Fludarabine Phosphate and Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemia or Chronic Myelogenous Leukemia That Has Responded to Treatment With Imatinib Mesylate, Dasatinib, or Nilotinib
|Adult Acute Lymphoblastic Leukemia in Remission Blastic Phase Chronic Myelogenous Leukemia Childhood Acute Lymphoblastic Leukemia in Remission Chronic Myelogenous Leukemia, BCR-ABL1 Positive Chronic Phase Chronic Myelogenous Leukemia Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia Philadelphia Chromosome Positive Childhood Precursor Acute Lymphoblastic Leukemia Recurrent Adult Acute Lymphoblastic Leukemia Recurrent Childhood Acute Lymphoblastic Leukemia Relapsing Chronic Myelogenous Leukemia||Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation Drug: imatinib mesylate Drug: dasatinib Drug: nilotinib Radiation: total-body irradiation Drug: cyclosporine Drug: mycophenolate mofetil Drug: fludarabine phosphate Procedure: peripheral blood stem cell transplantation Biological: therapeutic allogeneic lymphocytes||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Allogeneic Nonmyeloablative Hematopoietic Stem Cell Transplant for Patients With BCR-ABL Tyrosine Kinase Inhibitor Responsive Ph+ Acute Leukemia - a Multi-Center Trial|
- Rate of relapse [ Time Frame: Assessed up to 5 years ]
- TRM [ Time Frame: At day 100 ]
- TRM [ Time Frame: At 1 year ]
- Safety of DLI in patients with mixed or full donor chimerism as preemptive therapy to eliminate minimal residual disease [ Time Frame: Assessed up to 5 years ]
- Overall survival [ Time Frame: Assessed up to 5 years ]
- Leukemia-free survival [ Time Frame: Assessed up to 5 years ]
|Study Start Date:||July 2001|
|Estimated Primary Completion Date:||October 2018 (Final data collection date for primary outcome measure)|
Experimental: Treatment (allogeneic nonmyeloablative HSCT)
See Detailed Description
Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
Undergo nonmyeloablative allogeneic PBSC transplantationDrug: imatinib mesylate
Other Names:Drug: dasatinib
Other Names:Drug: nilotinib
Other Names:Radiation: total-body irradiation
Other Name: TBIDrug: cyclosporine
Given IV or PO
Other Names:Drug: mycophenolate mofetil
Other Names:Drug: fludarabine phosphate
Other Names:Procedure: peripheral blood stem cell transplantation
Undergo allogeneic PBSC transplantation
Other Names:Biological: therapeutic allogeneic lymphocytes
Other Name: ALLOLYMPH
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 chemotherapy.
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 doses.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00036738
|United States, Colorado|
|Presbyterian - Saint Lukes Medical Center - Health One|
|Denver, Colorado, United States, 80218|
|United States, Washington|
|VA Puget Sound Health Care System|
|Seattle, Washington, United States, 98101|
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|
|Seattle, Washington, United States, 98109|
|Principal Investigator:||George Georges||Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|