Allogeneic Hematopoietic Stem Cell Transplantation With Ixazomib for High Risk Multiple Myeloma (BMT CTN 1302)

Eligible patients with a Human Leukocyte Antigen (HLA)-matched related or unrelated donor will undergo allogeneic hematopoietic stem cell transplant at Day 0. For GVHD prophylaxis, patients will be given Tacrolimus from Day -3 until at least 6 months following initiation, at an intravenous daily dose of 0.015 mg/kg. This will be combined with an intravenous administration of Methotrexate at 5 mg/m2 on Days +1, +3, +6, and +11.

Patients will receive conditioning treatment before and after HSCT. Fludarabine will be given at 30 mg/m2 intravenously on Day -6 through Day -3.

Melphalan will be given at 70 mg/m2 intravenously on Days -4 and -3.

Bortezomib will be administered at 1.3 mg/m2 intravenously on Day -3.

Between 60 and 120 days following HSCT, patients randomized to the experimental arm will receive Ixazomib maintenance. Maintenance will begin at 3-mg oral doses on Days 1, 8, and 15 of a 28-day cycle. This will increase to 4-mg doses on the same cycle schedule, following successful completion of 3 cycles at the previous dosage, for a total of 12 cycles.

Between 60 and 120 days following HSCT, patients randomized to the control group will be given 3 mg of placebo orally on Days 1, 8, and 15 of a 28-day cycle. This will increase to 4-mg doses on the same cycle schedule following successful completion of 3 cycles of placebo maintenance at the 3-mg dose. This will continue for a total of 12 cycles.