Allogeneic Nonmyeloablative Hematopoietic Stem Cell Transplant for Patients With BCR-ABL Tyrosine Kinase Inhibitor Responsive Ph+ Acute Leukemia - a Multi-Center Trial
I. To determine whether the rate of leukemia relapse can be decreased for patients with
chronic myelogenous leukemia in blast crisis (CML-BC) and philadelphia chromosome positive
acute lymphoblastic leukemia (Ph+ ALL) responsive to imatinib mesylate (or either dasatinib
or nilotinib for patients who have imatinib-resistant disease or who are intolerant of
imatinib) followed by nonmyeloablative hematopoietic stem cell transplantation (HSCT)
compared to historical controls given high-dose conventional allogeneic HSCT or
II. To determine whether the rate of transplantation-related mortality (TRM) can be
decreased for patients with CML-BC and Ph+ ALL responsive to imatinib mesylate (or dasatinib
or nilotinib) followed by nonmyeloablative HSCT compared to historical controls given
high-dose conventional allogeneic HSCT or chemotherapy.
I. To evaluate whether donor lymphocyte infusion (DLI) can be safely used in patients with
mixed or full donor chimerism as preemptive therapy to eliminate minimal residual disease.
INDUCTION THERAPY: Patients continue to receive imatinib mesylate orally (PO), dasatinib PO,
or nilotinib PO once or twice daily until day -2 and resume on day 14 or when blood counts
recover after peripheral blood stem cell (PBSC) transplantation.
NONMYELOABLATIVE CONDITIONING: Patients receive fludarabine intravenously (IV) on days -4 to
-2; and undergo TBI on day 0.
TRANSPLANTATION: Patients undergo allogeneic PBSC transplantation on day 0.
GRAFT-VERSUS-HOST-DISEASE (GVHD) PROPHYLAXIS: Patients receive mycophenolate mofetil (MMF)
PO every 12 hours on days 0-27 (related donor recipients) or every 8 hours on days 0-96 with
taper on day 40 (unrelated donor recipients). Patients also receive cyclosporine IV or PO
every 12 hours on days -3 to 56, followed by taper on days 57-180 (related donor recipients)
or on days -3 to 100, followed by taper on days 101-177 (unrelated donor recipients).
DONOR LYMPHOCYTE INFUSION: Patients with persistent disease and no GVHD after stopping GVHD
prophylaxis receive donor lymphocyte infusion IV over 30 minutes once every 28 days for 3
Treatment continues in the absence of disease progression or unacceptable toxicity.
Patients are followed up periodically for 2 years and then annually thereafter for 5 years.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Rate of relapse
Assessed up to 5 years
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
United States: Federal Government
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium||Seattle, Washington 98109|
|VA Puget Sound Health Care System||Seattle, Washington 98101|
|Presbyterian - Saint Lukes Medical Center - Health One||Denver, Colorado 80218|