A Study to Compare MPR With MP in Newly Diagnosed Multiple Myeloma Subjects 65 Years Old or Older.

Newly Diagnosed Multiple Myeloma Clinical Trial

Official title:

A PHASE III, MULTICENTRE, RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED, 3-ARM PARALLEL GROUP STUDY TO DETERMINE THE EFFICACY AND SAFETY OF LENALIDOMIDE (REVLIMID¿) IN COMBINATION WITH MELPHALAN AND PREDNISONE VERSUS PLACEBO PLUS MELPHALAN AND PREDNISONE IN SUBJECTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA WHO ARE 65 YEARS OF AGE OR OLDER

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00405756
• Other study ID #: CC-5013-MM-015
• Secondary ID: 2006-001865-41
• Status: Active, not recruiting
• Phase: Phase 3
• First received: November 29, 2006
• Last updated: October 26, 2015
• Start date: January 2007
• Est. completion date: December 2015

Study information

• Verified date: October 2015
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods AdministrationAustria: Agency for Health and Food SafetyBelarus: Ministry of HealthBelgium: Federal Agency for Medicinal Products and Health ProductsCzech Republic: State Institute for Drug ControlDenmark: Danish Medicines AgencyFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesGeorgia: Ministry of HealthGreece: National Organization of MedicinesIreland: Irish Medicines BoardIsrael: Israeli Health Ministry Pharmaceutical AdministrationItaly: The Italian Medicines AgencyNetherlands: Dutch Health Care InspectoratePoland: The Central Register of Clinical TrialsRussia: Ministry of Health of the Russian FederationSpain: Spanish Agency of MedicinesSweden: Medical Products AgencySwitzerland: SwissmedicTurkey: Ministry of HealthUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUkraine: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether lenalidomide is safe and effective in the treatment of patients with newly diagnosed Multiple Myeloma who are 65 years of age or older.

Description:

The three phases for the study as originally defined and as represented in the results of 11 May 2010 are:

Double-blind Treatment Phase: Induction Melphalan/prednisone and lenalidomide 10 mg (MPR) (2 treatment arms), or melphalan/prednisone and placebo (MPp) (1 treatment arm) for up to 9 cycles. If disease progression, subjects have the option to enter into the Open-Label Extension Phase. There is also an option to enter into the Follow-Up Phase. If the disease has not progressed, subject can continue blinded therapy into Maintenance.

Double-blind Treatment Phase: Maintenance One MPR treatment arm (MPR+R) will continue taking lenalidomide 10 mg in Maintenance. The other MPR treatment arm (MPR+p) will take placebo in Maintenance. The MPp treatment arm will take placebo in Maintenance (MPp+p). If disease progression, subjects have the option to enter the Open-Label Extension Phase to obtain treatment with lenalidomide, or to enter into the Follow-up Phase.

Open-label Extension Phase:

Treatment consists of oral lenalidomide (up to 25 mg) with or without dexamethasone until disease progression or treatment is discontinued for any reason until all study subjects are followed for at least 5 years from the date of randomization or have died. Subjects who discontinue from the Open-Label Extension Phase prior to completing a total of 5 years in the study will enter the Follow-up Phase.

Follow-up Phase:

Subjects are followed for overall survival and subsequent anti-myeloma treatment regimens until all subjects in this study are followed for at least 5 years from randomization or have died.

The pre-planned interim analysis for the Independent Data Monitoring Committee (IDMC) showed that the difference in progression-free survival (PFS) between treatment arms MPR+R and MPp+p (the defined primary comparative analysis for this study) surpassed the pre-specified O'Brien-Fleming boundary for superiority. The IDMC recommended the release of this information to the sponsor and also recommended that all patient and physician study participants receive information concerning the full findings of the MM-015 interim analysis. Therefore, due to these recommendations from the IDMC, treatment-arm codes were sent to the clinical trial centers to unblind the treatment arms of their study subjects once the amended protocol was reviewed and approved by the respective country Health Authorities and Ethics Committees. Subject participation in the MM-015 study continued after unblinding to obtain long-term data for all study endpoints, including overall survival.

