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Hospital de La Princesa
City
Madrid
ZIP/Postal Code
28006
Country
Spain
Facility Name
Hospital 12 de Octubre
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Hospital Universitario de Salamanca
City
Salamanca
ZIP/Postal Code
37007
Country
Spain
Facility Name
Hospital Donostia
City
San Sebastián (Guipuzcoa)
ZIP/Postal Code
20014
Country
Spain
Facility Name
Hospital Universitario Marques de Valdecilla
City
Santander
ZIP/Postal Code
39008
Country
Spain
Facility Name
Hospital de la Fe
City
Valencia
ZIP/Postal Code
46009
Country
Spain
Facility Name
Department of Hematology Hematology Centre
City
Göteborg
ZIP/Postal Code
S-413 45
Country
Sweden
Facility Name
University Hospital in Lund
City
Lund
ZIP/Postal Code
221 85
Country
Sweden
Facility Name
Karolinska University Hospital Huddinge
City
Stockholm
ZIP/Postal Code
SE 17176
Country
Sweden
Facility Name
Karolinska University Hospital
City
Stockholm
ZIP/Postal Code
SE-171 76
Country
Sweden
Facility Name
Overlakare Medocomcentrum, hematologi
City
Uppsala
ZIP/Postal Code
75185
Country
Sweden
Facility Name
Medizinische Universitatsklinik
City
Berne
ZIP/Postal Code
CH - 3010
Country
Switzerland
Facility Name
Hopitaux Universitaires de Geneve-HUG
City
Geneva
ZIP/Postal Code
1205
Country
Switzerland
Facility Name
UniversitatSspital Zurich
City
Zürich
ZIP/Postal Code
8091
Country
Switzerland
Facility Name
Royal Bournemouth Hospital
City
Bournemouth
ZIP/Postal Code
BH7 7DW
Country
United Kingdom
Facility Name
St James's University Hospital
City
Leeds
ZIP/Postal Code
LS9 7TF
Country
United Kingdom
Facility Name
St.Bartholomew's Hospital
City
London
ZIP/Postal Code
EC1A 7BE
Country
United Kingdom
Facility Name
King's College Hospital
City
London
ZIP/Postal Code
SE5 9RS
Country
United Kingdom
Facility Name
Freeman Hospital
City
Newcastle Upon Tyne
ZIP/Postal Code
NE7 7DN
Country
United Kingdom
Facility Name
Nottingham City Hospital
City
Nottingham
ZIP/Postal Code
NG5 1PB
Country
United Kingdom
Facility Name
Derriford Hospital
City
Plymouth
ZIP/Postal Code
PL6 8DH
Country
United Kingdom
Facility Name
Royal Hallamshire HospitalSheffield Teaching Hospitals NHS Trust
City
Sheffield
ZIP/Postal Code
S10 2JF
Country
United Kingdom
Facility Name
The Royal Marsden Hospital
City
Sutton-Surrey
ZIP/Postal Code
SM2 5PT
Country
United Kingdom
Facility Name
The Royal Wolverhampton Hospital NHS Trust
City
Wolverhampton
ZIP/Postal Code
WV10 0QP
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
27173785
Citation
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.
Results Reference
result
PubMed Identifier
24007748
Citation
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.
Results Reference
result
PubMed Identifier
27267105
Citation
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.
Results Reference
derived
PubMed Identifier
27081177
Citation
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.
Results Reference
derived
PubMed Identifier
26250580
Citation
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.
Results Reference
derived
PubMed Identifier
26160879
Citation
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.
Results Reference
derived
PubMed Identifier
26149712
Citation
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.
Results Reference
derived
PubMed Identifier
25425684
Citation
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.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs