A Study of Combination of Daratumumab and Velcade (Bortezomib) Melphalan-Prednisone (DVMP) Compared to Velcade Melphalan-Prednisone (VMP) in Participants With Previously Untreated Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Velcade; Melphalan; Prednisone; Daratumumab IV; Dexamethasone; Daratumumab SC
Intervention description: Participants will receive velcade 1.3 mg/m^2, as subcutaneous injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at Weeks 1, 2, 4 and 5 in Cycles 2 to 9.; Participants will receive melphalan 9 mg/m^2, orally, once daily on Days 1 to 4 of each cycle up to Cycle 9.; Participants will receive prednisone 60 mg/m^2, orally, once daily, on Days 1 to 4 of each cycle up to Cycle 9.; Participants will receive daratumumab 16 mg/kg as intravenous infusion, once weekly, for 6 weeks in Cycle 1 and then once every 3 weeks, in Cycle 2 to 9 and thereafter, once every 4 weeks until documented progression, unacceptable toxicity, or until the end of study .; Participants administered with dexamethasone 20 mg IV or PO is given 1 hour or less prior to daratumumab administration as pre medication and prednisone substitute.; Daratumumab SC will be administered by SC injection at a fixed dose of 1800 mg once every 4 weeks until documented progression, unacceptable toxicity, or until the end of study. Following amendment 7, participants can switch from daratumumab IV to daratumumab SC.
Intervention MeSH terms: Dexamethasone; Prednisone; Melphalan; Bortezomib; Daratumumab; Antibodies, Monoclonal
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 706.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Multiple Myeloma; Bortezomib; Velcade; Melphalan; Prednisone; Daratumumab

Summary:

      The purpose of this study is to determine if the addition of daratumumab to velcade
      (bortezomib) melphalan-prednisone (VMP) will prolong progression-free survival (PFS) compared
      with VMP alone in participants with previously untreated multiple myeloma who are ineligible
      for high dose chemotherapy and autologous stem cell transplant (ASCT).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participant must have documented multiple myeloma satisfying the calcium elevation,
             renal insufficiency, anemia, and bone abnormalities (CRAB) diagnostic criteria,
             monoclonal plasma cells in the bone marrow greater than or equal to 10 percent (%) or
             presence of a biopsy proven plasmacytoma, and measurable secretory disease, as
             assessed by the central laboratory, and defined in protocol

          -  Participants who are newly diagnosed and not considered candidate for high-dose
             chemotherapy with stem cell transplantation (SCT) due to: being age >=65 years, or in
             participants <65 years: presence of important comorbid conditions likely to have a
             negative impact on tolerability of high dose chemotherapy with stem cell
             transplantation

          -  Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status
             score of 0, 1, or 2

          -  Meet the clinical laboratory criteria as specified in the protocol

          -  A woman of childbearing potential must have a negative serum pregnancy test at
             screening within 14 days prior to randomization

          -  Women of childbearing potential must commit to either abstain continuously from
             heterosexual sexual intercourse or to use 2 methods of reliable birth control
             simultaneously. This includes one highly effective form of contraception (tubal
             ligation, intrauterine device, hormonal [birth control pills, injections, hormonal
             patches, vaginal rings or implants] or partner's vasectomy) and one additional
             effective contraceptive method (male latex or synthetic condom, diaphragm, or cervical
             cap). Contraception must begin prior to dosing. Reliable contraception is indicated
             even where there has been a history of infertility, unless due to hysterectomy or
             bilateral oophorectomy

        Exclusion Criteria:

          -  Participant has a diagnosis of primary amyloidosis, monoclonal gammopathy of
             undetermined significance, or smoldering multiple myeloma

          -  Participant has a diagnosis of Waldenstrom's disease, or other conditions in which IgM
             M-protein is present in the absence of a clonal plasma cell infiltration with lytic
             bone lesions

          -  Participant has prior or current systemic therapy or SCT for multiple myeloma, with
             the exception of an emergency use of a short course (equivalent of dexamethasone 40
             mg/day for 4 days) of corticosteroids before treatment

          -  Participant has peripheral neuropathy or neuropathic pain Grade 2 or higher, as
             defined by the national cancer institute common terminology criteria for adverse
             events (NCI CTCAE) Version 4

          -  Participant has a history of malignancy (other than multiple myeloma) within 3 years
             before the date of randomization (exceptions are squamous and basal cell carcinomas of
             the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the
             investigator, with concurrence with the sponsor's medical monitor, is considered cured
             with minimal risk of recurrence within 3 years)

          -  Participant has had radiation therapy within 14 days of randomization

          -  Participant has had plasmapheresis within 28 days of randomization

          -  Participant has known chronic obstructive pulmonary disease (COPD) (defined as a
             forced expiratory volume in 1 second [FEV1] <50% of predicted normal), known moderate
             or severe persistent asthma within the last 2 years or currently has uncontrolled
             asthma of any classification (controlled intermittent asthma or controlled mild
             persistent asthma is allowed)

          -  Participants with known or suspected COPD must have a FEV1 test during screening

          -  Participant is known to be seropositive for human immunodeficiency virus (HIV), known
             to have hepatitis B surface antigen positivity, or history of to have a history of
             hepatitis C

          -  Participant has any concurrent medical or psychiatric condition or disease (example
             active systemic infection, uncontrolled diabetes, acute diffuse infiltrative pulmonary
             disease) that is likely to interfere with the study procedures or results, or that in
             the opinion of the investigator, would constitute a hazard for participating in this
             study