A Phase I Study Combining Escalating Doses of Radiolabeled BC8 (Anti-CD45) Antibody With Fludarabine, Low-Dose TBI, PBSC Infusion and Post-Transplant Immunosuppression With Cyclosporine and Mycophenolate Mofetil to Establish Mixed or Full Donor Chimerism for Elderly Patients With Advanced Acute Myeloid Leukemia or High Risk Myelodysplastic Syndrome
I. To determine the maximum tolerated dose (MTD) of radiation delivered via 131I-BC8
antibody when combined with the non-myeloablative regimen of fludarabine, 2 Gy total-body
irradiation (TBI) + cyclosporine (CSP)/mycophenolate (MMF) in elderly patients with advanced
acute myeloid leukemia (AML) or high risk myelodysplastic syndrome (MDS).
II. To determine the rates of donor chimerism resulting from this combined preparative
regimen, and to correlate level of donor chimerism with estimated radiation doses delivered
to hematopoietic tissues via antibody.
III. To determine, within the limits of a Phase I study, disease response and duration of
IV. To assess dose-limiting toxicity (DLT) at the estimated MTD of 131I-BC8 (24 Gy) in order
to gain more confidence that the DLT rate is acceptable at this level.
OUTLINE: This is a dose-escalation study of iodine I 131 monoclonal antibody BC8.
CONDITIONING REGIMEN: Patients receive iodine I 131 monoclonal antibody BC8 intravenously
(IV) on day -12 and fludarabine phosphate IV on days -4 to -2. Patients undergo total-body
irradiation on day 0.
TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation on
IMMUNOSUPPRESSION: Patients receive cyclosporine orally or IV twice daily on days -3 to 56
with taper to day 80 (for patients with a related donor) OR days -3 to 100 with taper to day
177 (for patients with an unrelated donor) in the absence of graft-versus-host disease
(GVHD). Patients also receive mycophenolate mofetil orally or IV three times a day on days 0
to 27 (for patients with a related donor) OR on days 0 to 40 with taper to day 96 (for
patients with an unrelated donor) in the absence of GVHD.
After completion of study treatment, patients are followed up at 6, 9, and 12 months, every
6 months for 1 year, and then yearly thereafter.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of radiation delivered via 131I-BC8 antibody when combined with the nonmyeloablative regimen of fludarabine, TBI, and CSP/MMF
Through day 100 following transplant
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
United States: Food and Drug Administration
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