Velcade,Thalidomide, and Dexamethasone Versus Velcade and Dexamethasone Versus Velcade, Melphalan, and Prednisone

Multiple Myeloma Clinical Trial

— UPFRONT  

Official title:

Randomized Phase 3b Study of Three Treatment Regimens in Subjects With Previously Untreated Multiple Myeloma Who Are Not Considered Candidates for High-Dose Chemotherapy and Autologous Stem Cell Transplantation: VELCADE, Thalidomide, and Dexamethasone Versus VELCADE and Dexamethasone Versus VELCADE, Melphalan, and Prednisone

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00507416
• Other study ID #: C05009
• Status: Completed
• Phase: Phase 3
• First received: July 25, 2007
• Last updated: March 28, 2014
• Start date: June 2007
• Est. completion date: March 2013

Study information

• Verified date: March 2014
• Source: Millennium Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This is a randomized, open label, multicenter clinical trial to compare the efficacy and safety of Velcade (bortezomib) and dexamethasone versus Velcade, thalidomide, and dexamethasone versus Velcade, melphalan, and prednisone in patients with previously untreated multiple myeloma not considered candidates for high-dose chemotherapy and autologous stem cell transplantation.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 502
• Est. completion date: March 2013
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male or female 18 years of age or older

• Not a candidate for high-dose chemotherapy and stem cell transplantation (HDT/SCT) due to age, presence of important comorbid condition(s) likely to have a negative impact on tolerability of HDT-SCT, or subject preference.

• A Karnofsky Performance Status score of =50%

• Symptomatic multiple myeloma or asymptomatic multiple myeloma with related organ or tissue damage.

• Asymptomatic multiple myeloma-related organ or tissue damage can include presence of an asymptomatic lytic bone lesion or plasmacytoma, the presence of anemia (hemoglobin <10 g/dL), renal function impairment (serum creatinine > upper limit of normal [ULN]) or hypercalcemia (serum calcium >ULN).

• Must have measurable disease requiring systemic therapy. Measurable disease is defined by at least 1 of the following criteria:

• Quantifiable serum M-protein value (>1 g/dL of immunoglobulin (Ig)G or IgM M-protein, >0.5g/dL of IgA M-protein, >0.5 g/dL of IgD M-protein)

• Urine light-chain excretion =200 mg/24 hours

• Voluntary written informed consent must be given before performance of any study related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care.

Exclusion Criteria:

• Diagnosis of smoldering multiple myeloma or monoclonal gammopathy of undetermined significance (MGUS). Smoldering multiple myeloma is defined as asymptomatic multiple myeloma with absence of lytic bone lesions. MGUS is defined by presence of serum monoclonal protein <3 g/dL; absence of lytic bone lesions, anemia, hypercalcemia, and renal insufficiency related to the monoclonal protein; and (if determined) proportion of plasma cells in the bone marrow of 10% or less.

• Diagnosis of Waldenström's disease or other conditions in which immunoglobulin M (IgM) M-protein is present in the absence of a clonal plasma cell infiltration or lytic bone lesions.

• Previously or currently treated with any systemic therapy for multiple myeloma. Prior treatment of hypercalcemia or spinal cord compression with corticosteroids or radiation therapy, respectively, does not disqualify the subject (the dose of corticosteroids should not exceed the equivalent of 160 mg of dexamethasone in 2-week period).

• Radiation therapy within 2 weeks before randomization. Enrollment of patients who require concurrent radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 2 weeks have elapsed since the last date of therapy.

• Major surgery within 30 days before randomization (Kyphoplasty is not considered major surgery)

• History of allergy to any of the study medications, their analogues, or excipients in the various formulations

• =Grade 2 peripheral neuropathy on clinical examination within 21 days before enrollment.

• Any of the following clinical laboratory values within 21 days prior to enrollment:

• Absolute neutrophil count (ANC) <1000 cells/mm^3

• Platelets <100,000 × 10^9/L, or <70 × 10^9/L if thrombocytopenia is considered by the investigator to be due to myeloma infiltration of bone marrow

• Aspartate aminotransferase [serum glutamic oxaloacetic transaminase] (AST [SGOT]) or alanine aminotransferase [serum glutamic-pyruvic transaminase] (ALT [SGPT]) >2× the upper limit of normal (ULN)

• Serum creatinine >2 mg/dL (>176.8 µmol/L); if the rise in creatinine is related to myeloma and there has been demonstrated a response to hydration, the subject may be enrolled.

