Cyclophosphamide and Anti-thymocyte Globulin Followed By Methotrexate and Cyclosporine in Preventing Chronic Graft-Versus-Host Disease in Patients With Severe Aplastic Anemia Undergoing Donor Bone Marrow Transplant
|Aplastic Anemia||Drug: cyclophosphamide Biological: anti-thymocyte globulin Drug: cyclosporine Procedure: allogeneic bone marrow transplantation Drug: methotrexate Genetic: DNA analysis Other: flow cytometry Genetic: polymorphism analysis Other: laboratory biomarker analysis||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Cyclophosphamide and Antithymocyte Globulin Conditioning Regimen for Marrow Transplantation From HLA-Matched Family Members for Severe Aplastic Anemia: Effect of Marrow Cell Dose on Chronic Graft-vs.-Host Disease: A Multi-Center Trial|
- Incidence of Chronic GVHD [ Time Frame: 2 years ]Analyzed using cumulative incidence estimates, treating death or rejection as competing risk events.
- Number of Days to Neutrophil Recovery to >500/uL [ Time Frame: 100 days post-transplant ]First of 3 consecutive days of neutrophils >500/uL
- Overall Survival [ Time Frame: From the time of enrollment until death from any cause up to one year ]Number of patients alive at one year
|Study Start Date:||February 2006|
|Study Completion Date:||August 2012|
|Primary Completion Date:||May 2012 (Final data collection date for primary outcome measure)|
Experimental: Treatment (conditioning regimen, transplant, GVHD prophylaxis)
Patients receive a conditioning regimen comprising cyclophosphamide IV on days -5 to -2 and anti-thymocyte globulin IV over 4-10 hours on days -4 to -2. Patients undergo allogeneic bone marrow transplantation on day 0. Patients then receive GVHD prophylaxis comprising methotrexate IV on days 1, 3, 6, and 11 and cyclosporine IV over 1 hour or PO twice daily on days -1 to 50, followed by a taper until 6 months after grafting.
Other Names:Biological: anti-thymocyte globulin
Other Names:Drug: cyclosporine
Given IV or PO
Other Names:Procedure: allogeneic bone marrow transplantation
Undergo allogeneic bone marrow transplantation
Other Names:Drug: methotrexate
Other Names:Genetic: DNA analysis
Correlative studiesOther: flow cytometry
Correlative studiesGenetic: polymorphism analysis
Correlative studiesOther: laboratory biomarker analysis
I. Minimize the incidence of chronic GVHD by restricting the transplanted marrow dose to 2.0-2.5 x 10^8 nucleated cells/kg.
I. Engraftment and overall survival.
CONDITIONING REGIMEN: Patients receive cyclophosphamide intravenously (IV) on days -5 to -2 and anti-thymocyte globulin IV over 4-10 hours on days -4 to -2.
TRANSPLANTATION: Patients undergo allogeneic bone marrow transplantation on day 0.
GVHD PROPHYLAXIS: Patients receive methotrexate IV on days 1, 3, 6, and 11 and cyclosporine IV over 1 hour or orally (PO) twice daily on days -1 to 50, followed by a taper until 6 months after grafting.
After completion of study treatment, patients are followed up at on day 180, 1 year, 1.5 years, 2 years, 3 years, and yearly thereafter.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00343785
|United States, Utah|
|Huntsman Cancer Institute/University of Utah|
|Salt Lake City, Utah, United States, 84112|
|United States, Washington|
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|
|Seattle, Washington, United States, 98109|
|United States, Wisconsin|
|Froedtert and the Medical College of Wisconsin|
|Milwaukee, Wisconsin, United States, 53226|
|Principal Investigator:||Rainer Storb||Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|