Study of Bortezomib and Dexamethasone With or Without Elotuzumab to Treat Relapsed or Refractory Multiple Myeloma
- Conditions
- Multiple Myeloma
- Interventions
- Registration Number
- NCT01478048
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
The purpose of the study is to determine whether the addition of Elotuzumab to Bortezomib/ Dexamethasone will prolong the time before myeloma worsens \[progression free survival (PFS)\].
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 185
-
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)
-
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A: Elotuzumab + Bortezomib + Dexamethasone Elotuzumab On days of Elotuzumab infusion: Dexamethasone (8mg IV + 8mg Oral) will be administered other days Dexamethasone 20 mg Oral will be administered Arm A: Elotuzumab + Bortezomib + Dexamethasone Bortezomib On days of Elotuzumab infusion: Dexamethasone (8mg IV + 8mg Oral) will be administered other days Dexamethasone 20 mg Oral will be administered Arm A: Elotuzumab + Bortezomib + Dexamethasone Dexamethasone On days of Elotuzumab infusion: Dexamethasone (8mg IV + 8mg Oral) will be administered other days Dexamethasone 20 mg Oral will be administered Arm B: Bortezomib + Dexamethasone Bortezomib - Arm B: Bortezomib + Dexamethasone Dexamethasone -
- Primary Outcome Measures
Name Time Method 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 Randomization until 111 events (disease progression or death), up to May 2014, approximately 2 years 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.
1 Year Progression-Free Survival Rate - Randomized Participants Year 1 after last participant was randomized 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.
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 Randomization until 111 events, up to May 2014, approximately 2 years 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.
- Secondary Outcome Measures
Name Time Method Investigator-Assessed Objective Response Rate (ORR) - All Randomized Participants Randomization until 111 events, up to May 2014, approximately 2 years 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.
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 Randomization until 111 events, up to May 2014, approximately 2 years 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.
Investigator-Assessed Objective Response Rate in Randomized Participants With at Least One FcγRIIIa V Allele Randomization until 111 events, up to May 2014, approximately 2 years 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.
Trial Locations
- Locations (31)
Cancer Center Of Acadiana
🇺🇸Lafayette, Louisiana, United States
Medical University Of South Carolina
🇺🇸Charleston, South Carolina, United States
Ucla Department Of Medicine
🇺🇸Los Angeles, California, United States
University Of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Local Institution
🇪🇸Zaragoza, Spain
Pikeville Medical Center Leonard Lawson Cancer Center
🇺🇸Pikeville, Kentucky, United States
Compassionate Cancer Res Grp
🇺🇸Corona, California, United States
Mercy Medical Research Institute
🇺🇸Springfield, Missouri, United States
Waverly Hematology Oncology
🇺🇸Cary, North Carolina, United States
St. Agnes Hospital
🇺🇸Baltimore, Pennsylvania, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
The Western Pennsylvania Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Cancer Care Associates
🇺🇸Bethlehem, Pennsylvania, United States
Washington University School Of Medicine
🇺🇸Saint Louis, Missouri, United States
Sharp Clinical Oncology Research
🇺🇸San Diego, California, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Southern Nevada Cancer Research Foundation
🇺🇸Las Vegas, Nevada, United States
Northwest Cancer Center
🇺🇸Houston, Texas, United States
USC Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Medical Oncology Care Associates
🇺🇸Orange, California, United States
Cancer Specialists of North FL
🇺🇸Jacksonville, Florida, United States
Mount Sinai Comprehensive Cancer Center
🇺🇸Miami Beach, Florida, United States
Kaiser Permanente-Moanalua Medical Center
🇺🇸Honolulu, Hawaii, United States
Palm Beach Cancer Institute
🇺🇸West Palm Beach, Florida, United States
Oncology Specialists, S.C.
🇺🇸Park Ridge, Illinois, United States
University Of Kentucky Markey Cancer Center
🇺🇸Lexington, Kentucky, United States
Investigative Clinical Research Of Indiana, Llc
🇺🇸Indianapolis, Indiana, United States
Kaiser Permanente Medical Center
🇺🇸Vallejo, California, United States
Penn State Hershey Cancer Institute
🇺🇸Hershey, Pennsylvania, United States
Penn State Hershey Cancer Inst
🇺🇸Hershey, Pennsylvania, United States
Charles A. Sammons Cancer Center
🇺🇸Dallas, Texas, United States