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
This clinical trial is studying how well giving cyclophosphamide together with anti-thymocyte globulin followed by methotrexate and cyclosporine works in preventing chronic graft-vs-host disease (GVHD) in patients with severe aplastic anemia undergoing donor bone marrow transplant. Giving low doses of chemotherapy, such as cyclophosphamide, before a donor bone marrow transplant helps stop the growth of abnormal cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining abnormal cells. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving anti-thymocyte globulin before and methotrexate and cyclosporine after transplant may stop this from happening
Biological: anti-thymocyte globulin
Procedure: allogeneic bone marrow transplantation
Genetic: DNA analysis
Other: flow cytometry
Genetic: polymorphism analysis
Other: laboratory biomarker analysis
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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 ] [ Designated as safety issue: No ]Analyzed using cumulative incidence estimates, treating death or rejection as competing risk events. Confidence intervals will be calculated using the method described by Marubini and Valsecchi (1995). Risk factors for the development of chronic GVHD will be evaluated using Cox regression analyses methods.
- Engraftment [ Time Frame: 100 days post-transplant ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: From the time of enrollment until death from any cause, assessed up to approximately 6 years ] [ Designated as safety issue: No ]
|Study Start Date:||February 2006|
|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|