• Myocardial infarction within 6 months prior to enrollment or New York Hospital Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or significant conduction system abnormalities in the opinion of the investigator. Prior to study entry, any abnormality on electrocardiogram at screening must be determined and documented by the investigator as not medically relevant.

• Any condition, including laboratory abnormalities, that in the opinion of the Investigator places the patient at unacceptable risk if he/she were to participate in the study. This includes but is not limited to serious medical conditions or psychiatric illness likely to interfere with participation in this clinical study.

• Prior malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, in situ breast cancer, in situ prostate cancer, or other cancer for which the patient has been disease-free for at least 3 years.

• Female who is pregnant or breastfeeding. Female participants of childbearing potential must have a negative pregnancy test with a sensitivity of at least 50 mIU/mL during Screening.

• Use of any investigational drugs within 30 days before randomization.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Bortezomib
Bortezomib bolus intravenous (IV) injection
• Dexamethasone
Dexamethasone for oral administration
• Melphalan
Melphalan for oral administration
• Prednisone
Prednisone for oral administration
• Thalidomide
Thalidomide for oral administration

Locations

Country	Name	City	State
Puerto Rico	Hospital Auxillo Mutuo, Auxilio Mutuo Cancer Center	San Juan
United States	Texas Cancer Center	Abilene	Texas
United States	Stratton VA Medical Center IRB	Albany	New York
United States	Christus St. Francis Cabrini Cancer Center	Alexandria	Louisiana
United States	McFarland Clinic, P.C.	Ames	Iowa
United States	Pacific Cancer Medical Centre	Anaheim	California
United States	Annapolis Oncology Center	Annapolis	Maryland
United States	Texas Oncology, P.A.	Arlington	Texas
United States	Cancer Care & Hematology Specialists of Chicagoland	Arlington Heights	Illinois
United States	Cancer Care of WNC	Asheville	North Carolina
United States	Medical Oncology Associates of Augusta	Augusta	Georgia
United States	Southwest Regional Cancer Center	Austin	Texas
United States	Texas Oncology, PA	Austin	Texas
United States	Auerbach Hematology Oncology Associates	Baltimore	Maryland
United States	Greater Baltimore Medical Center	Baltimore	Maryland
United States	Maryland Hematology Oncology Association	Baltimore	Maryland
United States	St. Agnes Health Care	Baltimore	Maryland
United States	Hematology-Oncology Clinic	Baton Rouge	Louisiana
United States	Texas Oncology, PA	Beaumont	Texas
United States	Texas Oncology, P.A.	Bedford	Texas
United States	Center for Cancer and Blood Disorders	Bethesda	Maryland
United States	Onc-Hem of Lehigh Valley, PC	Bethlehem	Pennsylvania
United States	Tower Cancer Research Foundation	Beverly Hills	California
United States	Birmingham Hematology Oncology Assciates, LLC	Birmingham	Alabama
United States	St. Alexius Clinical Research Services	Bismark	North Dakota
United States	The Center for Hematology-Oncology	Boca Raton	Florida
United States	St. Lukes Mountain States Tumor Institute	Boise	Idaho
United States	Boston Medical Center	Boston	Massachusetts
United States	Eastchester Center for Cancer Care	Bronx	New York
United States	Pasco Hernando Oncology	Brooksville	Florida
United States	Buffalo Institute for Medical Research, Inc.	Buffalo	New York
United States	Erie County Medical Center	Buffalo	New York
United States	Alamance Regional Medical Center	Burlington	North Carolina
United States	The University of Vermont	Burlington	Vermont
United States	Gabrail Cancer Center	Canton	Ohio
United States	Desert Oasis Cancer Center	Casa Grande	Arizona
United States	MUSC Hollings Cancer Center	Charleston	South Carolina
United States	Chattanooga Oncology Hematology Associates	Chattanooga	Tennessee
United States	Cancer Specialists of Tidewater	Chesapeake	Virginia
United States	St. Louis Cancer Center	Chesterfield	Missouri
United States	Hematology Oncology Associates of Illinois	Chicago	Illinois
United States	Hematology Oncology Associates of Illinois	Chicago	Illinois