When the study was unblinded, subjects still on protocol therapy had completed the Double-Blind Induction, and were on monotherapy in Double-Blind Maintenance. Subjects in arm MPR+R continued their monotherapy on lenalidomide. Subjects in arms MPR+p and MPp+p discontinued their placebo monotherapy and went into an observation period in which no antimyeloma therapy was taken. If disease progressed for any subject, the investigator had the option of entering the subject in Open Label Extension Phase to receive lenalidomide therapy (up to 25 mg daily) or the Follow-up Phase. All subjects were to be followed for at least 5 years from the start of the study.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 459
• Est. completion date: December 2015
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 65 Years and older

Eligibility

Inclusion Criteria

1. Must understand and voluntarily sign an informed consent form

2. Age greater than or equal to 65 years at the time of signing the informed consent

3. Newly diagnosed with symptomatic multiple myeloma as defined by the 3 criteria below:

MM diagnostic criteria (all of next 3 required)

1. Monoclonal plasma cells in the bone marrow greater than or equal to 10% and/or presence of a biopsy-proven plasmacytoma

2. Monoclonal protein present in the serum and/or urine

3. Myeloma-related organ dysfunction (at least one of the following) [C] Calcium elevation in the blood (serum calcium >10.5mg/dl or upper limit of normal) [R] Renal insufficiency (serum creatinine >2mg/dl) [A] Anemia (hemoglobin <10g/dl or 2g < normal) [B] Lytic bone lesions or osteoporosis AND have measurable disease as defined by the following; IgG multiple myeloma: Serum monoclonal paraprotein (M-protein) level greater than or equal to 1.0 g/dL or urine M-protein level greater than or equal to 200 mg/24 hours IgA multiple myeloma: Serum M-protein level greater than or equal to 0.5 g/dL or urine M-protein level greater than or equal to 200 mg/24 hours IgD multiple myeloma: Serum M-protein level greater than or equal to 0.05 g/dL or urine M-protein level greater than or equal to 200 mg/24 hours Light chain multiple myeloma: Serum M-protein level greater than or equal to 1.0 g/dL or urine M-protein level greater than or equal to 200 mg/24 hours IgM multiple myeloma (IgM M-protein plus lytic bone disease documented by skeletal survey plain films): Serum M-protein level greater than or equal to 1.0g/dL or urine M-protein level greater than or equal to 200mg/24hours

4. Karnofsky performance status greater than or equal to 60%.

5. Able to adhere to the study visit schedule and other protocol requirements.

6. Women of Childbearing potential (WCBP) must:

a. Have a negative medically supervised pregnancy test prior to the start of study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after end of study therapy. This applies even if the subject practices and continues sexual abstinence.

b Either commit to continued abstinence from heterosexual intercourse (which must be reviewed on a monthly basis) or agree to use, and be able to comply with, effective contraception without interruption, 28 days prior to starting study drug, during the study therapy (including dose interruptions), and for 28 days after discontinuation of study therapy.

7. Males Subjects must:

1. Agree to use a condom during sexual contact with a WCBP, even if they have had a vasectomy, throughout study drug therapy, during any dose interruption and after the cessation of study therapy.

2. Agree to not donate semen during study drug therapy and for a period after end of study drug therapy.

8. All subjects must

1. Have an understanding that the study drug could have potential teratogenic risk.

2. Agree to abstain from donating blood while taking study drug therapy and following discontinuation of study drug therapy.

3. Agree not to share study medication with another person.

4. All patients must be counseled about pregnancy precautions and risks of fetal exposure.

Female Subjects:

Females of childbearing potential (FCBP) with regular cycles must agree to have pregnancy tests weekly for the first 28 days of study participation and then every 28 days while on study, at study discontinuation, and at day 28 following discontinuation from the study. If menstrual cycles are irregular, the pregnancy testing must occur weekly for the first 28 days and then every 14 days while on study, at study discontinuation, and at days 14 and 28 following discontinuation from the study.

In addition to the required pregnancy testing, the Investigator must confirm with FCBP that she is continuing to use two reliable methods of birth control at each visit. Counseling about pregnancy precautions and the potential risks of fetal exposure must be conducted at a minimum of every 28 days. During counseling, subjects must be reminded to not share study drug and to not donate blood.

Pregnancy testing and counseling must be performed if a subject misses her period or if her pregnancy test or her menstrual bleeding is abnormal. Study drug treatment must be discontinued during this evaluation.

