Conditions: Myelodysplastic Syndromes Acute Myeloid Leukemia
Keywords: Conditioning regimens Stem Cell Transplantation Hematopoietic Stem Cell Transplantation Allogeneic Stem Cell Transplantation Nonmyeloablative conditioning Clofarabine Cytarabine Anti-thymocyte globulin
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 7
Healthy volunteers: no

Brief summary:
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.

Detailed description:
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.

Arms:
arm 1: * Clofarabine 40mg/m2/day IV over two hours daily x 5 days on Days -6 thru -2
* Cytarabine 1gm/m2/day IV over two hours daily x 5 days on Days -6 thru -2 after the START of Clofarabine.
* Thymoglobulin 1.0mg/kg IV over 6 hours X 1 day on Day -4, then 2.5mg/kg/day x 2 days on Days -3 and -2.
* Stem Cell Transplant - On day 0 a minimum of total CD34+ cell dose of 2 x10E6/kg (actual weight of recipient) will be infused.

Interventions: intervention 1: Clofarabine intervention 2: Cytarabine intervention 3: Thymoglobulin intervention 4: Stem cell infusion
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None intervention 4: None

Protocol document: