Phase II Study of IRD (Ixazomib, Lenalidomide, Dexamethasone) Post Autologous Stem Cell Transplantation Followed by Maintenance Ixazomib or Lenalidomide for Multiple Myeloma

Based on the further need to improve progression-free survival and overall survival post-autologous stem cell transplantation (ASCT) for multiple myeloma and the benefits seen of consolidation/maintenance treatment with immunomodulatory drugs thalidomide and lenalidomide and the proteasome inhibitor bortezomib, the natural next step is to evaluate combination regimens of immunomodulatory drugs and proteasome inhibitors as consolidation/maintenance post-ASCT. The regimen consisting of ixazomib, lenalidomide, and dexamethasone (IRD) has been shown to have low toxicity, and the availability of an oral formulation of ixazomib allows for easier administration when compared to bortezomib. In this study, following consolidation with IRD, patients will be randomized to maintenance therapy with lenalidomide or ixazomib in order to collect pilot data comparing the toxicity and efficacy of maintenance therapy with immunomodulatory drugs and proteasome inhibitors. 09/23/2019: Following interim analysis 3 performed in August 2019, patients who were still in screening or in the consolidation phase of the trial were allowed to proceed with the consolidation study treatment. Following completion of consolidation, all patients were enrolled into the lenalidomide arm with the exception of those who discontinued lenalidomide during the consolidation phase due to toxicity. Patients who discontinued lenalidomide were allowed to be enrolled into the ixazomib arm following approval from the site-specific principal investigator and study-wide principal investigator. For patients previously randomized to ixazomib maintenance and continuing treatment, the patient and the respective treating physician were allowed to determine if the patient should remain on ixazomib or transition to the lenalidomide arm. Patients who were previously on lenalidomide maintenance and transitioned onto ixazomib due to toxicity were allowed to continue ixazomib maintenance. Patients who were on lenalidomide maintenance were continued unaltered. Once patients transitioned out of maintenance (to either transition lenalidomide or transition ixazomib), the patients were only followed for safety. 09/30/2021: Following analysis 4 in 2021, the consensus agreement was to allow patients to continue ixazomib at the discretion of the treating physician and with patient consent after being informed of the trial data. Those that continued transition ixazomib were only followed for safety.