Females must agree to abstain from breastfeeding during study participation and for at least 28 days after the discontinuation from the study.

Male Subjects:

Counseling about the requirement for latex condom use during sexual contact with females of childbearing potential and the potential risks of fetal exposure must be conducted at a minimum of every 28 days. During counseling, subjects must be reminded to not share study drug and to not donate blood, sperm, or semen.

If pregnancy or a positive pregnancy test does occur in a study subject or the partner of a study subject during study participation, study drug must be immediately discontinued.

Exclusion Criteria

1. Previous treatment with antimyeloma therapy (does not include radiotherapy, bisphosphonates, or a single short course of steroid [i.e., less than or equal to the equivalent of dexamethasone 40 mg/day for 4 days; such a short course of steroid treatment must not have been given within 28 days [4 weeks] of randomization]).

2. Any serious medical condition, including the presence of laboratory abnormalities, which places the subject at an unacceptable risk if he or she participates in this study or confounds experimental the ability to interpret data from the study.

3. Pregnant or lactating females.

4. Radiotherapy within 14 days (2 weeks) of randomization.

5. Plasmapheresis within 28 days (4 weeks) of randomization.

6. Any of the following laboratory abnormalities:

Absolute neutrophil count (ANC) < 1,500 cells/mL (1.5*10^9/L) Platelet count < 75,000 cells/uL (75*10^9/L) for subjects in whom < 50% of bone marrow nucleated cells are plasma cells; but platelet count <30,000/uL for subjects in whom >= 50% of bone marrow nucleated cells are plasma cells Haemoglobin < 8.0 g/dL (80 g/L) Serum creatinine > 2.5 mg/dL (221 µmol/L) Serum aspartate aminotransferase (SGOT/AST) or alanine aminotransferase (SGPT/ALT) > 3.0 times upper limit of normal (ULN)

7. Prior history of malignancies, other than multiple myeloma, unless the subject has been free of the disease for greater than or equal to 3 years.

Exceptions include the following:

Basal cell carcinoma of the skin Squamous cell carcinoma of the skin Carcinoma in situ of the cervix Carcinoma in situ of the breast Incidental histologic finding of prostate cancer (TNM Classification of Malignant Tumours (TNM) stage of T1a or T1b)

8. Neuropathy of >= grade 2 severity.

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Newly Diagnosed Multiple Myeloma

