The purpose of this study is to determine whether 5-Azacytidine priming before the conditioning regimen for subjects receiving a hematopoietic stem cell transplant is an effective treatment for high risk myeloid malignancies in complete remission (CR).
This open label two-step phase II study is designed to determine the safety and efficacy of epigenetic priming with 5-Azacytidine immediately prior to reduced intensity conditioning for an in vivo T-cell depleted hematopoietic stem cell transplantation for high risk myeloid malignancies in complete remission (CR). Subjects will be given a five day course of subcutaneous 5-azacytidine, followed by a reduced intensity conditioning regimen of fludarabine, melphalan and total body irradiation (TBI) prior to an allogeneic hematopoietic stem cell transplantation from a related or unrelated Human Leukocyte Antigen (HLA) matched donor. The effect of 5-azacytidine on global gene methylation will be assessed. Evaluations for safety, in particular for graft failure, transplant related mortality and acute graft versus host disease will be made on a weekly basis. Efficacy, as defined by disease free survival, will be evaluated with a bone marrow biopsy at the standard time points, which are one-, three-, six-, and twelve-months after transplant and upon clinical suspicion within regular follow-up visits - weekly for the first 3 months, then biweekly for 3 months, then monthly until one-year post-stem cell transplant. Thereafter, unless otherwise dictated by the clinical scenario, the follow up visits will be every 3 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
40
Patients will be given a five day course of subcutaneous 5-azacytidine followed by a reduced intensity conditioning regimen of fludarabine and melphalan with or without total body irradiation prior to an allogeneic hematopoietic stem cell transplantation from a related or unrelated HLA matched donor. 5-Azacytidine 75 mg/m2 subcutaneously daily at the same time on days -11, -10, -9, -8 and -7. This will be administered on an outpatient basis if possible.
Conditioning regimen: Hospital admission will usually take place on the first day of the conditioning regimen. Fludarabine will be given at 40 mg/m2 intravenously daily at the same time over 30 minutes on days -6,-5,-4,-3.
Conditioning regimen: Hospital admission will usually take place on the first day of the conditioning regimen. Melphalan will be given at 140 mg/m2 IV on day -3.
Weill Cornell Medical College
New York, New York, United States
Disease Free Survival at 1 Year Post-transplant
Number of participants without evidence of progression of underlying malignancy for which the transplant was performed, assessed at 1 year post-transplant.
Time frame: 1 year post-transplant
Disease Free Survival at 6 Months Post-transplant
Number of participants without evidence of progression of underlying malignancy for which the transplant was performed, assessed at 6 months post-transplant
Time frame: 6 months post-transplant
Disease Free Survival at 2 Years Post-transplant
Number of participants without evidence of progression of underlying malignancy for which the transplant was performed, assessed at 2 years post-transplant.
Time frame: 2 years post-transplant
Overall Survival at 6 Months Post-transplant
Number of participants alive at 6 months post-transplant
Time frame: 6 months post-transplant
Overall Survival at 1 Year Post-Transplant
Number of participants alive at 1 year post-transplant
Time frame: 1 year post-transplant
Overall Survival at 2 Years Post-Transplant
Number of participants alive at 2 years post-transplant
Time frame: 2 years post-transplant
Graft Failure
Number of patients who experience graft failure, defined as the absence of neutrophil engraftment by Day +21 or a drop in the absolute neutrophil count to \<0.3 cells/microL for five consecutive days occurring after initial neutrophil engraftment within the first 3 weeks post-transplantation.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Conditioning regimen: Hospital admission will usually take place on the first day of the conditioning regimen. Alemtuzumab will be given at 30 mg subcutaneously on Days -4 and -2 for unrelated donors, and Day -2 for related donors.
Conditioning regimen: Hospital admission will usually take place on the first day of the conditioning regimen. Total Body Irradiation (TBI) will be given at 2 doses of 200 cGy each on one day of the conditioning regimen (between days -6 and -3).
Time frame: 21 days post-transplant
Acute Graft-versus-Host Disease (GVHD)
Number of patients who develop acute graft-versus-host disease of any grade.
Time frame: 2 years post-transplant
High-Risk Extensive Chronic Graft-versus-Host-Disease
Number of patients who develop high-risk extensive chronic graft-versus-host disease. Extensive chronic GVHD is defined as generalized skin or multiple organ involvement. High risk chronic GVHD is defined as platelet count of less than 100k/microL
Time frame: 2 years post-transplant