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

Summary

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.

Timeline

Start

2019-04-16

Primary completion

2026-06-30

Completion

2027-09-15

Drugs

Indications