Clofarabine, Cytarabine, and Thymoglobulin for Allogeneic Transplantation
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.
Acute Myeloid Leukemia
Procedure: Stem cell infusion
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Non-Myeloablative Conditioning Regimen for Allogeneic Transplantation With Clofarabine, Cytarabine, and Thymoglobulin for Myelodysplastic Syndrome and Acute Myeloid Leukemia|
- To determine the six-month treatment related mortality for a conditioning regimen composed of clofarabine, cytarabine, and thymoglobulin for allogeneic transplantation of myelodysplastic syndromes and acute myeloid leukemia. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
- To describe the response rates for patients treated on this protocol. [ Time Frame: At one, three, six and twelve months. ] [ Designated as safety issue: No ]Disease-specific partial response and complete response. Also time-to-progression for responding patients.
- Determine percent donor chimerism achieved with this treatment [ Time Frame: At day +30, +60, and +90 ] [ Designated as safety issue: No ]
- Overall survival and disease-free survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
- Use conventional STR-PCR method for monitoring engraftment [ Time Frame: 5 years ] [ Designated as safety issue: No ]Includes assessment of mixed chimerism in the whole blood, myeloid cells, T cells, and B cells.
- Determine the acute and chronic graft-versus-host disease and other toxicities [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
|Study Start Date:||November 2007|
|Study Completion Date:||July 2009|
|Primary Completion Date:||December 2008 (Final data collection date for primary outcome measure)|
Clofarabine, Cytarabine and Thymoglobulin
Clofarabine 40mg/m2/day IV over two hours daily x 5 days on Days -6 thru -2.
Other Name: ClolarDrug: Cytarabine
Cytarabine 1gm/m2/day IV over two hours daily x 5 days on Days -6 thru -2 after the START of Clofarabine.
Other Names:Drug: Thymoglobulin
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.
Other Name: Anti-thymocyte globulinProcedure: Stem cell infusion
On day 0 a minimum of total CD34+ cell dose of 2 x10E6/kg (actual weight of recipient) will be infused.
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.
|United States, Missouri|
|Ravi Vij, M.D.|
|St. Louis, Missouri, United States, 63110|
|Principal Investigator:||Ravi Vij, M.D.||Washington Universtiy of St. Louis|