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

Multiple Myeloma Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01311687
• Other study ID #: CC-4047-MM-003
• Secondary ID: 2010-019820-30
• Status: Completed
• Phase: Phase 3
• Start date: March 11, 2011
• Est. completion date: August 29, 2017

Study information

• Verified date: September 2018
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 455
• Est. completion date: August 29, 2017
• Est. primary completion date: March 1, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

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

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Princess Alexandra Hospital	Brisbane
Australia	Royal Prince Alfred Hospital	Camperdown
Australia	Peter MacCallum Cancer Institute	East Melbourne	Victoria
Australia	Frankston Hospital	Frankston	Victoria
Australia	Alfred hospital	Melbourne
Australia	Sir Charles Gairdner Hospital	Nedlands
Australia	Calvary Mater Hospital	Waratah
Australia	Border Medical Oncology	Wodonga
Australia	Wollongong Hospital	Wollongong
Belgium	UZ Gent	Gent
Belgium	UZ Leuven	Leuven
Belgium	CHU UCL Mont-Godinne-Dinant asbl	Yvoir
Canada	Tom Baker Cancer Center	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	James Cancer Hospital	Halifax	Nova Scotia
Canada	Juravinski Cancer Centre	Hamilton	Ontario
Canada	London Health Sciences Centre	London	Ontario
Canada	Maisonneuve Rosemont	Montreal	Quebec
Canada	Royal Victoria Hospital McGill Department of Oncology(RVH)	Montreal	Quebec
Canada	Sir Mortimer B. Davis - Jewish Genl	Montreal	Quebec
Canada	University Health Network	Toronto	Ontario
Canada	British Columbia Cancer Agency	Vancouver	British Columbia
Czechia	Charles University General Hospital	Praha 2
Denmark	Hæmatologisk afd. B Aalborg Sygehus Syd	Aalborg
Denmark	Aarhus University Hospital	Arhus C
Denmark	Odense Universitetshospital	Odense C
Denmark	Vejle Hospital	Vejle
France	CHU d'Angers	Angers Cedex 01
France	Centre Hospitalier de la cote basque	Bayonne
France	Centre Hospitalier Departemental	La Roche sur Yon
France	CHRU de Lille FR	Lille
France	Institut Paoli-Calmettes	Marseille Cedex 9
France	CHRU Nantes	Nantes Cedex 1
France	CHU Hôpital St-Antoine	Paris
France	Hopital Saint-Louis	Paris, Cedex 10
France	CHRU - Hopital du Haut Leveque	Pessac
France	Centre Hospitalier Lyon Sud	Pierre Bénite
France	Hopital Bretonneau	Tours
France	Hopital Purpan	Tulouse Cedex 9
France	CHU Nancy	Vandoeuvre
Germany	Universitatsklinikum Carl Gustav Carus	Dresden
Germany	Universitatsklinikum Essen	Essen
Germany	Askepios Klinik St. Georg	Hamburg
Germany	Universitatsklinikum Heidelberg	Heidelberg
Germany	Universitatsklinikum Jena	Jena
Germany	Universitatsklinikum Leipzig	Leipzig
Germany	University of Tubingen	Tübingen
Germany	Universitatsklinikum Ulm	Ulm
Germany	Universitatsklinikum Wurzburg	Wuerzburg
Greece	Alexandra General Hospital of Athens	Athens
Italy	Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi	Bologna
Italy	Clinica Ematologica- A.O.U. San Martino	Genova
Italy	Oncoematologia, Istituto Nazionale Tumori Fondazione G. Pascale	Napoli
Italy	AOU San Luigi Gonzaga	Orbassano
Italy	Universita degli Studi di Padova	Padova
Italy	Hospital Clinic	Placenza
Italy	Servizio di Ematologia, A.O. - Arcispedale S.Maria Nuova	Reggio Emilia
Italy	Univerita La Sapienza Dipartimento di Biotecnologie Cellulari ed Ematologia	Rome
Italy	Azienda Ospedaliera San Giovanni Battista	Torino
Netherlands	VU University Medical Center	Amsterdam
Netherlands	Erasmus Medical Center	Rotterdam
Netherlands	University Medical Center Utrecht	Utrecht
Russian Federation	State Institution Hematological Research, Centre of Russian Academy of Medical Science	Moscow
Russian Federation	State Institution Moscow Regional Research Clinical Institute	Moscow
Russian Federation	State Educational Institution, Saint Petersburg State Medical University	Saint Petersburg
Russian Federation	St. Petersburg Research Institute of Hematology and Blood Transfusion	St. Petersburg
Spain	Hospital Universitari Germans Trias i Pujol	Badalona (Barcelona)
Spain	Hospital Clinic Provincial de Barcelona	Barcelona
Spain	Hospital 12 de Octubre	Madrid
Spain	Hospital de La Princesa	Madrid
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	Hospital Donostia	San Sebastián (Guipuzcoa)
Spain	Hospital Universitario Marques de Valdecilla	Santander
Spain	Hospital de la Fe	Valencia
Sweden	Department of Hematology Hematology Centre	Göteborg
Sweden	University Hospital in Lund	Lund
Sweden	Karolinska University Hospital	Stockholm
Sweden	Karolinska University Hospital Huddinge	Stockholm
Sweden	Overlakare Medocomcentrum, hematologi	Uppsala
Switzerland	Medizinische Universitatsklinik	Berne
Switzerland	Hopitaux Universitaires de Geneve-HUG	Geneva
Switzerland	UniversitatSspital Zurich	Zürich
United Kingdom	Royal Bournemouth Hospital	Bournemouth
United Kingdom	St James's University Hospital	Leeds
United Kingdom	King's College Hospital	London
United Kingdom	St.Bartholomew's Hospital	London
United Kingdom	Freeman Hospital	Newcastle Upon Tyne
United Kingdom	Nottingham City Hospital	Nottingham
United Kingdom	Derriford Hospital	Plymouth
United Kingdom	Royal Hallamshire HospitalSheffield Teaching Hospitals NHS Trust	Sheffield
United Kingdom	The Royal Marsden Hospital	Sutton-Surrey
United Kingdom	The Royal Wolverhampton Hospital NHS Trust	Wolverhampton
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Czechia,  Denmark,  France,  Germany,  Greece,  Italy,  Netherlands,  Russian Federation,  Spain,  Sweden,  Switzerland,  United Kingdom, 

References & Publications (2)

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, Dimopoul — View 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 M — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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.