Addition of Daratumumab to Combination of Bortezomib and Dexamethasone in Participants With Relapsed or Refractory Multiple Myeloma

Phase 3 Study Comparing Daratumumab, Bortezomib and Dexamethasone (DVd) vs Bortezomib and Dexamethasone (Vd) in Subjects With Relapsed or Refractory Multiple Myeloma

The purpose of this study is to assess the effects of administration of daratumumab when combined with VELCADE (bortezomib) and dexamethasone compared with bortezomib and dexamethasone alone, for participants with relapsed or refractory multiple myeloma.

This is an open-label (physicians and participants know the identity of the assigned treatment), randomized (the study medication is assigned by chance), multicenter, active-controlled study comparing daratumumab, VELCADE, and dexamethasone (DVd) with VELCADE and dexamethasone (Vd) in participants with relapsed or refractory multiple myeloma. Approximately 480 participants will be randomly assigned in a 1:1 ratio to receive either DVd or Vd. Randomization will be stratified by International Staging System (ISS), number of prior treatment programs (1 vs. 2 or 3 vs. >3), and prior VELCADE treatment ("no" vs. "yes"). Within each stratum, participants will be randomized to one of the treatment groups.The study will consist of a Screening Phase, a Treatment Phase, and a Follow-up Phase. Participants will be treated until disease progression, unacceptable toxicity, or other reasons to discontinue the study.

Inclusion Criteria:

• Must have had documented multiple myeloma
• Must have received at least 1 prior line of therapy for multiple myeloma
• Must have had documented evidence of progressive disease as defined based on Investigator's determination of response of International Myeloma Working Group (IMWG) criteria on or after their last regimen
• Must have an Eastern Cooperative Oncology Group Performance Status score of 0, 1, or 2
• Must have achieved a response (partial response [PR] or better based on investigator's determination of response by the IMWG criteria) to at least 1 prior regimen in the past

Exclusion Criteria:

• Has received daratumumab or other anti-CD38 therapies previously
• Is refractory to VELCADE or another PI, like ixazomib and carfilzomib (had progression of disease while receiving VELCADE therapy or within 60 days of ending VELCADE therapy or another PI therapy, like ixazomib and carfilzomib
• Is intolerant to VELCADE (ie, discontinued due to any adverse event while on VELCADE treatment)
• Has received anti-myeloma treatment within 2 weeks or 5 pharmacokinetic half-lives of the treatment, whichever is longer, before the date of randomization. The only exception is emergency use of a short course of corticosteroids (equivalent of dexamethasone 40 milligram per day [mg/day] for a maximum of 4 days) before treatment. A list of anti-myeloma treatments with the corresponding pharmacokinetic half-lives is provided in the Site Investigational Product Procedures Manual (IPPM).
• Has a history of malignancy (other than multiple myeloma) within 3 years before the date of randomization
• Has any concurrent medical condition or disease (eg, active systemic infection) that is likely to interfere with study procedures