A Phase II Trial Combining Radiolabeled BC8 (Anti-CD45) Antibody With Fludarabine and Low Dose TBI Followed by Related or Unrelated PBSC Infusion and Post-Transplant Immunosuppression for Patients With Advanced AML or High Risk Myelodysplastic Syndrome
I. To evaluate the maximum tolerated dose (MTD) and the transplant-related mortality (TRM)
and toxicity of delivering 131I-BC8 (iodine I 131 monoclonal antibody BC8) (anti-CD45
antibody) at a starting dose of 22 Gy to the normal organ receiving the highest dose in
combination with the non-myeloablative regimen of fludarabine (fludarabine phosphate) (FLU),
2 Gy total body irradiation (TBI), cyclosporine (CSP), mycophenolate mofetil (MMF), and
human leukocyte antigen (HLA)-matched related or unrelated allogeneic hematopoietic stem
cell transplant (HSCT) in patients 16 to 50 years old who have advanced acute myeloid
leukemia (AML) or high risk myelodysplastic syndrome (MDS).
II. To estimate 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 rates of disease relapse, graft vs. host disease, and 2-year disease-free
survival in patients receiving 131I-BC8 antibody combined with FLU, 2 Gy TBI, CSP, MMF, and
HLA-matched related or unrelated allogeneic HSCT.
OUTLINE: This is a dose-escalation study of iodine I 131 monoclonal antibody BC8.
RADIOIMMUNOTHERAPY: Patients receive therapeutic iodine I 131 monoclonal antibody BC8
intravenously (IV) on day -12.
CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo total
body irradiation (TBI) on day 0.
TRANSPLANTATION: After completion of TBI, patients undergo allogeneic peripheral blood stem
cell (PBSC) transplant on day 0.
IMMUNOSUPPRESSION: Patients with a matched related donor receive cyclosporine IV or orally
(PO) twice daily on days -3 to 56 followed by a taper to day 180 in the absence of
graft-versus-host disease. Beginning 4-6 hours after PBSC transplant, these patients also
receive mycophenolate mofetil PO 2 times daily on days 0 to 27. Patients with a matched
unrelated donor receive cyclosporine IV or PO twice daily on days -3 to 100 followed by a
taper to day 180. Beginning 4-6 hours after PBSC transplant, these patients also receive
mycophenolate mofetil PO 3 times daily on days 0 to 40 followed by a taper to day 96.
After completion of study treatment, patients are followed up at 6, 9, 12, 18, and 24 months
and then annually thereafter.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Incidence of dose-limiting toxicities to determine MTD of radiation delivered to normal organ by iodine I 131 monoclonal antibody BC8
Escalation by 2 Gy increments will occur until a patient experiences a Grade III/IV regimen-related toxicity (Bearman) or dose-limiting toxicity (DLT), at which point the second stage will begin at the next lower dose level. Estimated to be the dose that is associated with a toxicity rate of 25%.
Up to 100 days post transplant
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
United States: Food and Drug Administration
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium||Seattle, Washington 98109|