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Conditioning With Targeted Busulfan, Cyclophosphamide and Thymoglobulin for Allogeneic Marrow or Peripheral Blood Stem Cell (PBSC) Transplantation for Myelodysplasia and Myeloproliferative Disorders
RATIONALE: Combining antithymocyte globulin with combination chemotherapy before donor peripheral stem cell transplantation may reduce the chance of developing graft-versus-host disease following transplantation. PURPOSE: Phase I/II trial to study the effectiveness of combining antithymocyte globulin with busulfan and cyclophosphamide in reducing graft-versus-host disease in patients who are undergoing donor stem cell transplantation for myelodysplastic syndrome or other myeloproliferative disorder.
OBJECTIVES: * Determine the incidence of acute graft-vs-host disease (GVHD) requiring therapy in patients with myelodysplastic syndromes or myeloproliferative disorders treated with busulfan, cyclophosphamide, and anti-thymocyte globulin prior to transplantation with filgrastim (G-CSF)-mobilized peripheral blood stem cells (or bone marrow) from related or unrelated donors. * Determine the incidence of relapse and relapse-free survival in patients treated with this regimen. * Determine the incidence of non-relapse mortality by day 100 and 1 year posttransplantation in patients treated with this regimen. * Determine the incidence of Epstein-Barr virus reactivation, infections, and chronic GVHD in patients treated with this regimen. OUTLINE: This is a dose-escalation study of anti-thymocyte globulin. * Conditioning and graft-vs-host disease (GVHD) prophylaxis: Patients receive oral busulfan every 6 hours on days -7 to -4 (16 doses), cyclophosphamide IV on days -3 and -2, and anti-thymocyte globulin IV over 3 hours on days -3, -2, and -1. Cohorts of 15 patients receive adjusted doses of anti-thymocyte globulin to determine the optimal dose at which Epstein-Barr virus (EBV) activation and GVHD are reduced. The optimal dose is the dose at which 2 consecutive cohorts receive the same regimen. * Stem cell transplantation: Patients undergo peripheral blood stem cell (PBSC) or bone marrow transplantation on day 0. * Posttransplantation GVHD prophylaxis: Patients receive cyclosporine IV continuously on days -1 to 4 and then orally twice daily until day 180. Patients also receive methotrexate on days 1, 3, 6, and 11. Patients are followed every 6 months for 2 years and then annually thereafter. PROJECTED ACCRUAL: A total of 30-45 patients will be accrued for this study within 2 years.
Age
0 - 65 years
Sex
ALL
Healthy Volunteers
No
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States
Start Date
October 1, 2002
Completion Date
September 1, 2006
Last Updated
May 14, 2010
anti-thymocyte globulin
BIOLOGICAL
busulfan
DRUG
cyclophosphamide
DRUG
cyclosporine
DRUG
methotrexate
DRUG
allogeneic bone marrow transplantation
PROCEDURE
peripheral blood stem cell transplantation
PROCEDURE
Lead Sponsor
Fred Hutchinson Cancer Center
Collaborators
NCT00106925
NCT06311227
Data Source & Attribution
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