Daratumumab-bortezomib-dexamethasone (Dara-VCd) vs Bortezomib-Thalidomide-Dexamethasone (VTd), Then Maintenance With Ixazomib (IXA) or IXA-Dara

Sponsor
Stichting European Myeloma Network
Study ID
NCT03896737
Phase
PHASE2
Status
Active Not Recruiting

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - 65 Years
Healthy Volunteers
Not accepted

Interventions

  • Daratumumab plus Velcade Cyclophosphamide Dexamethasone — DRUG
    To compare Dara-VCd versus VTd as pre transplant induction and post transplant consolidation, both followed by a maintenance phase with Ixazomib alone or in combination with Daratumumab, in newly diagnosed Multiple Myeloma (MM) young patients eligible for autologous stem cell transplantation.
  • Velcade Thalidomide Dexamethasone — DRUG
    To compare Dara-VCd versus VTd as pre transplant induction and post transplant consolidation, both followed by a maintenance phase with Ixazomib alone or in combination with Daratumumab, in newly diagnosed Multiple Myeloma (MM) young patients eligible for autologous stem cell transplantation.

Study Details

This protocol is a phase II multicenter, randomized, open label study designed to assess the efficacy and safety of daratumumab combined with bortezomib, cyclophosphamide and dexamethasone (Dara-VCd) versus the association of bortezomib, thalidomide and dexamethasone (VTd) as pre transplant induction and post transplant consolidation, followed by maintenance with ixazomib alone or in combination with daratumumab, in newly diagnosed multiple myeloma (MM) patients eligible for autologous stem cell transplantation. Patients enrolled in the Dara-VCd arm will receive: 4 cycles of daratumumab-bortezomib-cyclophosphamide-dexamethasone induction, followed by transplantation and 2 cycles of daratumumab-bortezomib-cyclophosphamide-dexamethasone consolidation. The choice of cyclophosphamide in combination with bortezomib and dexamethasone is suggested by the better safety profile of cyclophosphamide, in comparison with thalidomide and the efficacy of the alkylator agent, when combined with bortezomib. Once-weekly bortezomib seems to be equally effective and better tolerated than the standard twice weekly schedule. The outcomes and response rate did not appear to be affected by the bortezomib dosing schedule. Patients enrolled in the VTd arm will receive: 4 cycles of bortezomib-thalidomide-dexamethasone induction, followed by autologous transplantation and 2 cycles of bortezomib-thalidomide dexamethasone as consolidation. The VTd drug association is the current standard first line induction therapy for multiple myeloma patients who are eligible to stem cell transplantation. At the end of consolidation phase patients with at least a partial response (≥ PR) will be rerandomized (assigned by chance) to one of 2 treatment groups to receive maintenance treatment with ixazomib alone or in combination with daratumumab. Patients will receive treatment until any sign of progression or intolerance, up to 24 months.

Key Dates

Start date
Apr 16, 2019
Status verified
Aug 2025
Primary completion
Jun 30, 2026
Completion
Feb 1, 2028

Study Design

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

Arms

  • Experimental: Dara-VCd
    treatment period includes administration of four 28-day cycles of induction with Dara- VCd; then patients will undergo transplant and finally they will receive two 28-day cycles of Dara-VCd consolidation treatment. The response will be assessed after each cycle. Patients in the first randomization will be stratified according to FISH (standard/missing vs high risk,defined as del17, t 4;14, t 14;16) and ISS (I vs II and III). TREATMENT SCHEMA - INDUCTION Daratumumab: 16 mg/Kg given by IV infusion on days 1, 8, 15, 22, on cycles 1-2 and on days 1, 15 on cycles 3-4. Bortezomib: 1.3 mg/m2 given SC injection on days 1, 8,15, 22; Cyclophosphamide: 300 mg/ m2 given orally or IV infusion on days 1, 8, 15, 22; Dexamethasone: 40 mg given orally or by IV infusion on days 1, 8, 15,22 Repeat for four 4-week induction cycles.
  • Active Comparator: VTd
    treatment period includes administration of four 28-day cycles of induction with VTd; then patients will undergo transplant and finally they will receive two 28-day cycles of VTd consolidation treatment. TREATMENT SCHEMA INDUCTION ARM VTd: Bortezomib: 1.3 mg/m2 given by SC injection on days 1, 4, 8, 11 of 28-day cycle; Thalidomide: 100 mg given orally on days 1-28. Dexamethasone: 20 mg given orally or by IV injection on days 1, 2, 3, 4, 8, 9, 10 and 11 of every 28-day cycle. Repeat for four 4-week induction cycles.

Primary Outcome Measure

Progression free survival (PFS) [ Time Frame: 5 years ]

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