United States	John H. Stroger, Jr. Hospital of Cook County	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	Oncology Hematology Care, Inc.	Cincinnati	Ohio
United States	Oncology Partners Network	Cincinnati	Ohio
United States	University Hospitals of Cleveland	Cleveland	Ohio
United States	Oncology-Hematology Associates, P.A.	Clinton	Maryland
United States	The Family Cancer Center, PLLC	Collierville	Tennessee
United States	Maryland Oncology Hematology, PA	Columbia	Maryland
United States	Hematology Oncology Consultants Inc.	Columbus	Ohio
United States	The Cancer Center of Cookeville Regional Medical Center	Cookeville	Tennessee
United States	Northwest Oncology & Hematology Associates	Coral Springs	Florida
United States	Compassionate Cancer Care Medical Group	Corona	California
United States	Coastal Bend Cancer Center	Corpus Christi	Texas
United States	South Texas Institute of Cancer and Blood Disorders	Corpus Christi	Texas
United States	Heartland Hematology-Oncology Associates, Inc.	Council Bluffs	Iowa
United States	Dallas Oncology Consultants	Dallas	Texas
United States	Texas Oncology	Dallas	Texas
United States	Texas Oncology PA	Dallas	Texas
United States	Texas Oncology, PA / Methodist Charlton Cancer Center	Dallas	Texas
United States	Commonwealth Cancer Center	Danville	Kentucky
United States	Dayton Clinical Oncology Program	Dayton	Ohio
United States	Texas Cancer Center	Denton	Texas
United States	Rocky Mountain Cancer Center	Denver	Colorado
United States	Henry Ford Health System	Detroit	Michigan
United States	St. Luke's Hospital	Duluth	Minnesota
United States	Hematology & Oncology Associates of NEPA	Dunmore	Pennsylvania
United States	Veterans Affairs New Jersey Healthcare System	East Orange	New Jersey
United States	Puget Sound Cancer Center - Edmonds	Edmonds	Washington
United States	El Paso Cancer Treatment Center	El Paso	Texas
United States	Elmhurst Memorial Hospital	Elmhurst	Illinois
United States	Drs. Forte, Schleider, Attas and Condemi, PA	Englewood	New Jersey
United States	Willamette Valley Cancer Center	Eugene	Oregon
United States	Deaconess Clinic Incorporated	Evansville	Indiana
United States	Providence Everett Medical Center	Everett	Washington
United States	Fairfax/Northern Virginia Hematology/Oncology	Fairfax	Virginia
United States	Blood and Cancer Clinic	Fayetteville	North Carolina
United States	Florida Cancer Specialists	Fort Myers	Florida
United States	Texas Cancer Center	Fort Worth	Texas
United States	Compassionate Cancer Care Medical Group, Inc.	Fountain Valley	California
United States	Robert A. Moss, MD, FACP, Inc.	Fountain Valley	California
United States	Cancer Care Associates	Fresno	California
United States	Texas Oncology, PA	Garland	Texas
United States	Gaston Hematology & Oncology	Gastonia	North Carolina
United States	The Jones Clinic	Germantown	Tennessee
United States	Glendale Memorial Hospital & Health Center	Glendale	California
United States	Goshen Medical Associates	Goshen	New York
United States	Cancer & Hematology Centers of Western Michigan	Grand Rapids	Michigan
United States	Lee C. Drinkard, MD	Grapevine	Texas
United States	Great Falls Clinic, LLP	Great Falls	Montana
United States	California Cancer Care	Greenbrae	California
United States	Cancer Center of the Carolinas	Greenville	South Carolina
United States	Oncology Hematology Associates of North Illinois Ltd.	Gurnee	Illinois
United States	Kentucky Cancer Clinic	Hazard	Kentucky
United States	Las Vegas Cancer Center	Henderson	Nevada
United States	Carolina Oncology Specialist, PA	Hickory	North Carolina
United States	Emerywood Hematology/Oncology	High Point	North Carolina
United States	Beaver Medical Group	Highland	California
United States	Horizon Institute for Clinical Research	Hollywood	Florida
United States	Heritage Physician Group Oncology	Hot Springs	Arkansas
United States	Houston Cancer Institute	Houston	Texas
United States	Medicus Alliance Clinical Research Organization, LLC	Houston	Texas
United States	Huntington Medical Group	Huntington Station	New York
United States	Snake River Oncology of Eastern Idaho, PLLC.	Idaho Falls	Idaho
United States	Central Indiana Cancer Centers	Indianapolis	Indiana
