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

• 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 ]

• 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.

The purpose of the study is to determine whether the addition of Elotuzumab to Bortezomib/ Dexamethasone will increase the time before myeloma worsens [progression free survival (PFS)].

• 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®
  • Dexamethasone
  • 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®
  • Dexamethasone
  • 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®
  • Dexamethasone
  • 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®
  • Dexamethasone
  • 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

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