Daratumumab, VELCADE (Bortezomib), Lenalidomide and Dexamethasone Compared to VELCADE, Lenalidomide and Dexamethasone in Subjects With Previously Untreated Multiple Myeloma

Sponsor
Stichting European Myeloma Network
Study ID
NCT03710603
Phase
PHASE3
Status
Active Not Recruiting

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - 70 Years
Healthy Volunteers
Not accepted

Interventions

  • Daratumumab — DRUG
    Daratumumab will be given at a dose of 1800 mg SC weekly in Cycles 1 and 2, then every 2 weeks in Cycles 3-6. In maintenance Cycles 7+, subjects will receive daratumumab once every 4 weeks until disease progression or unacceptable toxicity. MRD-negative subjects will stop daratumumab after sustained MRD negativity for 12 months \& after a min. of 24 months of maintenance. Daratumumab should be restarted at recurrence of MRD or confirmed loss of CR without disease progression.
  • Velcade — DRUG
    Bortezomib will be given at a dose of 1.3 mg/m2 SC twice a week (Days 1, 4, 8, and 11) in Cycles 1-6; four 28-day induction cycles (Cycles 1 to 4), and two 28-day consolidation cycles (Cycles 5-6). Subjects will not receive bortezomib after Cycle 6. On treatment days when both bortezomib and daratumumab are administered, bortezomib must be administered after the daratumumab administration.
  • Lenalidomide — DRUG
    Lenalidomide will be administered PO at 25 mg on Days 1 to 21 in Cycles 1-6; four 28-day induction cycles and two 28-day consolidation cycles. Following consolidation, subjects will then start maintenance therapy, during which they will receive lenalidomide 10 mg daily PO on Days 1 to 28 (continuously) of each 28-day cycle until disease progression or unacceptable toxicity. After 3 cycles of maintenance therapy, if well tolerated, the lenalidomide dose may be increased to 15 mg daily, at the discretion of the investigator.
  • dexamethasone — DRUG
    Dexamethasone will be administered PO at 40 mg daily on Days 1-4 and Days 9-12 of each 28-day cycle during induction and consolidation (Cycles 1-6). On daratumumab administration days, during induction/consolidation, dexamethasone may be administered intravenously 1 hour before the daratumumab administration. On days when daratumumab is not administered, dexamethasone is administered PO. Dexamethasone tablets are to be taken with or immediately after a meal or snack, preferably in the morning.

Study Details

Background of the study: The combination of daratumumab with VRd is anticipated to further improve response rates in patients and may lead to improved long-term outcomes in newly diagnosed patients with multiple myeloma. Given this potential, and based upon the initial safety and efficacy observed in the ongoing Phase 2 Study MMY2004, as well as continued positive results with daratumumab in various disease settings and combination regimens, this Phase 3 study is designed to demonstrate improved outcomes for patients treated with daratumumab+VRd. The Phase 3 study will utilize the subcutaneous (SC) formulation of daratumumab instead of the IV formulation utilized in the Phase 2 study, which may limit additional toxicity to patients treated with the quadruplet regimen.

Key Dates

Start date
Dec 14, 2018
Status verified
Jan 2026
Primary completion
Aug 1, 2023
Completion
Nov 30, 2029

Study Design

Enrollment
709 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Active Comparator: Velcade Lenalidomide dexamethasone (VRd)
    VRd: subjects will receive VRd for induction and consolidation, followed by lenalidomide (R) maintenance until disease progression or unacceptable toxicity.
  • Experimental: Daratumumab + VRd (D-VRd)
    D-VRd: Subjects will receive D-VRd for induction and consolidation followed by daratumumab and lenalidomide maintenance until disease progression or unacceptable toxicity. Minimal residual disease (MRD)-negative subjects in Arm B will stop therapy with daratumumab after sustained MRD negativity for 12 months and after a minimum of 24 months of maintenance therapy. These subjects will continue lenalidomide maintenance therapy until disease progression or unacceptable toxicity. After stopping daratumumab therapy, subjects with sustained MRD negativity should restart therapy with daratumumab if there is a recurrence of MRD or a confirmed loss of Complete Response (CR) without International Myeloma Working Group (IMWG)-defined disease progression. After reinitiating daratumumab, the subject will continue daratumumab and lenalidomide therapy until disease progression or unacceptable toxicity.

Primary Outcome Measure

Progression Free Survival (PFS) [ Time Frame: From the date of randomization to either progressive disease or death whichever occurred first, up to a maximum follow-up time of 54.41 months. ]

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