Induction Of Mixed Hematopoietic Chimerism Using Fludarabine, Low Dose TBI , PBSC Infusion And Post-Transplant Immunosuppression With Cyclosporine And Mycophenolate Mofetil to be Followed by Donor Lymphocyte Infusion In Patients With Chronic Myeloid Leukemia in Chronic and Accelerated Phases: A Multi-Center Study.
I. To determine if mixed hematopoietic chimerism can be safely established using a
non-myeloablative conditioning regimen in patients > 65 years of age with CML in chronic or
accelerated phase who have human leukocyte antigen (HLA) identical related donors.
II. To determine if mixed chimerism, established with non-myeloablative conditioning
regimens, can be converted to full donor hematopoietic chimerism by infusions of donor
lymphocytes (DLI), and thereby produce an immunologic cure of the malignancy.
CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) on days -4
to -2 and undergo low-dose total-body irradiation (TBI) on day 0.
TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation
(PBSCT) on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine orally (PO) twice daily (BID) or IV BID or
thrice daily (TID) on days -3 to 56 with taper to day 77 or 180, and mycophenolate mofetil
PO or IV BID on days 0-27.
DLI: At least 2 weeks after completion of immunosuppression, patients with > 5% donor
cluster of differentiation (CD)3+ T cells and no evidence of graft-versus-host disease
(GVHD) receive donor lymphocytes IV over 30 minutes. Patients may receive up to 3 DLIs at
increasing cell doses in the absence of GVHD.
After completion of study treatment, patients are followed up periodically for 5 years.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Safety of establishing mixed chimerism using this non-lethal conditioning regimen, in terms of development of GVHD, myelosuppression, infections, and treatment-related mortality
All unexpected toxicities will be summarized and reported.
Within the first 65 days
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
United States: Federal Government
|Stanford University||Stanford, California 94305|
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium||Seattle, Washington 98109|
|University of Colorado||Denver, Colorado 80217|
|Baylor University Medical Center||Dallas, Texas 75246|
|VA Puget Sound Health Care System||Seattle, Washington 98101|
|City of Hope Medical Center||Duarte, California 91010|