United States	Investigative Clinical Research of Indiana, LLC	Indianapolis	Indiana
United States	Baptist Cancer Institute	Jacksonville	Florida
United States	University of Florida- Jacksonville	Jacksonville	Florida
United States	Capital Region Medical Center/Cancer Center	Jefferson City	Missouri
United States	Joliet Oncology-Hematology Associates, Ltd.	Joliet	Illinois
United States	Midwest Center for Hematology / Oncology	Joliet	Illinois
United States	Kalamazoo Hematology and Oncology	Kalamazoo	Michigan
United States	Heartland Hematology-Oncology Associates, Inc.	Kansas City	Missouri
United States	Kansas City Veterans Administration Medical Center	Kansas City	Missouri
United States	Dayton Oncology & Hematology	Kettering	Ohio
United States	Medical Oncology Associates	Kingston	Pennsylvania
United States	East Tennessee Oncology/Hematology	Knoxville	Tennessee
United States	University of Tennesee Medical Center	Knoxville	Tennessee
United States	Gundersen Clinic, Ltd.	La Crosse	Wisconsin
United States	Clarian Arnett Cancer Center	Lafayette	Indiana
United States	Edward A. Wagner, MD	Laguna Beach	California
United States	Cancer Care of North Florida	Lake City	Florida
United States	North Shore-Long Island Jewish Health System	Lake Success	New York
United States	Lakeland Regional Cancer Center	Lakeland	Florida
United States	Hematology Oncology Associates of Ohio & Michigan, PC	Lambertville	Michigan
United States	Regional Hematology Oncology Associates	Langhorne	Pennsylvania
United States	Breslin Cancer Center / Great Lakes Cancer Institute	Lansing	Michigan
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Cancer & Blood Disease Center	Lecanto	Florida
United States	Lake Vista Cancer Center	Lewisville	Texas
United States	Hematology Oncology Services of Arkansas	Little Rock	Arkansas
United States	St. Barnabas Medical Center	Livingston	New Jersey
United States	Longview Cancer Center	Longview	Texas
United States	Lynchburg Hematology Oncology Clinic, Inc.	Lynchburg	Virginia
United States	Central Georgia Cancer Care	Macon	Georgia
United States	Northwest Georgia Oncology Centers, P.C.	Marietta	Georgia
United States	Texas Cancer Center of Mesquite	Mesquite	Texas
United States	Texas Oncology, P.A.	Midland	Texas
United States	Metro MN CCOP	Minneapolis	Minnesota
United States	Clinical Trials and Research Associates, Inc.	Montebello	California
United States	Low Country Hematology & Oncology	Mt. Pleasant	South Carolina
United States	Medical Consultants, PC	Muncie	Indiana
United States	Hematology Oncology Consultants, Inc.	Naperville	Illinois
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Cancer Care Center	New Albany	Indiana
United States	Arena Oncology Associates	New Hyde Park	New York
United States	Florida Cancer Institute	New Port Richey	Florida
United States	Pasco Hernando Oncology	New Port Richey	Florida
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	New York Presbyterian Hospital-Cornell Campus	New York	New York
United States	Christiana Care Health Services	Newark	Delaware
United States	Newark Beth Israel Hospital	Newark	New Jersey
United States	Peninsula Cancer Institute Riverside Cancer Center	Newport News	Virginia
United States	Cancer Care and Hematology Specialists of Chicagoland	Niles	Illinois
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	Mid-Illinois Hem & Onc	Normal	Illinois
United States	Innovative Medical Research of South Florida Inc.	North Miami Beach	Florida
United States	Great Plains Regional Medical Center	North Platte	Nebraska
United States	Ocala Oncology Center	Ocala	Florida
United States	Cancer Centers of Florida, P.A.	Ocoee	Florida
United States	Texas Oncology - Odessa	Odessa	Texas
United States	Northern Utah Associates	Ogden	Utah
United States	Cancer Care Associates	Oklahoma City	Oklahoma
United States	Creighton Cancer Center	Omaha	Nebraska
United States	Medical Oncology Care Associates	Orange	California
United States	MD Anderson Cancer Center Orlando	Orlando	Florida
United States	Kansas City Cancer Centers - Southwest	Overland Park	Kansas
United States	Ventura County Hematology Oncology Specialists	Oxnard	California
United States	Western Kentucky Hematology and Oncology Group	Paducah	Kentucky
