Study of Bortezomib and Dexamethasone With or Without Elotuzumab to Treat Relapsed or Refractory Multiple Myeloma

Study Overview
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Brief Summary
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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)].

Official Title
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A Phase 2, Randomized Study of Bortezomib/Dexamethasone With or Without Elotuzumab in Subjects With Relapsed/Refractory Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Biological: Elotuzumab
* Drug: Bortezomib
* Drug: Dexamethasone
* Drug: Dexamethasone
* Drug: Dexamethasone
* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: Elotuzumab + Bortezomib + Dexamethasone<br>On days of Elotuzumab infusion: Dexamethasone (8mg IV + 8mg Oral) will be administered other days Dexamethasone 20 mg Oral will be administered | Biological: Elotuzumab<br>* 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<br>* Other names: BMS-901608;Drug: Bortezomib<br>* 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<br>* Other names: Velcade®;Drug: Dexamethasone<br>* 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<br>* Other names: Taperpak®;Drug: Dexamethasone<br>* 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<br>* Other names: Taperpak®;Drug: Dexamethasone<br>* 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<br>* Other names: Taperpak®;|
| Active Comparator: Arm B: Bortezomib + Dexamethasone<br> | Drug: Bortezomib<br>* 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<br>* Other names: Velcade®;Drug: Dexamethasone<br>* 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<br>* Other names: Taperpak®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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. | Randomization until 111 events (disease progression or death), up to May 2014, approximately 2 years | 
| 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 | 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. | Randomization until 111 events, up to May 2014, approximately 2 years | 
| 1 Year Progression-Free Survival Rate - Randomized Participants | 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. | Year 1 after last participant was randomized | 

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 | 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. | Randomization until 111 events, up to May 2014, approximately 2 years | 
| Investigator-Assessed Objective Response Rate (ORR) - All Randomized Participants | 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. | Randomization until 111 events, up to May 2014, approximately 2 years | 
| Investigator-Assessed Objective Response Rate in Randomized Participants With at Least One FcγRIIIa V Allele | 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. | Randomization until 111 events, up to May 2014, approximately 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Relapsed/Refractory Multiple Myeloma