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)

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

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.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: pomalidomide; Drug: Dexamethasone

• Study Type: Interventional
• Enrollment (Actual): 455
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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 (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.	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 Measures

Outcome Measure	Measure Description	Time Frame
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.	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.
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.	From randomization until the data cut-off date of 07 September 2012. Maximum time on follow-up for survival was 70 weeks.
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.	From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up for survival was 93 weeks.
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.	From randomization until the data cut-off date of 29 August 2017. Maximum time on follow-up for survival was 324 weeks.
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.	From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.
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.	From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.
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.	From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.
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.	From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.
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.	From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.
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.	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	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.	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	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.	From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.
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.	From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.
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.	Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6
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.	Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6
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.	Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6
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).	Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6
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).	Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6
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.	Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6
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).	Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6
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	Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6
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.	Assessed on Day 1 of the first 6 treatment cycles.

Collaborators and Investigators

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

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 11, 2011
• Primary Completion (ACTUAL): March 1, 2013
• Study Completion (ACTUAL): August 29, 2017

Study Registration Dates

• First Submitted: March 8, 2011
• First Submitted That Met QC Criteria: March 8, 2011
• First Posted (ESTIMATE): March 9, 2011

Study Record Updates

• Last Update Posted (ACTUAL): October 24, 2018
• Last Update Submitted That Met QC Criteria: September 25, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: Pomalidomide; Multiple Myeloma; Myeloma; Relapsed Multiple Myeloma; Refractory Myeloma; Relapsed and Refractory Multiple Myeloma; Resistant Multiple Myeloma; Treatment-resistant Multiple Myeloma; Lenalidomide-resistant; Bortezomib-resistant
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Dexamethasone; Pomalidomide
• Other Study ID Numbers: CC-4047-MM-003; 2010-019820-30 (EUDRACT_NUMBER)