Fludarabine and Low-Dose TBI Dose Escalation to Determine the Optimal Regimen for Achieving High Rates Engraftment of Unrelated Donor Peripheral Blood Stem Cell in Patients With Chronic Myeloid Leukemia - A Multi-Center Trial
- Determine whether increasing the intensity of a nonmyeloablative conditioning regimen
comprising fludarabine and total body irradiation allows achievement of a donor T-cell
chimerism level of > 40% on day 28 post-transplantation in 90% or more of patients with
chronic myelogenous leukemia undergoing allogeneic peripheral blood stem cell
transplantation and immunosuppression comprising cyclosporine and mycophenolate
- Determine the feasibility of reducing the day 84 graft rejection rate/graft failure to
< 10% in patients treated with this regimen.
- Determine the feasibility of maintaining the incidence of grade 4 acute
graft-versus-host disease at < 10% in patients treated with this regimen.
- Determine the feasibility of maintaining the day 200 nonrelapse mortality rate at < 15%
in patients treated with this regimen.
- Determine the rate of complete cytogenetic remission in patients treated with this
- Determine the probability of actuarial disease-free survival of patients treated with
- Determine the pharmacokinetics of mycophenolate mofetil and fludarabine in these
OUTLINE: This is a multicenter, dose-escalation study of fludarabine and total-body
- Nonmyeloablative conditioning regimen: Patients receive fludarabine IV on days -4 to -2
OR days -6 to -2. Patients undergo TBI on day 0.
- Allogeneic peripheral blood stem cell transplantation (PBSCT): After the completion of
TBI, patients undergo allogeneic PBSCT on day 0.
- Immunosuppression: Patients receive oral cyclosporine twice daily on days -3 to 100
followed by a taper to day 177 in the absence of graft-versus-host disease (GVHD).
Beginning within 4-6 hours after the completion of PBSCT, patients receive oral
mycophenolate mofetil 2-3 times daily on days 0-40 followed by a taper to day 96 in the
absence of GVHD.
Cohorts of 5-25 patients receive cumulative doses of fludarabine and escalating doses of TBI
until 2 of 5, 3 of 10-15, 4 of 20, or 5 of 25 patients experience a day 28 post-transplant
T-cell chimerism level ≤ 40% and/or a day 84 post-transplant graft rejection rate of > 10%.
After completion of study transplantation, patients are followed 3 times weekly for 3
months, at 6, 12, and 18 months, annually for 5 years, and then periodically thereafter.
PROJECTED ACCRUAL: A total of 5-75 patients will be accrued for this study.
Primary Purpose: Treatment
Increase number of patients with donor T-cell chimerism from > 40% to 90% on day 28 post-transplant
Brenda Sandmaier, MD
Fred Hutchinson Cancer Research Center
United States: Federal Government
|Fred Hutchinson Cancer Research Center||Seattle, Washington 98109|
|Veterans Affairs Medical Center - Seattle||Seattle, Washington 98108|
|Seattle Cancer Care Alliance||Seattle, Washington 98109|