Study of Bortezomib and Dexamethasone With or Without Elotuzumab to Treat Relapsed or Refractory Multiple Myeloma
A Phase 2, Randomized Study of Bortezomib/Dexamethasone With or Without Elotuzumab in Subjects With Relapsed/Refractory Multiple Myeloma
Study Overview
Status
Status
Conditions
Conditions
Intervention / Treatment
Intervention / Treatment
Study Type
Study Type
Enrollment (Actual)
Enrollment
Phase
Phase
- Phase 2
Contacts and Locations
Study Locations
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Nova Scotia
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Halifax, Nova Scotia, Canada, B3H 2Y9
- Local Institution
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Grenoble Cedex 9, France, 38043
- Local Institution
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Le Mans, France, 72037
- Local Institution
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Lille Cedex, France, 59037
- Local Institution
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Nantes, France, 44093
- Local Institution
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Paris 12, France, 75012
- Local Institution
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Toulouse, France, 31059
- Local Institution
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Vandoeuvre Les Nancy, France, 54500
- Local Institution
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Ancona, Italy, 60126
- Local Institution
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Bari, Italy, 70124
- Local Institution
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Bologna, Italy, 40138
- Local Institution
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Brescia, Italy, 25123
- Local Institution
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Firenze, Italy, 50134
- Local Institution
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Genova, Italy, 16132
- Local Institution
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Lecce, Italy, 73100
- Local Institution
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Meldola (fc), Italy, 47014
- Local Institution
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Modena, Italy, 41124
- Local Institution
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Pescara, Italy, 65124
- Local Institution
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Ravenna, Italy, 48100
- Local Institution
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Rimini, Italy, 47900
- Local Institution
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Roma, Italy, 00168
- Local Institution
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Roma, Italy, 161
- Local Institution
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Rome, Italy, 00144
- Local Institution
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Torino, Italy, 10126
- Local Institution
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Parma
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Milano, Parma, Italy, 20132
- Local Institution
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Roma, Parma, Italy, 00144
- Local Institution
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Barcelona, Spain, 08003
- Local Institution
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Madrid, Spain, 28006
- Local Institution
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Murcia, Spain, 30008
- Local Institution
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Salamanca, Spain, 37007
- Local Institution
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Santiago Compostela, Spain, 15706
- Local Institution
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Toledo, Spain, 45004
- Local Institution
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Valencia, Spain, 46026
- Local Institution
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Valencia, Spain, 46010
- Local Institution
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Zaragoza, Spain, 50009
- Local Institution
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California
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Corona, California, United States, 92879
- Compassionate Cancer Res Grp
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Corona, California, United States, 92879
- Local Institution
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Long Beach, California, United States, 90806
- Local Institution
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Los Angeles, California, United States, 90033
- USC Norris Comprehensive Cancer Center
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Los Angeles, California, United States, 90095
- UCLA Department of Medicine
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Orange, California, United States, 92868
- Medical Oncology Care Associates
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San Diego, California, United States, 92123
- Sharp Clinical Oncology Research
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Vallejo, California, United States, 94589
- Kaiser Permanente Medical Center
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Vallejo, California, United States, 94589
- Local Institution
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Florida
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Jacksonville, Florida, United States, 32256
- Cancer Specialists of North FL
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Miami Beach, Florida, United States, 33140
- Mount Sinai Comprehensive Cancer Center
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West Palm Beach, Florida, United States, 33401
- Palm Beach Cancer Institute
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Hawaii
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Honolulu, Hawaii, United States, 96819
- Kaiser Permanente-Moanalua Medical Center
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Illinois
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Chicago, Illinois, United States, 60637
- University of Chicago Medical Center
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Decatur, Illinois, United States, 62526
- Local Institution
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Park Ridge, Illinois, United States, 60068
- Oncology Specialists, S.C.
