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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Given IV
Given IV
Given IV
Given IV
Given PO or IV
Given PO
Given SC
Undergo total-body irradiation
Undergo allogeneic bone marrow transplantation
Correlative studies
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States
Overall Survival (OS)
Will be analyzed using Kaplan-Meier (KM) method, and OS will be obtained from the KM estimates along with 95% confidence intervals.
Time frame: Day 100
Time to Neutrophil Recovery
Defined as achieving an absolute neutrophil count (ANC) greater than or equal to 500/ul for three consecutive measurements on different days. 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.
Time frame: Up to 1 year
Percentage of Participants With Platelet Recovery by Day 30
Platelet recovery is defined as the first day of a platelet count greater than 20,000/mm\^3 with no platelet transfusions. 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.
Time frame: Up to day 30
Number of Participants With 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. Will be analyzed using KM method.
Time frame: Day 30
Cumulative Incidence of Grade III-IV Acute GVHD
Determined by the standard bone marrow transplant (BMT) Clinical Trials Network criteria (BMTCTN). Will be analyzed using KM method, a Graft versus Host Disease (GVHD) grade III-IV will be obtained from the KM estimates along with 95% confidence intervals.
Time frame: Day 100
Cumulative Incidence of Chronic GVHD According to BMTCTN
Will be summarized with a proportion and a 95% confidence interval.
Time frame: Up to 1 year
Number of Participants With Complete Remission After Transplantation
Time frame: Up to 1 year
Progression Free Survival
Time frame: Up to 1 year
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