Study Comparing Daratumumab, Lenalidomide, Bortezomib, and Dexamethasone (D-RVd) Versus Lenalidomide, Bortezomib, and Dexamethasone (RVd) in Subjects With Newly Diagnosed Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Lenalidomide; Bortezomib; Dexamethasone; Daratumumab
Intervention description: Cycles 1 through 6: lenalidomide 25 (milligram) mg orally on Days 1 through 14 and each cycle is of 21-days followed by maintenance treatment with lenalidomide 10 mg on days 1-21 throughout each 28-day cycle on Cycles 7 through 9. Beginning at Cycle 10, the lenalidomide dose will be increased to 15 mg unless there is a tolerability concern.; Bortezomib 1.3 mg/m^2 subcutaneously on Days 1, 4, 8, and 11 during Cycles 1-6.; Dexamethasone 40 mg orally every week (20 mg on Days 1, 2, 8, 9, 15, and 16).; Daratumumab intravenously at a dose of 16 milligram per kilogram (mg/kg) weekly during induction treatment (Days 1, 8, and 15 of Cycles 1 through 4), and every 3 weeks during consolidation treatment (Day 1 of Cycles 5 and 6), followed by maintenance treatment with daratumumab every 4 or 8 weeks.
Intervention MeSH terms: Dexamethasone; Lenalidomide; Bortezomib; Daratumumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 224.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to determine if the addition of daratumumab to
      lenalidomide-bortezomib-dexamethasone (RVd) will increase the proportion of participants
      achieving stringent complete response (sCR), as defined by the International Myeloma Working
      Group (IMWG) criteria, by the time of completion of post autologous stem cell transplantation
      (ASCT) consolidation treatment, compared with RVd alone.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Considered by the investigator to be eligible for high-dose chemotherapy (HDT) and
             autologous stem cell transplantation (ASCT) according to the institution's criteria
             based on age, medical history, cardiac and pulmonary status, overall health and
             condition, co-morbid condition(s), physical examination, and laboratory studies

          -  Has not had prior systemic therapy for multiple myeloma. An emergency course of
             steroids (defined as no greater than 40 milligram [mg] of dexamethasone, or equivalent
             per day for a maximum of 4 days (that is, a total of 160 mg) is permitted. In
             addition, radiation therapy is permitted prior to study entry, during screening, and
             during Cycles 1-2 of study treatment as needed for lytic bone disease

          -  Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2

          -  Woman of childbearing potential must have 2 negative highly sensitive serum
             (beta-human chorionic gonadotropin [b-hCG]) during screening, the first one within 10
             to 14 days prior to the first dose of any component of study treatment and the second
             within 24 hours prior to the first dose of any component of study treatment

          -  A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted
             reproduction during the study (including during dose interruptions), and for 4 weeks
             following discontinuation of lenalidomide, and if receiving daratumumab, for 3 months
             after the last dose

        Exclusion Criteria:

          -  Diagnosed or treated for malignancy other than multiple myeloma, except: a) Malignancy
             treated with curative intent and with no known active disease present for more than
             equal to (>= )3 years before randomization; b) Adequately treated non-melanoma skin
             cancer, lentigo maligna or in situ malignancies (including but not limited to,
             cervical, breast) with no evidence of disease

          -  Exhibiting clinical signs of or has a known history of meningeal or central nervous
             system involvement by multiple myeloma

          -  Known chronic obstructive pulmonary disease with a forced expiratory volume in 1
             second (FEV1) less than (<)50 percent (%) of predicted normal

          -  Known moderate or severe persistent asthma within the past 2 years or currently has
             uncontrolled asthma of any classification

          -  Known to be seropositive for human immunodeficiency virus, known to have hepatitis B
             surface antigen positivity, or known to have a history of hepatitis C. Participants
             who completed treatment for hepatitis C at least 6 months prior to screening and have
             no detectable circulating hepatitis C virus (HCV) at screening, may participate in the
             study. Such participants will be required to undergo regular assessment for HCV
             reactivation during their participation in the study. Participants who test positive
             for HCV at any time during these assessments will be withdrawn from the study