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Urbana, Illinois, United States, 61801
- Local Institution
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Indiana
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Indianapolis, Indiana, United States, 46260
- Investigative Clinical Research of Indiana, LLC
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Kentucky
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Hazard, Kentucky, United States, 41701
- Local Institution
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Lexington, Kentucky, United States, 40536
- University of Kentucky Markey Cancer Center
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Pikeville, Kentucky, United States, 41501
- Pikeville Medical Center Leonard Lawson Cancer Center
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Louisiana
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Lafayette, Louisiana, United States, 70503
- Cancer Center of Acadiana
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Shreveport, Louisiana, United States, 71101
- Local Institution
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Maryland
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Baltimore, Maryland, United States, 21204
- Local Institution
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Massachusetts
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Boston, Massachusetts, United States, 02215
- Dana-Farber Cancer Institute
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Worcester, Massachusetts, United States, 01608
- Local Institution
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Michigan
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Detroit, Michigan, United States, 48202
- Henry Ford Health System
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Missouri
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Saint Louis, Missouri, United States, 63110
- Washington University School of Medicine
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Springfield, Missouri, United States, 65807
- Mercy Medical Research Institute
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Nevada
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Las Vegas, Nevada, United States, 89106
- Southern Nevada Cancer Research Foundation
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North Carolina
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Cary, North Carolina, United States, 27518
- Waverly Hematology Oncology
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Pennsylvania
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Baltimore, Pennsylvania, United States, 21229
- St. Agnes Hospital
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Bethlehem, Pennsylvania, United States, 18015
- Cancer Care Associates
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Hershey, Pennsylvania, United States, 17033
- Penn State Hershey Cancer Institute
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Hershey, Pennsylvania, United States, 17033
- Penn State Hershey Cancer Inst
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Pittsburgh, Pennsylvania, United States, 15224
- The Western Pennsylvania Hospital
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South Carolina
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Charleston, South Carolina, United States, 29425
- Medical University of South Carolina
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Greenville, South Carolina, United States, 29615
- Local Institution
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Texas
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Dallas, Texas, United States, 75246
- Charles A. Sammons Cancer Center
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Houston, Texas, United States, 77090
- Northwest Cancer Center
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Virginia
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Fairfax, Virginia, United States, 22031
- Local Institution
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Washington
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Seattle, Washington, United States, 98108
- Local Institution
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Participation Criteria
Eligibility Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
For additional information, please contact the BMS oncology clinical trial information service at 855-216-0126 or email MyCancerStudyConnect@emergingmed.com. Please visit www.BMSStudyConnect.com for more information on clinical trial participation.
Inclusion Criteria:
- Documented progression from most recent line of therapy
- Measurable disease
1 to 3 prior lines of therapy
Subjects may be proteasome inhibitor naive or have received prior proteasome inhibitor therapy provided all the following criteria are met:
- The subject did not discontinue any proteasome inhibitor due to intolerance or grade ≥ 3 toxicity
- The subject is not refractory to any proteasome inhibitor, defined as progression during treatment or within 60 days after the last dose
- The subject previously achieved a partial response (PR) or better to previous proteasome inhibitor (PI)
Exclusion Criteria:
- Monoclonal gammopathy of undetermined significance (MGUS), smoldering myeloma, or Waldenstrom's macroglobulinemia
- Active plasma cell leukemia
- Known Human immunodeficiency virus (HIV) infection or active hepatitis A, B, or C
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Number of Arms
Arms and Interventions
Participant Group / ArmParticipant Group / Arm |
Intervention / TreatmentIntervention / Treatment |
|---|---|
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Experimental: Arm A: Elotuzumab + Bortezomib + Dexamethasone
On days of Elotuzumab infusion: Dexamethasone (8mg IV + 8mg Oral) will be administered other days Dexamethasone 20 mg Oral will be administered
