A Multi-center Phase II Study of Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts for the Prevention of GVHD
- Estimate the probability of grades II-IV acute graft-vs-host disease (GVHD) in patients
with acute leukemia or advanced myelodysplastic syndromes treated with CD45RA+
T-cell-depleted allogeneic peripheral blood stem cell transplantation and compare this
to relevant historical experience.
- Estimate the probability of graft failure in these patients.
- Evaluate immune reconstitution and pathogen-specific T-cell reconstitution in these
- Estimate the probability of transplant-related mortality by day 100 in these patients.
- Estimate the probability of relapse in these patients.
- Estimate the probability and severity of chronic GVHD in these patients.
OUTLINE: This is a multicenter study.
- Myeloablative conditioning regimen: Patients undergo total body irradiation twice daily
for 4 days (Days -10 to -7) Patients also receive thiotepa IV over 4 hours for 2 days
(Days -6 and -5) and fludarabine phosphate IV over 30 minutes for 5 days (Days -6 to
- Transplantation: Patients receive a CD34+ enriched allogeneic peripheral blood stem
cell (PBSC) product followed by a CD45RA+ T-cell-depleted allogeneic PBSC product on
- Graft-vs-host disease (GVHD) prophylaxis: Patients will receive Tacrolimus as per
cohort 1. If the rate of grade II-IV acute GVHD in the first 35 patients is
significantly reduced (compared to historical controls), subsequent patients are
enrolled in cohort 2.
- Cohort 1: Patients receive tacrolimus IV continuously or orally twice daily
beginning on day -1 and continuing until day 50, followed by a standard taper in
the absence of grade II-IV acute GVHD.
- Cohort 2: Patients receive tacrolimus IV continuously or orally twice daily
beginning on day -1 and continuing until day 30, followed by a rapid taper in the
absence of grade II-IV acute GVHD.
Patients are followed actively for at least 1 year post transplant.
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Rate of grade II-IV acute graft-vs-host disease (GVHD)
Start of study to day 100
Marie Bleakley, MD
Fred Hutchinson Cancer Research Center
United States: Food and Drug Administration
|Fred Hutchinson Cancer Research Center||Seattle, Washington 98109|
|Yale University School of Medicine/Yale New Haven Hospital||New Haven, Connecticut 06520|