Conditioning For Hematopoietic Cell Transplantation With Fludarabine Plus Targeted IV Busulfan and GVHD Prophylaxis With Thymoglobulin, Tacrolimus and Methotrexate in Patients With Myeloid Malignancies
- Determine the incidence and severity of acute graft-versus-host disease (GVHD) in
patients with myeloid malignancies treated with conditioning regimen comprising
fludarabine phosphate and busulfan followed by allogeneic peripheral blood stem cell
transplantation and GVHD prophylaxis comprising antithymocyte globulin, tacrolimus, and
- Determine the incidence of donor engraftment in patients treated with this regimen.
- Determine the pharmacokinetics of IV busulfan, including interdose variability and
evaluation of a limited sampling strategy, in these patients.
- Determine the pharmacokinetics of antithymocyte globulin in these patients.
- Determine the pharmacokinetics of fludarabine phosphate and its effect on lymphocytes
in these patients.
- Determine the incidence of specific toxic effects ≥ grade 3 in patients treated with
- Determine the incidence and severity of chronic GVHD in these patients.
- Determine the incidence of nonrelapsing mortality at 100 days and at 1 year after
transplantation in these patients.
- Determine the incidence of relapse in these patients.
- Determine relapse-free survival of these patients.
- Determine the incidence of Epstein-Barr virus activation in these patients.
- Conditioning regimen: Patients receive fludarabine phosphate IV over 30 minutes on days
-6 to -2 and busulfan IV over 3 hours on days -5 to -2. Prior to the conditioning
regimen, patients whose cerebrospinal fluid is positive for malignant cells receive
intrathecal methotrexate or cranial irradiation for CNS prophylaxis.
- Allogeneic peripheral blood stem cell (PBSC) transplantation: Patients receive
filgrastim (G-CSF)-mobilized allogeneic PBSCs IV on day 0.
- Graft-versus-host disease prophylaxis: Patients receive antithymocyte globulin IV over
at least 10 hours on days -3 to -1. They also receive tacrolimus orally twice daily or
IV continuously beginning on day -1 and continuing until up to day 55, followed by a
taper until day 180 in the absence of graft-versus-host disease. Patients also receive
methotrexate IV on days 1, 3, 6, and 11.
After completion of study treatment, patients are followed annually.
PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.
Masking: Open Label, Primary Purpose: Treatment
Incidence and severity of acute graft-versus-host disease (GVHD)
Paul V. O'Donnell, MD, PhD
Fred Hutchinson Cancer Research Center
United States: Federal Government
|Fred Hutchinson Cancer Research Center||Seattle, Washington 98109|