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Solution; Intravenous (IV); 10 mg/kg; (Cycles 1 & 2: Days 1, 8 & 15; Cycles 3-8: Days 1 & 11; Cycle 9+: Days 1 & 15); Until subject meets criteria for discontinuation of study drug
Other Names:
Solution; IV; 1.3 mg/m2; (Cycles 1 - 8: Days 1, 4, 8, 11; Cycles 9+: Days 1, 8, 15); Until subject meets criteria for discontinuation of study drug
Other Names:
Tablets; Oral; 20 mg; (Cycles 1& 2: once daily on Days 2, 4, 5, 8, 9, 11; Cycles 3-8: once daily on Days 2, 4, 5, 9, 12; Cycles 9+: once daily on Days 2, 8, 9, 16); Until subject meets criteria for discontinuation of study drug
Other Names:
Tablets; Oral; 8 mg; (Cycles 1& 2: Days 1, 8, 15; Cycles 3-8: Days 1 &11; Cycles 9+; Days 1 & 15); Until subject meets criteria for discontinuation of study drug
Other Names:
Solution; IV; 8 mg; (Cycles 1& 2: Days 1, 8, 15; Cycles 3-8: Days 1 &11; Cycles 9+; Days 1 & 15); Until subject meets criteria for discontinuation of study drug
Other Names:
Tablets; Oral; 20 mg; (Cycles 1-8 once daily on Days 1, 2, 4, 5, 8, 9, 11, 12; Cycles 9+ once daily on Days 1, 2, 8, 9, 15, 16); Until subject meets criteria for discontinuation of study drug
Other Names:
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Active Comparator: Arm B: Bortezomib + Dexamethasone
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Solution; IV; 1.3 mg/m2; (Cycles 1 - 8: Days 1, 4, 8, 11; Cycles 9+: Days 1, 8, 15); Until subject meets criteria for discontinuation of study drug
Other Names:
Tablets; Oral; 20 mg; (Cycles 1& 2: once daily on Days 2, 4, 5, 8, 9, 11; Cycles 3-8: once daily on Days 2, 4, 5, 9, 12; Cycles 9+: once daily on Days 2, 8, 9, 16); Until subject meets criteria for discontinuation of study drug
Other Names:
Tablets; Oral; 8 mg; (Cycles 1& 2: Days 1, 8, 15; Cycles 3-8: Days 1 &11; Cycles 9+; Days 1 & 15); Until subject meets criteria for discontinuation of study drug
Other Names:
Solution; IV; 8 mg; (Cycles 1& 2: Days 1, 8, 15; Cycles 3-8: Days 1 &11; Cycles 9+; Days 1 & 15); Until subject meets criteria for discontinuation of study drug
Other Names:
Tablets; Oral; 20 mg; (Cycles 1-8 once daily on Days 1, 2, 4, 5, 8, 9, 11, 12; Cycles 9+ once daily on Days 1, 2, 8, 9, 15, 16); Until subject meets criteria for discontinuation of study drug
Other Names:
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What is the study measuring?
Primary Outcome Measures
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Median Investigator-Assessed Progression-free Survival (PFS) Time (Months) From Randomization to Date of First Tumor Progression or Death Due to Any Cause - Randomized Participants
Time Frame: Randomization until 111 events (disease progression or death), up to May 2014, approximately 2 years
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PE was planned for after at least 103 events; it was analyzed after 111 events.
Response was assessed: Day 1 (± 7 days) of each cycle per modified International Myeloma Working Group (IMWG) criteria; assessed using adequate tumor assessment (ATA) (ie, serum and urine M-protein tests performed within 14 days of each other; imaging if baseline measurable extramedullary plasmacytoma existed).
Progression: Any of following: Increase of 25% from lowest response in 1 or more: serum and/or urine M-component; in those without measurable serum and urine M-protein levels, difference between involved and uninvolved free light chain (FLC) levels (absolute increase > 100 mg/L); Bone marrow plasma cell percentage (≥10%).
Definite new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing lesions or plasmacytomas.
Development of hypercalcemia attributed solely to the plasma cell proliferative disorder.
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Randomization until 111 events (disease progression or death), up to May 2014, approximately 2 years
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Number of Investigator-Assessed Progression-free Survival Events From Randomization to Date of First Tumor Progression or Death Due to Any Cause - All Randomized Participants
Time Frame: Randomization until 111 events, up to May 2014, approximately 2 years
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PE planned for after at least 103 events (progression/death); analyzed at 111 events.
Those who neither progressed nor died were censored on the date of last adequate tumor assessment (ATA), which requires both serum and urine M-protein tests.
If no post-baseline tumor assessments/no death, then censored on randomization day.
Response assessed: Day 1 (± 7 days) each cycle; 30 and 60 days post treatment.
Modified IMWG criteria used.
Progression: Any of following: Increase of 25% in serum and/or urine M-component; if no measurable serum, urine M-protein levels, then difference between involved and uninvolved free light chain (FLC) levels (absolute increase > 100 mg/L) ; Bone marrow plasma cell percentage (≥10%).
New bone lesions or soft tissue plasmacytomas or increase in size of existing lesions, plasmacytomas.
Development of hypercalcemia attributed solely to plasma cell proliferative disorder.
First dose occurs within 3 days of randomization.
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Randomization until 111 events, up to May 2014, approximately 2 years
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1 Year Progression-Free Survival Rate - Randomized Participants
Time Frame: Year 1 after last participant was randomized
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PFS rate=Percentage probability of participants experiencing no progression or death up to 1 year, estimated using the Kaplan-Meier method.
Response assessed by the investigator: Day 1 (± 7 days) of each cycle per modified IMWG criteria; assessed using ATA (ie, serum and urine M-protein tests performed within 14 days of each other; imaging done if baseline measurable extramedullary plasmacytoma existed).
