Allogeneic Hematopoietic Stem Cell Transplantation With Ixazomib for High Risk Multiple Myeloma (BMT CTN 1302)
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Study type: Interventional
Phase: Phase 2

Summary: 
      This study is designed to compare progression-free survival (PFS) from randomization among
      patients randomized on the BMT CTN 1302 protocol, "Multicenter Phase II, Double-blind Placebo
      Controlled Trial of Maintenance Ixazomib after Allogeneic Hematopoietic Stem Cell
      Transplantation for High Risk Multiple Myeloma". It is hypothesized that Ixazomib maintenance
      therapy will result in improved PFS in patients with high-risk multiple myeloma following
      Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) compared to placebo.
    

Detailed description: 
      The study is designed as a Phase II, multi-center double-blind trial that randomizes patients
      with high risk Multiple Myeloma to Ixazomib maintenance or placebo 60-120 days after
      allogeneic HSCT. The primary objective of this randomized trial is to compare progression
      free survival from randomization as a time to event endpoint between patients randomized to
      Ixazomib maintenance or placebo. Secondary objectives are to describe for each treatment arm:
      rates of grade II-IV and III-IV Graft-Versus-Host-Disease (GVHD), chronic GVHD, best disease
      response rates, disease progression, transplant related mortality, overall survival, rates of
      Grade ≥ 3 toxicity according to the Common Terminology Criteria for Adverse Events (CTCAE)
      Version 4.0, incidence of infections, and health-related quality of life.
    

Intervention name(s): Allogeneic HSCT; Fludarabine; Melphalan; Bortezomib; Ixazomib; Placebo
Intervention type(s): Procedure; Drug; Drug; Drug; Drug; Drug
Intervention description(s): 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.
Other intervention name(s): Allogeneic hematopoietic stem cell transplant; Fludara; Alkeran; Velcade®; MLN9708; Ninlaro; sugar pill
Intervention MeSH terms: Fludarabine; Bortezomib; Melphalan; Ixazomib
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Multiple Myeloma; Allogeneic Transplant; Maintenance Therapy; Anti-Myeloma Agents; Hematologic Disorders