Clinical Trial: Combination Chemotherapy and Donor Stem Cell Transplant Followed by Ixazomib Citrate Maintenance Therapy in Treating Patients With Relapsed High-Risk Multiple Myeloma

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Feasibility Study of Myeloablative BEAM Allogeneic Transplantation Followed by Oral Ixazomib Maintenance Therapy in Patients With Relapsed High-Risk Multiple Myeloma

Brief Summary: This phase Ib trial studies the side effects of combination chemotherapy and donor stem cell transplant followed by ixazomib citrate maintenance therapy in treating patients with multiple myeloma that has returned after a period of improvement and is likely to recur (come back), or spread. Giving chemotherapy before a donor peripheral blood stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Giving ixazomib citrate after the transplant may improve the overall treatment outcome without causing additional toxicities.

Detailed Summary:

PRIMARY OBJECTIVES:

I. Safety of BEAM (carmustine, cytarabine, etoposide, melphalan) allogeneic transplant within 100 days, defined as the day 100 transplant related mortality (TRM).

II. Safety of oral ixazomib maintenance therapy from day 100 post allogeneic transplant up to 2 years, defined by the incidence of grade III-IV acute (or overlap) graft-versus-host disease (GvHD) and grade III-IV ixazomib related toxicity.

SECONDARY OBJECTIVES:

I. To assess the proportion of patients who are eligible to start ixazomib maintenance therapy.

II. To determine the incidence of discontinuation of ixazomib maintenance therapy at one and two years post initiation.

III. To determine response rates (complete response [CR], very good partial response [VGPR] and partial response [PR]) by day 100 and at 12 and 24 months after transplant.

IV. To determine two year progression-free survival and overall survival rate. V. To evaluate time to engraftment (defined by absolute neutrophil count [ANC] > 500 and platelets > 20,000).

TERTIARY OBJECTIVES:

I. To determine rates of minimal residual disease by deep sequencing (by ClonoSIGHT, Sequenta).

II. To estimate the cumulative incidence of disease progression rates. III. To determine rates of >= grade 3 toxicities using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

IV. To determine the incidence of treatment emergent peri
Sponsor: OHSU Knight Cancer Institute

Current Primary Outcome:

  • Incidence of grade III-IV acute (or overlap) GvHD and ixazomib related grade III-IV toxicity [ Time Frame: Up to 2 years ]
    Time to event analysis will be conducted to estimate the incidence of acute (or overlap) GvHD and grade III-IV treatment related toxicity among those who receive ixazomib maintenance therapy, accounting for possible competing risks and events. All treatment related toxicity will be tabulated and summarized by severity and major organ categories defined by the NCI CTCAE v. 4.0.
  • Transplant related mortality (TRM) [ Time Frame: Day 100 ]
    Time to event analysis will be conducted to estimate day 100 TRM and its confidence interval among those who receive BEAM allogeneic transplantation.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Incidence of discontinuation of ixazomib maintenance therapy [ Time Frame: At 1 year post initiation ]
    Reasons for discontinuation will be described.
  • Incidence of discontinuation of ixazomib maintenance therapy [ Time Frame: At 2 years post initiation ]
    Reasons for discontinuation will be described.
  • Overall survival [ Time Frame: At 2 years ]
  • Progression-free survival [ Time Frame: At 2 years ]
  • Proportion of patients who are eligible to start ixazomib maintenance therapy [ Time Frame: Up to day 180 post-transplant ]
    Exact 95% confidence interval will be reported.
  • Response rates (CR, VGPR, and PR) [ Time Frame: At day 100 ]
  • Response rates (CR, VGPR, and PR) [ Time Frame: At 12 months after transplant ]
  • Response rates (CR, VGPR, and PR) [ Time Frame: At 24 months after transplant ]
  • Time to engraftment (defined by ANC > 500 and platelets > 20,000) [ Time Frame: Up to 1 year ]


Original Secondary Outcome: Same as current

Information By: OHSU Knight Cancer Institute

Dates:
Date Received: July 20, 2015
Date Started: July 2015
Date Completion: July 2021
Last Updated: December 21, 2016
Last Verified: December 2016