United States	Paris Regional Cancer Center	Paris	Texas
United States	Greater Philadelphia Cancer and Hematology Specialists, PC	Philadelphia	Pennsylvania
United States	UPMC Cancer Pavillioin	Pittsburgh	Pennsylvania
United States	Hematology Oncology Associates of the Treasure Coast, PA	Port St. Lucie	Florida
United States	Southwest Cancer Care	Poway	California
United States	Roger Williams Medical Center	Providence	Rhode Island
United States	Quincy Medical Group	Quincy	Illinois
United States	Raleigh Hematology Oncology / Associates, P.C.	Raleigh	North Carolina
United States	Desert Cancer Care, Incorporated	Rancho Mirage	California
United States	Virginia Cancer Institute	Richmond	Virginia
United States	Compassionate Cancer Care Medical Group, Inc.	Riverside	California
United States	Hubert H. Humphrey Cancer Center	Robbinsdale	Minnesota
United States	Interlakes Foundation, Inc.	Rochester	New York
United States	Sutter Cancer Center	Sacramento	California
United States	Oncology and Hematology Associates of Southwest Virginia, Inc.	Salem	Virginia
United States	Utah Cancer Specialists	Salt Lake City	Utah
United States	Cancer Care Center of South Texas	San Antonio	Texas
United States	Cancer Care Network of South Texas	San Antonio	Texas
United States	CTRC Institute for Drug Development	San Antonio	Texas
United States	New Mexico Cancer Care Associates	Santa Fe	New Mexico
United States	Summit Cancer Care	Savannah	Georgia
United States	Guthrie Research Institute	Sayre	Pennsylvania
United States	Scranton Hematology Oncology	Scranton	Pennsylvania
United States	Puget Sound Cancer Center, Inc	Seattle	Washington
United States	Northern Arizona Hematology & Oncology Associates - AOA	Sedona	Arizona
United States	Texas Cancer Center - Sherman	Sherman	Texas
United States	Siouxland Hematology/Oncology Assoc., LLP	Sioux City	Iowa
United States	Avera Research Institute	Sioux Falls	South Dakota
United States	Somerset Hematology Oncology Associates	Somerville	New Jersey
United States	Cancer Research & Prevention Center	Soquel	California
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Providence Cancer Center	Southfield	Michigan
United States	Cancer Center of Central Connecticut	Southington	Connecticut
United States	Sparta Cancer Center	Sparta	New Jersey
United States	Cancer Care Northwest, US Oncology	Spokane	Washington
United States	Oncology Care Associates, P.L.L.C.	St. Joseph	Michigan
United States	St. Joseph Oncology	St. Joseph	Missouri
United States	Gulfcoast Oncology Associates	St. Petersburg	Florida
United States	Richmond University Medical Center	Staten Island	New York
United States	Stockton Hematology/Oncology	Stockton	California
United States	Santee Hematology/Oncology	Sumter	South Carolina
United States	SUNY Upstate Medical University	Syracuse	New York
United States	Northwest Medical Specialties, PLLC	Tacoma	Washington
United States	Hope Center	Terre Haute	Indiana
United States	Toledo Community Hospital Oncology Program	Toledo	Ohio
United States	Arizona Oncology Associates	Tucson	Arizona
United States	Oklahoma Oncology and Hematology	Tulsa	Oklahoma
United States	Blood and Cancer Center of East Texas	Tyler	Texas
United States	Texas Oncology, PA	Tyler	Texas
United States	Tyler Hematology/Oncology, PA	Tyler	Texas
United States	New York Medical College	Valhalla	New York
United States	Texas Oncology	Waco	Texas
United States	Wenatchee Valley Medical Center	Wenatchee	Washington
United States	Alyce & Elmore Kraemer Cancer Center	West Bend	Wisconsin
United States	S. Florida Oncology/ Hematology	West Palm Beach	Florida
United States	Trivalley Oncology Hematology	Westlake Village	California
United States	Carroll County Cancer Center	Westminster	Maryland
United States	White River Junction VAMC	White River Junction	Vermont
United States	Cancer Center of Kansas	Wichita	Kansas
United States	Hanover Medical Specialists, P.A.	Wilmington	North Carolina
United States	Masoom Kandahari, MD, PC	Woodbridge	Virginia
United States	Osteopathic Medical Hematology & Oncology	Woodhaven	Michigan
United States	Trilogy Cancer Center	Wooster	Ohio
United States	Fallon Clinic at Worcester Medical Center	Worcester	Massachusetts