Intervention

Drug:
• Lenalidomide: Double-blind Induction
Double-blind Induction: the starting lenalidomide oral dosing regimen was 10 mg once daily on Days 1 through 21 of each 28 day cycle for up to 9 cycles. Dose was reduced if needed due to dose-limiting toxicity.
• Melphalan
Double-blind Induction: the starting melphalan oral dosing regimen in all 3 treatment arms was 0.18 mg/kg daily on Days 1 through 4 of each 28-day cycle for up to 9 cycles. Dose was reduced if needed due to dose-limiting toxicity.
• Prednisone
Double-blind induction: the starting prednisone oral dosing regimen in all 3 treatment arms was 2 mg/kg daily on Days 1 through 4 of each 28-day cycle for up to 9 cycles. Dose was reduced if needed due to dose-limiting toxicity.
• Aspirin
Double-blind induction: low-dose aspirin 75 mg to 100 mg daily for all treatment arms. Double-blind maintenance: at the investigator's discretion
• Placebo
Double-blind induction: participants in treatment arm MPp+p received placebo once daily on Days 1 through 21 of each 28-day cycle for up to 9 cycles. Double-blind maintenance: participants in treatment arms MPR+p and MPp+p received placebo once daily on Days 1 through 21 of each 28-day cycle from cycle 10 to disease progression.
• Lenalidomide: Double-blind Maintenance
Single-agent oral lenalidomide 10 mg once daily on Days 1 through 21 of each 28-day cycle from cycle 10 to disease progression.
• Lenalidomide: Open-label
Any study participant who had progressive disease had the option of open-label lenalidomide up to 25 mg daily on Days 1 through 21 of each 28-day cycle.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital Institute of Medical and Veterinary Science	Adelaide	South Australia
Australia	Royal Prince Alfred Hospital	Camperdown
Australia	Peter MacCallum Cancer Centre Divsion of Haematology/Medical Oncology	East Melbourne
Australia	Frankston Hospital	Frankston
Australia	The Alfred Hospital	Melbourne
Australia	Sir Charles Gairdner Hospital	Nedlands
Australia	Hematology/Oncology Clinics of Australia, Level 5, Mater Medical Centre	South Brisbane	Queensland
Australia	Princess Alexandra Hospital	Woolloongabba
Austria	University Hospital Innsbruck	Innsbruck
Austria	University Hospital of Salzburg St Johanns Spital	Salzburg
Austria	Medical University of Vienna	Vienna
Austria	Medical University of Vienna	Vienna
Austria	Wilhelminenspital	Vienna
Belarus	Republican Scientific and Practical Centre of Radiation Medicine and Human Ecology	Gomel
Belarus	City Clinical Hospital # 9	Minsk
Belgium	AZ St-Jan Brugge Oostende AV	Brugge
Belgium	AZ-VUB	Brussels
Belgium	UZ Gasthuisberg	Leuven
Belgium	Centre Hospitalier Universitaire de Liege	Liege
Czech Republic	Fakultni nemocnice Brno	Brno
Czech Republic	Fakultni nemocnice Hradec Kralove	Hradec Kralove
Czech Republic	Fakultní Nemocnice Olomouc	Olomouc
Czech Republic	Vseobecna Fakultni Nemocnice v Praze	Prague
Denmark	Hæmatologisk afd. B Aalborg Sygehus Syd	Aalborg
Denmark	Medicinsk afd. Vejle Sygehus	Vejle
France	CHU	Caen
France	CH - Hôpital Dupuytren	Limoges Cedex 1
France	CHU Montpellier- Hopital Lapeyronie	Montpellier Cedex 5
France	Assistance Publique - Hôpitaux de Paris (AP-HP)	Paris
France	CHU Purpan	Toulouse cedex 9
Georgia	Institute of Hematology and Transfusiology	Tbilisi
Georgia	Ltd M.Zodelava Hematology Centre	Tbilisi
Germany	Medizinische Klinik und Poliklinik II der Charite Campus Mitte	Berlin
Germany	Universitätsklinikum Carl Gustav Carus an der TU Dresden	Dresden
Germany	Universitätsklinikum Freiburg Medizinische Klinik und Poliklinik	Freiburg
Germany	Ernst-Moritz-Arndt-Universität Greifswald	Greifswald
Germany	Universitaetsklinikum Heidelberg Medizinische Klinik und Poliklinik V	Heidelberg
