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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
AbbVie
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01478048
First received: November 2, 2011
Last updated: January 26, 2016
Last verified: January 2016

November 2, 2011
January 26, 2016
November 2011
May 2014   (final data collection date for primary outcome measure)
  • 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 ] [ Designated as safety issue: No ]
    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.
  • 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 ] [ Designated as safety issue: No ]
    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.
  • 1 Year Progression-Free Survival Rate - Randomized Participants [ Time Frame: Year 1 after last participant was randomized ] [ Designated as safety issue: No ]
    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.
  • Progression-free survival (PFS) - Time from randomization to date of first tumor progression or death due to any cause [ Time Frame: Every 21 +/-7 days (Cycles 1-8) relative to the first dose of study medication ] [ Designated as safety issue: No ]
  • Progression-free survival (PFS) - Time from randomization to date of first tumor progression or death due to any cause [ Time Frame: Every 28 +/- 7 days (Cycles 9+) relative to the first dose of study medication ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01478048 on ClinicalTrials.gov Archive Site
  • 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 ] [ Designated as safety issue: No ]
    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 (ORR) - All Randomized Participants [ Time Frame: Randomization until 111 events, up to May 2014, approximately 2 years ] [ Designated as safety issue: No ]
    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.
  • 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 ] [ Designated as safety issue: No ]
    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.
  • PFS hazard ration in the subgroup of subjects with at least one FcγRIIIa V allele [ Time Frame: Every 21 +/-7 days (Cycles 1-8) then every 28 +/- 7 days (Cycles 9+) relative to the first dose of study medication. ] [ Designated as safety issue: No ]
    Survival will be assessed every 12 weeks in the Follow Up Phase of the trial.
  • Difference in response rates between treatment arms in the overall population [ Time Frame: Every 21 +/-7 days (Cycles 1-8) then every 28 +/- 7 days (Cycles 9+) relative to the first dose of study medication. ] [ Designated as safety issue: No ]
    Survival will be assessed every 12 weeks in the Follow Up Phase of the trial.
  • Estimate the difference in response rates between arms in the subgroup of subjects with at least one FcγRIIIa V allele [ Time Frame: Every 21 +/-7 days (Cycles 1-8) then every 28 +/- 7 days (Cycles 9+) relative to the first dose of study medication. ] [ Designated as safety issue: No ]
    Survival will be assessed every 12 weeks in the Follow Up Phase of the trial.
Not Provided
Not Provided
 
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
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)].
Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Multiple Myeloma
  • Biological: Elotuzumab
    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 Name: BMS-901608
  • Drug: Bortezomib
    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 Name: Velcade®
  • Drug: Dexamethasone
    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:
    • Decadron®
    • Intensol®
    • Dexpak®
    • Taperpak®
  • Drug: Dexamethasone
    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:
    • Decadron®
    • Intensol®
    • Dexpak®
    • Taperpak®
  • Drug: Dexamethasone
    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:
    • Decadron®
    • Intensol®
    • Dexpak®
    • Taperpak®
  • Drug: Dexamethasone
    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:
    • Decadron®
    • Intensol®
    • Dexpak®
    • Taperpak®
  • 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
    Interventions:
    • Biological: Elotuzumab
    • Drug: Bortezomib
    • Drug: Dexamethasone
    • Drug: Dexamethasone
    • Drug: Dexamethasone
  • Active Comparator: Arm B: Bortezomib + Dexamethasone
    Interventions:
    • Drug: Bortezomib
    • Drug: Dexamethasone
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
185
April 2016
May 2014   (final data collection date for primary outcome measure)

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:

      1. The subject did not discontinue any proteasome inhibitor due to intolerance or grade ≥ 3 toxicity
      2. The subject is not refractory to any proteasome inhibitor, defined as progression during treatment or within 60 days after the last dose
      3. 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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada,   France,   Italy,   Spain
Puerto Rico
 
NCT01478048
CA204-009, 2011-002695-16
Yes
Not Provided
Not Provided
Bristol-Myers Squibb
Bristol-Myers Squibb
AbbVie
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
Bristol-Myers Squibb
January 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP