Clinical Trial: Decitabine and Total-Body Irradiation Followed By Donor Bone Marrow Transplant and Cyclophosphamide in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Decitabine Followed by Bone Marrow Transplant and High-Dose Cyclophosphamide for the Treatment of Relapsed and Refractory Acute Myeloid Neoplasms

Brief Summary: This phase II trial studies how well decitabine and total-body irradiation followed by donor bone marrow transplant and cyclophosphamide works in treating patients with relapsed or refractory acute myeloid leukemia. Giving decitabine and total-body irradiation before a donor bone marrow transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem 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. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving decitabine and total-body irradiation before the transplant together with high-dose cyclophosphamide, tacrolimus, and mycophenolate mofetil after the transplant may stop this from happening.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To determine overall survival at 100 days after transplantation following decitabine and a bone marrow transplant using a donor that is at least partially-matched and a myeloablative preparative regimen with post-transplantation cyclophosphamide for graft-versus-host disease (GVHD) prophylaxis.

SECONDARY OBJECTIVES:

I. Patients enrolled in this study will also be followed for the following endpoints: neutrophil and platelet recovery, graft failure, acute graft-versus-host disease (GVHD), chronic GVHD, incidence of infection, treatment-related mortality, time to relapse/progression, overall survival, and progression-free survival.

OUTLINE:

Beginning between days -29 and -22, patients receive decitabine intravenously (IV) over 1 hour daily for 10 days, fludarabine phosphate IV over 30 minutes on days -5 to -2, and busulfan IV over 3 hours on days -5 to -2.

PREPARATIVE REGIMEN: Patients undergo total-body irradiation twice daily (BID) on day -1.

TRANSPLANT: Patients undergo allogeneic bone marrow transplant on day 0.

GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV over 2 hours on days 3 and 4, tacrolimus orally (PO) BID or IV continuously on days 5-180, mycophenolate mofetil PO three times daily (TID) on days 5-35 and filgrastim subcutaneously (SC) beginning day 5 until absolute neutrophil count (ANC) >= 1,000/mm^3 for 3 consecutive days.

After completion of study treatment, patients are followed up at 6 months and 1 year.


Sponsor: University of Wisconsin, Madison

Current Primary Outcome: Overall survival [ Time Frame: Day 100 ]

Will be analyzed using Kaplan-Meier (KM) method, and OS will be obtained from the KM estimates along with 95% confidence intervals.


Original Primary Outcome: Overall survival [ Time Frame: 100 days ]

The primary objective is to determine overall survival at 100 days after transplantation following decitabine and a HLA-haploidentical bone marrow transplantation using a myeloablative preparative regimen and post-transplantation cyclophosphamide.


Current Secondary Outcome:

  • Neutrophil recovery defined as achieving an absolute neutrophil count (ANC) greater than or equal to 500/ul for three consecutive measurements on different days [ Time Frame: Up to 1 year ]
    Will be summarized with mean and standard deviation or median and interquartile range, and the change will be tested using a one-sample paired t-test at a two-tailed significance level of 0.05.
  • Platelet recovery defined as the first day of a platelet count greater than 20,000/mm^3 with no platelet transfusions in the preceding 7 days [ Time Frame: Up to 1 year ]
    Will be summarized with mean and standard deviation or median and interquartile range, and the change will be tested using a one-sample paired t-test at a two-tailed significance level of 0.05.
  • Primary graft failure defined as less than 5% donor chimerism in the cluster of differentiation (CD)3 and CD33 selected cell populations at any time after transplantation [ Time Frame: Day 30 ]
    Will be analyzed using KM method.
  • Cumulative incidence of grade III-IV acute GVHD determined by the standard bone marrow transplant (BMT) Clinical Trials Network criteria (BMTCTN) [ Time Frame: Day 100 ]
    Will be analyzed using KM method, aGVHD grade III-IV will be obtained from the KM estimates along with 95% confidence intervals.
  • Cumulative incidence of chronic GVHD according to BMTCTN [ Time Frame: Up to 1 year ]
    Will be summarized with a proportion and a 95% confidence interval.
  • Complete remission after transplantation [ Time Frame: Up to 1 year ]
  • Time to relapse/progression [ Time Frame: Up to 1 year ]


Original Secondary Outcome:

  • Neutrophil recovery [ Time Frame: 12 months ]
    Patients enrolled in this study will also be followed for the following endpoints: neutrophil recovery.
  • Assessment of graft failure [ Time Frame: 12 months ]
    Patients enrolled in this study will also be followed for the following endpoints: Graft failure.
  • Asessment of Acute GVHD and Chronic GVHD [ Time Frame: 12 months ]
    Patients enrolled in this study will also be followed for the following endpoints: Acute graft-versus-host disease (GVHD)and chronic GVHD.
  • Incidence of infection [ Time Frame: 12 months ]
    Patients enrolled in this study will also be followed for the following endpoints: Incidence of infection.
  • Treatment-related mortality [ Time Frame: 12 months ]
    Patients enrolled in this study will also be followed for the following endpoints: Treatment-related mortality.
  • Platelet recovery [ Time Frame: 12 months ]
    Patients enrolled in this study will also be followed for the following endpoints: platelet recovery.
  • Time to relapse/progression [ Time Frame: 12 months ]
    Patients enrolled in this study will also be followed for the following endpoints: Time to relapse/progression.
  • Overall patient survival [ Time Frame: 12 months ]
    Patients enrolled in this study will also be followed for the following endpoints: Overall survival.
  • Progression-free survival [ Time Frame: 12 months ]
    Patients enrolled in this study will also be followed for the following endpoints: Progression-free survival.


Information By: University of Wisconsin, Madison

Dates:
Date Received: October 8, 2012
Date Started: May 2013
Date Completion: May 2018
Last Updated: January 9, 2017
Last Verified: January 2017