Germany	Medizinische Klinik und Poliklinik II	Leipzig
Germany	Poliklinik A	Münster
Germany	Medizinische Klinik - Abteilung II	Tübingen
Germany	Medizinische Universitätsklinik	Ulm
Germany	Medizinische Klinik und Poliklinik II des Universitätsklinikums Würzburg	Würzburg
Greece	Alexandra General Hospital of Athens	Athens
Greece	G. GENNIMATAS General Hospital of Athens Department of Hematolgosy	Athens
Greece	General Air Force Hospital	Athens
Ireland	Hope Directorate Haematology Oncology Service St. James Hospital	Dublin
Ireland	Midlands Regional	Tullamore / Co Offally
Israel	Rambam Medical Center	Haifa
Israel	Hadassah University Hospital	Jerusalem
Israel	Hematology Institute, Hemato-Oncology Division,Davidoff Cancer Center, Rabin MC Beilinson Hospital	Petch Tikva
Israel	The Chaim Sheba Medical Center	Tel Hashomer
Italy	Policlinico S. Orsola	Bologna
Italy	A.O.U. San Martino	Genova
Italy	Dipartmento Oncologico Struttura Complessa di ematlologiaA.O. Ospedale Niguarda Ca Granda	Milano
Italy	Policlinico San Matteo Universita Di Pavia	Pavia 2
Italy	Azienda Policlinico Umberto I, Università "La Sapienza" di Roma	Rome
Italy	Divisione Di Ematologia Ospedale Cattedra di Ematologia	Rome
Italy	Dipartimento di Onco-Ematologia	San Giovanni Rotondo (FG)
Italy	Azienda Sanitaria Ospedaliera Molinette S. Giovanni Battista	Turin
Netherlands	VU Medical Center	Amsterdam
Netherlands	Erasmus Medical Center	Rotterdam
Netherlands	Erasmus Medisch Centrum	Rotterdam
Netherlands	Universitair Medisch Centrum Utrecht	Utrecht
Poland	Klinika Hematologii Samodzielny Publiczny Szpital Kliniczny Akademii	Bialystok
Poland	Institute of Internal Diseases University of Medicine	Gdansk
Poland	Oddzial Kliniczny Kliniki Hematologii	Krakow
Poland	Uniwersytet Medyczny w Lodzi	Lodz
Poland	University School of Medicine	Lublin
Poland	Akademia Medyczna w Warszawie Samodzielny Publiczny Centralny Szpital Kliniczny	Warsaw
Russian Federation	Burdenko Central Military Clinical Hospital	Moscow
Russian Federation	Institution of Russian Academy of Medical Sciences Russian Oncological Research Centre n.a. N. N. Bl	Moscow
Russian Federation	Moscow Regional Research Institute n.a. Vladimirsky	Moscow
Russian Federation	Novosibirsk State Regional Clinical Hospital	Novosibirsk
Russian Federation	Medical Radiological Research Center RAMS	Obninsk
Russian Federation	Samara Regional Clinical Hospital	Samara
Russian Federation	St. Petersburg Research Institute of Hematology and Blood Transfusion	St. Petersburg
Spain	Hospital Clinic	Barcelona
Spain	Hospital Universitaro Puerta del MarServicio de Hematologia	Cadiz
Spain	Hospital Universitario de la Princessa	Madrid
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	Hospital Virgen del RocíoServicio de Hematologia	Sevilla
Sweden	Medicinkliniken	Boras
Sweden	Medicinska kliniken	Malmö
Switzerland	UniversitätsSpital ZürichKlinik für Onkologie	Zurich
Turkey	Ankara University	Ankara
Turkey	Marmara School of Medicine	Istanbul
Turkey	Ege University Medical School	Izmir
Ukraine	Cherkassy Regional Oncology Center	Cherkassy
Ukraine	Dnepropetrovsk City Clinical Hospital #4	Dnepropetrovsk
Ukraine	Institute of Urgent and Recovery Surgery	Donetsk
Ukraine	Institute of Hematology and Transfusiology of the UAMS Department of blood diseases	Kiev
Ukraine	Institute of Blood Pathology and Transfusion Medicine of the AMS of Ukraine	Lviv 79044
Ukraine	Zhitomir Regional Clinical Hospital	Zhitomir
United Kingdom	Monklands Hospital	Aidrie
United Kingdom	St James's University Hospital	Leeds
United Kingdom	Kings College Hospital	London
United Kingdom	University College London Hospitals Cancer Clinical Trials Unitist FloorCentral wing	London
United Kingdom	Christie NHS Trust Hospital	Manchester

