Nonmyeloablative Allogeneic Hematopoietic Cell Transplantation From HLA Matched Sibling Donors For Treatment Of Patients With High Risk Acute Lymphocytic Leukemia In Complete Remission
- Determine if a one-year disease free survival of 40% and a day 200 transplant-related
mortality of less than 25% can be achieved in patients with high-risk acute
lymphoblastic leukemia in complete remission treated with a nonmyeloablative
conditioning regimen comprising fludarabine and total body irradiation followed by
allogeneic peripheral blood stem cell or bone marrow transplantation.
- Evaluate the efficacy and toxicity of donor lymphocyte infusion in the treatment of
minimal residual disease after nonmyeloablative allografting in these patients.
OUTLINE: This is a multicenter study.
Patients receive a nonmyeloablative conditioning regimen comprising fludarabine IV on days
-4 to -2 and total body irradiation (TBI) on day 0. Children undergo allogeneic peripheral
blood stem cell transplantation (PBSCT) or bone marrow transplantation after TBI on day 0.
Adults undergo filgrastim (G-CSF)-mobilized allogeneic PBSCT after TBI on day 0.
Patients also receive graft-versus-host disease (GVHD) prophylaxis therapy comprising oral
cyclosporine twice daily on days -3 to 56 and then tapered and oral mycophenolate mofetil
once at 5-10 hours after transplantation on day 0 and then twice daily on days 1-27.
Patients who have no evidence of grade 2 or greater acute GVHD or clinically extensive
chronic GVHD, have been off GVHD prophylaxis therapy for 1-2 weeks, and have stable or
increasing minimal residual disease after discontinuation of GVHD prophylaxis therapy
receive donor lymphocyte infusion (DLI) IV over 30 minutes. DLI repeats every 4 weeks for a
total of 3 doses (if necessary).
Patients without a history of CNS leukemia and patients with a history of CNS leukemia
previously treated with prophylactic craniospinal irradiation receive methotrexate (MTX) or
cytarabine (ARA-C) intrathecally (IT) for a total of 2 doses before transplantation and for
a total of 6 doses beginning on day 32 after transplantation. Patients with a history of CNS
leukemia not previously treated with craniospinal irradiation undergo craniospinal
irradiation for 11 days before conditioning regimen and then MTX or ARA-C IT for a total of
6 doses beginning on day 32 after transplantation. Male patients also undergo testicular
radiotherapy for 7 days.
Patients are followed at 1, 2, 3, 6, 12, 18, and 24 months.
PROJECTED ACCRUAL: A total of 30 patients (20 adults and 10 children) will be accrued for
this study within 2 years.
Masking: Open Label, Primary Purpose: Treatment
George Georges, MD
Fred Hutchinson Cancer Research Center
United States: Federal Government
|Fred Hutchinson Cancer Research Center||Seattle, Washington 98109|
|Cancer Institute at Oregon Health and Science University||Portland, Oregon 97201-3098|