Progression: Any of the following: Increase of 25% from lowest response in 1 or more: serum and/or urine M-component; in those without measurable serum and urine M-protein levels, difference between involved and uninvolved FLC levels (absolute increase > 100 mg/L) ; Bone marrow plasma cell percentage (≥10%).
Definite new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing lesions or plasmacytomas.
Development of hypercalcemia attributed solely to the plasma cell proliferative disorder.
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Year 1 after last participant was randomized
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Secondary Outcome Measures
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Median Progression-free Survival Time (Months) From Randomization to Date of First Tumor Progression or Death Due to Any Cause, in Randomized Participants With at Least One FcγRIIIa V Allele
Time Frame: Randomization until 111 events, up to May 2014, approximately 2 years
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PE was planned for after at least 103 events; it was analyzed after 111 events.
Response was assessed: Day 1 (± 7 days) of each cycle per modified IMWG criteria; assessed using adequate tumor assessment (ATA) (ie, serum and urine M-protein tests performed within 14 days of each other; imaging if baseline measurable extramedullary plasmacytoma existed).
Progression: Any of following: Increase of 25% from lowest response in 1 or more: serum and/or urine M-component; in those without measurable serum and urine M-protein levels, difference between involved and uninvolved FLC levels (absolute increase > 100 mg/L); Bone marrow plasma cell percentage (≥10%).
Definite new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing lesions or plasmacytomas.
Development of hypercalcemia attributed solely to the plasma cell proliferative disorder.
Randomized participants with at least 1 FcγRIIIa V allele were a sub-set of all randomized participants.
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Randomization until 111 events, up to May 2014, approximately 2 years
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Investigator-Assessed Objective Response Rate (ORR) - All Randomized Participants
Time Frame: Randomization until 111 events, up to May 2014, approximately 2 years
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ORR was calculated for participants with a best overall response (BOR) of partial response (PR) or better, including stringent complete response (sCR), complete response (CR), and very good partial response (VGPR).
BOR was determined by the investigator based on myeloma tumor assessments using IMWG criteria: CR=Negative immunofixation of serum and urine and disappearance of any soft tissue plasmacytomas, and < 5% plasma cells in bone marrow; sCR= CR + normal FLC ratio and absence of clonal cells in bone marrow; VGPR=Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein level + urine M-protein level < 100 mg per 24 hour; PR= ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥ 90% or to < 200 mg per 24 hour.
ORR= number of participants responding divided by total number of participants randomized, measured as a percentage.
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Randomization until 111 events, up to May 2014, approximately 2 years
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Investigator-Assessed Objective Response Rate in Randomized Participants With at Least One FcγRIIIa V Allele
Time Frame: Randomization until 111 events, up to May 2014, approximately 2 years
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ORR was calculated for participants with a BOR of PR or better, sCR, CR, and VGPR.
BOR was determined by the investigator based on myeloma tumor assessments using IMWG criteria: CR=Negative immunofixation of serum and urine and disappearance of any soft tissue plasmacytomas, and < 5% plasma cells in bone marrow; sCR= CR + normal FLC ratio and absence of clonal cells in bone marrow; VGPR=Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein level + urine M-protein level < 100 mg per 24 hour; PR= ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥ 90% or to < 200 mg per 24 hour.
ORR= number of participants responding divided by total number of participants randomized, measured as a percentage.
Randomized participants with at least 1 FcγRIIIa V allele were a sub-set of all randomized participants.
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Randomization until 111 events, up to May 2014, approximately 2 years
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Collaborators and Investigators
Sponsor
Sponsor
Collaborators
Collaborators
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Study Start
Primary Completion (Actual)
Primary Completion
Study Completion (Actual)
Study Completion
Study Registration Dates
First Submitted
First Submitted
First Submitted That Met QC Criteria
First Submitted That Met QC Criteria
First Posted (Estimate)
First Posted
Study Record Updates
Last Update Posted (Actual)
Last Update Posted
Last Update Submitted That Met QC Criteria
Last Update Submitted That Met QC Criteria
Last Verified
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Autonomic Agents
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Anti-Inflammatory Agents
- Antineoplastic Agents
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Protease Inhibitors
- Dexamethasone
- Dexamethasone acetate
- BB 1101
- Bortezomib
- Elotuzumab
Other Study ID Numbers
Other Study ID Numbers
- CA204-009
- 2011-002695-16 (EudraCT Number)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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