Sponsors (1)

Lead Sponsor	Collaborator
Celgene Corporation

Countries where clinical trial is conducted

Australia,  Austria,  Belarus,  Belgium,  Czech Republic,  Denmark,  France,  Georgia,  Germany,  Greece,  Ireland,  Israel,  Italy,  Netherlands,  Poland,  Russian Federation,  Spain,  Sweden,  Switzerland,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Kaplan Meier Estimates of Progression-free Survival (PFS) Based on the Response Assessment by the Central Adjudication Committee (CAC)	Data as of 11 May 2010 cutoff. PFS was calculated as the time from randomization to the earlier of the first documentation of progressive disease (PD) as determined by the CAC, or death on study due to any cause. PD was based on the European Group for Blood and Marrow Transplantation/International Bone Marrow Transplant Registry/Autologous Bone Marrow Transplant Registry [EBMT/IBMTR/ABMTR] criteria.; PD criteria includes increasing monoclonal paraprotein levels, bone marrow findings, worsening lytic bone disease, progressively enlarging extramedullary plasmacytomas, or hypercalcemia.	up to 165 weeks	No
Secondary	Kaplan Meier Estimates of Progression-free Survival (PFS) From Start of Maintenance Therapy Period Based on the Response Assessment by the Central Adjudication Committee (CAC)	Data as of 11 May 2010 cutoff. PFS calculated from the start of the Maintenance period to the earlier of the first documentation of progressive disease (PD) as determined by the CAC, or death on study due to any cause.; PD was based on the European Group for Blood and Marrow Transplantation/International Bone Marrow Transplant Registry/Autologous Bone Marrow Transplant Registry [EBMT/IBMTR/ABMTR] criteria.; PD criteria includes increasing monoclonal paraprotein levels, bone marrow findings, worsening lytic bone disease, progressively enlarging extramedullary plasmacytomas, or hypercalcemia.	Approximately week 37 (start of cycle 10) to week 165	No
Secondary	Kaplan Meier Estimates of Overall Survival (OS)	Data as of 11 May 2010 cutoff. Overall survival (OS) was defined as the time between randomization and death. Participants who died, regardless of the cause of death, were considered to have had an event. Participants who were lost to follow-up prior to the end of the trial, or who were withdrawn from the trial, were censored at the time of last contact. Participants who were still being treated were censored at the last available date available, or clinical cut-off date, if it was earlier.	up to 177 weeks	No
Secondary	Kaplan Meier Estimates of Time to Progression (TTP) Based on the Response Assessment by the Central Adjudication Committee (CAC)	Data as of 11 May 2010 cutoff. TTP was the time between randomization and disease progression as determined by the CAC. PD was based on the European Group for Blood and Marrow Transplantation/International Bone Marrow Transplant Registry/Autologous Bone Marrow Transplant Registry [EBMT/IBMTR/ABMTR] criteria.; PD criteria includes increasing monoclonal paraprotein levels, bone marrow findings, worsening lytic bone disease, progressively enlarging extramedullary plasmacytomas, or hypercalcemia.	up to 165 weeks	No
Secondary	Number of Participants in Disease Response Categories Representing Their Best Response During the Double-blind Treatment Period	Data as of 11 May 2010 cutoff. Best response was determined by the Central Assessment Committee (CAC) based on the European Group for Blood and Marrow Transplantation (EBMT) criteria: Complete Response (CR)-absence of serum and urine monoclonal paraprotein for 6 weeks, plus no increase in size or number of bone lesions, plus other factors); Partial Response (PR)-not all CR criteria, plus >=50% reduction in serum monoclonal paraprotein plus others; Stable Disease (SD)- not PR or PD; Progressive Disease (PD)- reappearance of monoclonal paraprotein, bone lesions, other; Not Evaluable (NE).	Up to 165 weeks	No
Secondary	Time to First Response	Data as of 11 May 2010 cutoff. Time to first response was defined as the time from start of treatment until first response as assessed by the Central Assessment Committee (CMC) based on European Group for Blood and Marrow Transplantation (EBMT) criteria.	Up to 66 weeks	No
Secondary	Kaplan Meier Estimates for Duration of Response as Determined by the Central Adjudication Committee (CAC)	Data as of 11 May 2010 cutoff. Duration of myeloma response was defined as the time from the initial response date to the earlier of progressive disease (PD) as determined by the CAC or death on study. PD was based on the European Group for Blood and Marrow Transplantation/International Bone Marrow Transplant Registry/Autologous Bone Marrow Transplant Registry [EBMT/IBMTR/ABMTR] criteria.; PD criteria includes increasing monoclonal paraprotein levels, bone marrow findings, worsening lytic bone disease, progressively enlarging extramedullary plasmacytomas, or hypercalcemia.	Up to 149 weeks	No
Secondary	Kaplan Meier Estimates for Time to Next Antimyeloma Therapy	Data as of 11 May 2010 cutoff. Time to the next antimyeloma therapy was defined as time from randomization to the start of another non-protocol antimyeloma therapy. Participants who do not receive another anti-myeloma therapy were censored at the last assessment or follow-up visit known to have received no new therapy.	Up to 168 weeks	No
Secondary	Summary of Participants With Treatment-Emergent Adverse Events (TEAE) During the Double-Blind Treatment Period	Data as of 11 May 2010 cutoff. Participant counts in different categories of TEAEs during the double-blind treatment period. A TEAE is as any AE occurring or worsening on or after the first treatment of any study drug, and within 30 days after the last dose of the last study drug. Severity grades according to Common Terminology Criteria for Adverse Events v3.0 (CTCAE) on a 1-5 scale: Grade 1= Mild AE, Grade 2= Moderate AE, Grade 3= Severe AE, Grade 4= Life-threatening or disabling AE, Grade 5=Death related to AE. Dose reduction includes reduction with or without interruption.	Up to 169 weeks (Double-blind therapy period plus 4 weeks)	Yes
