At a glance
ClinicalIndex Comparison Record- ✓Age 18–70 years inclusive
- ✓Monoclonal plasma cells ≥10% in bone marrow or biopsy-proven plasmacytoma, plus ≥1 CRAB criterion or biomarker of malignancy
- ✓Measurable disease: serum M-protein ≥1.0 g/dL, urine M-protein ≥200 mg/24h, or serum free light chain ≥10 mg/dL with abnormal kappa/lambda ratio
- ✓Newly diagnosed, transplant-eligible for high-dose therapy and autologous stem cell transplantation
- ✕Prior or current systemic therapy or stem cell transplant for any plasma cell dyscrasia (except brief emergency corticosteroids ≤4 days)
- ✕Peripheral neuropathy or neuropathic pain Grade ≥2 (NCI-CTCAE v5)
- ✕Prior or concurrent invasive malignancy (other than MM) within 5 years of randomization (exceptions: adequately treated skin cancers, CIS cervix/breast, other non-invasive lesions)
- ✕Clinical signs of meningeal involvement of multiple myeloma
Standardized by ClinicalIndex from the ClinicalTrials.gov record · verify against the source.
A Phase 3 Study Comparing Daratumumab, VELCADE (Bortezomib), Lenalidomide, and Dexamethasone (D-VRd) vs VELCADE, Lenalidomide, and Dexamethasone (VRd) in Subjects With Previously Untreated Multiple Myeloma Who Are Eligible for High-dose Therapy
In Brief
A Phase 3 clinical trial evaluating Daratumumab, Velcade, and 2 other interventions for Multiple Myeloma. Active but no longer recruiting, targeting 709 participants across 13 sites in 13 countries.
Detailed Summary
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.
Study Details
Timeline
Interventions
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.
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 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 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.