United States	Yakima Valley Memorial Hospital / North Star Lodge	Yakima	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Millennium Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS)	PFS is defined as the time from randomization to disease progression or death, whichever occurs first. Participants who did not progress and were still alive at the cut-off date were censored at the date of last contact. Response was assessed by the Investigator using the International Myeloma Working Group (IMWG) uniform response criteria.; Progressive disease requires 1 of the following: Increase of = 25% from nadir in: Serum M-component (absolute increase = 0.5 g/dl); Urine M-component (absolute increase = 200 mg/24 hours); In patients without measurable serum and urine M-protein levels the difference between involved and uninvolved free light chain (FLC) levels (absolute increase > 100 mg/dl); 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 disease progression. Median follow-up time was 43 months.	No
Secondary	Percentage of Participants With an Overall Response	Overall response defined as a best overall response of complete response (CR), very good partial response (VGPR) or partial response (PR), assessed by the Investigator using the IMWG uniform response criteria.; CR: Negative immunofixation on the serum and urine, 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 plus urine M-protein level <100 mg per 24 hours (h).; PR requires 1 of the following: =50% reduction of serum M-protein and 24-h urinary M-protein by = 90% or to <200 mg/24 h, or; If M-protein not measurable, a =50% decrease in the difference between involved and uninvolved FLC levels, or; If FLC not measurable, a = 50% reduction in plasma cells, provided baseline bone marrow plasma cell percentage was =30%.; If present at baseline, a =50% reduction in the size of soft tissue plasmacytomas is also required.	Response assessed every other cycle for up to 13 cycles (49 weeks).	No
Secondary	Percentage of Participants With a Complete Response	Participants with a best overall response of complete response, defined as negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas, and <5% plasma cells in bone marrow. Response was assessed by the Investigator using the IMWG uniform response criteria.	Response assessed every other cycle, for up to 13 cycles (49 weeks).	No
Secondary	Percentage of Participants With a Complete Response or a Very Good Partial Response	Complete response is defined by negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas, and <5% plasma cells in bone marrow.; Very good partial response is defined by serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level <100 mg per 24 hours.; Response was assessed by the Investigator using the IMWG uniform response criteria.	Response assessed every other cycle for up to 13 cycles (49 weeks).	No
Secondary	Duration of Response	Duration of response is defined in participants with an overall response as the time between first documentation of response and disease progression. Responders without disease progression were censored at the last clinical assessment of response.	From first documented response until disease progression. Median follow-up time was 43 months.	No
Secondary	Overall Survival	Overall survival is defined as the time between randomization and death. Participants still alive at the cutoff date or lost to follow-up were censored at the date of last contact.	From randomization until death. Median follow-up time was 43 months.	No
Secondary	Time to Alternative Therapy	Time to alternative therapy is defined as the time between randomization and alternative therapy. Participants who did not receive alternative therapy were censored at the time of last contact.	From randomization until alternative therapy. Median follow-up time was 43 months.	No
Secondary	Change From Baseline in EORTC QLQ-C30 - Global Health Status	The European Organisation 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, where higher scores indicate better Global Health Status/QOL. Negative changes from baseline indicate deterioration in QOL or functioning and positive changes indicate improvement.	Baseline and Day 1 of Cycles 3, 5, 7, 9, 11 and 13	No