This study will test the combination of clofarabine, cytarabine, and thymoglobulin as a non-myeloablative conditioning regimen for patients with myelodysplastic syndromes or acute myeloid leukemia undergoing allogeneic stem cell transplant.
Current reduced intensity conditioning regimens have been able to decrease TRM (treatment related mortality) but suffer from increased rates of disease relapse. Disease burden at transplantation, as measured by percent myeloblasts, predicts relapse. Current regimens employ fludarabine and busulfan with various adjutants, but these agents are not part of the usual armamentarium used versus leukemia and have questionable anti-leukemic activity. By substituting clofarabine and cytarabine, a combination with proven anti-leukemic activity in the relapsed and refractory setting as well as activity versus MDS, as the back bone of the regimen we hope overcome residual disease and improve post-transplant relapse rates. Furthermore the principal toxicity of this regimen is myelosuppression, which should be abrogated by the infusion of stem cells. Thymoglobulin is included due to its minimal contribution to toxicity but significant benefits in engraftment, and controlling acute and chronic GVHD, which are major contributors to TRM and disease specific activity in MDS.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
7
Ravi Vij, M.D.
St Louis, Missouri, United States
Six-month Treatment Related Mortality
Time frame: 6 months
Disease Specific Response Rates
Disease-specific partial response and complete response.
Time frame: One, three, six and twelve months.
Engraftment as Measured by Percent Donor Chimerism
Time frame: Day +30
Engraftment as Measured by Percent Donor Chimerism
Time frame: Day +40-+60
Engraftment as Measured by Percent Donor Chimerism
Time frame: Day +80-+90
Overall Survival
Time frame: 5 years from time of restaging
Disease-free Survival
Disease-free survival is defined as the length of time after treatment ends that the participant survives without any signs or symptoms of that cancer.
Time frame: 5 years from time of restaging
Rate of Acute Graft-versus-host Disease (GVHD)
Acute GVHD occurs within 100 days of transplant.
Time frame: Up to 100 days after transplant
Rate of Chronic Graft-versus-host Disease (GVHD)
Time frame: 100 days-1 year after transplant
Use Conventional STR-PCR Method for Monitoring Engraftment
Includes assessment of mixed chimerism in the whole blood, myeloid cells, T cells, and B cells.
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Time frame: Up to 1 year after transplant
Median Time to Progression
Time to progression is defined as the length of time from the start of treatment until the disease starts to get worse or spread to other parts of the body.
Time frame: 5 years from time of restaging