Secondary	Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Quality of Life Scale	Data as of 11 May 2010 cutoff. EORTC QLC-C30 is a 30-item questionnaire to assess the quality of life in cancer patients. EORTC QLQ-C30 includes functional scales (physical, role, cognitive, emotional, social), global health status, symptom scales (fatigue, pain, nausea/vomiting), and other (dyspnoea, appetite loss, insomnia, constipation/diarrhea, financial difficulties). Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); two used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score = better quality of life.	Baseline (Day 0), Months 4, 7, 10, 13, 16	No
Secondary	Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Physical Functioning Scale	Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score=better level of physical functioning.	Baseline (Day 0), Months 4, 7, 10, 13, 16	No
Secondary	Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Role Functioning Scale	Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score=better level of role functioning.	Baseline (Day 0), Months 4, 7, 10, 13, 16	No
Secondary	Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Emotional Functioning Scale	Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score = better level of emotional functioning.	Baseline (Day 0), Months 4, 7, 10, 13, 16	No
Secondary	Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Congitive Functioning Scale	Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score = better level of cognitive functioning.	Baseline (Day 0), Months 4, 7, 10, 13, 16	No
Secondary	Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Social Functioning Scale	Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score = better level of social functioning.	Baseline (Day 0), Months 4, 7, 10, 13, 16	No
Secondary	Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Fatigue Scale	Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the fatigue scale = higher level of symptomatology/problems.	Baseline (Day 0), Months 4, 7, 10, 13, 16	No
Secondary	Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Nausea and Vomiting Scale	Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the nausea/vomiting scale = higher level of symptomatology/problems.	Baseline (Day 0), Months 4, 7, 10, 13, 16	No
Secondary	Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Pain Scale	Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the pain scale = higher level of symptomatology/problems.	Baseline (Day 0), Months 4, 7, 10, 13, 16	No
Secondary	Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Dyspnoea Scale	Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the dyspnoea scale = higher level of symptomatology/problems.	Baseline (Day 0), Months 4, 7, 10, 13, 16	No
Secondary	Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Insomnia Scale	Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the insomnia scale = higher level of symptomatology/problems.	Baseline (Day 0), Months 4, 7, 10, 13, 16	No
Secondary	Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Appetite Loss Scale	Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the appetite loss scale = higher level of symptomatology/problems.	Baseline (Day 0), Months 4, 7, 10, 13, 16	No
Secondary	Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Constipation Scale	Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the constipation scale = higher level of symptomatology/problems.	Baseline (Day 0), Months 4, 7, 10, 13, 16	No
Secondary	Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Diarrhoea Scale	Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the diarrhea scale = higher level of symptomatology/problems.	Baseline (Day 0), Months 4, 7, 10, 13, 16	No
Secondary	Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Financial Difficulties Scale	Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a problem scale like the financial problems scale = higher level of financial problems.	Baseline (Day 0), Months 4, 7, 10, 13, 16	No
Secondary	Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms Scale	Data as of 11 May 2010 cutoff. EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. EORTC QLQ-MY20 includes four scales: disease symptoms, treatment side-effects, future perspective, and body image. Questions used 4-point scale (1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to 0-100 scale; higher score for the disease symptoms scale = higher level of symptomatology.	Baseline (Day 0), Months 4, 7, 10, 13, 16	No
Secondary	Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) In Side Effects of Treatment Scale	Data as of 11 May 2010 cutoff. EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. Questions used 4-point scale (1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to 0-100 scale; higher score for the side effects scale = higher level of symptomatology.	Baseline (Day 0), Months 4, 7, 10, 13, 16	No
Secondary	Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) In Future Perspective Scale	Data as of 11 May 2010 cutoff. EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. Questions used 4-point scale (1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to 0-100 scale. For the future perspective scale, higher score = better perspective of the future.	Baseline (Day 0), Months 4, 7, 10, 13, 16	No
Secondary	Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) In Body Image Scale	Data as of 11 May 2010 cutoff. EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. Questions used 4-point scale (1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to 0-100 scale. For the body image scale, higher scores = better body image.	Baseline (Day 0), Months 4, 7, 10, 13, 16	No