Hematopoietic Bone Marrow Transplantation for Patients With High-Risk Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), or Myelodysplastic Syndrome (MDS) Using Related HLA-Mismatched Donors: A Trial Using Radiolabeled Anti-CD45 Antibody Combined With Immunosuppression Before and After Transplantation
I. To determine the maximum tolerated dose of radiation delivered via 131 I-BC8 antibody
(iodine I 131monoclonal antibody BC8) when combined with pre- and post-transplant
cyclophosphamide (CY), fludarabine phosphate (FLU), 2 Gy total-body irradiation (TBI),
tacrolimus, mycophenolate mofetil (MMF), and a haploidentical allogeneic hematopoietic
marrow transplant in patients who have advanced acute myeloid leukemia (AML), acute
lymphoblastic leukemia (ALL), or high risk myelodysplastic syndromes (MDS).
II. To estimate rates of immune reconstitution, engraftment, and donor chimerism resulting
from this combined preparative regimen.
III. To determine rates of disease relapse, acute graft-versus-host disease (GvHD), and day
100 disease-free survival in patients receiving 131 I-BC8 Ab combined with CY, FLU, 2 Gy
TBI, tacrolimus, MMF, and human leukocyte antigen (HLA)-haploidentical allogeneic
hematopoietic cell transplant (HCT).
OUTLINE: This is a dose-escalation study of iodine I 131 monoclonal antibody BC8.
RADIOIMMUNOTHERAPY: Patients receive therapeutic iodine I 131 monoclonal antibody BC8 via
central line on day -14.
NONMYELOABLATIVE CONDITIONING: Patients receive FLU intravenously (IV) over 30 minutes on
days -6 to -2 and CY IV over 1 hour on days -6 and -5. Patients undergo TBI on day -1.
TRANSPLANTATION: Patients undergo allogeneic bone marrow transplantation on day 0.
POST-TRANSPLATATION IMMUNOSUPPRESSION: Patients receive CY IV over 1-2 hours on day 3, MM IV
or orally (PO) three times daily on days 4 to 35, and tacrolimus IV over 1-2 hours or PO on
days 4 to 180 with taper on day 84 .
Treatment continues in the absence of disease progression or unacceptable toxicity.
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
Maximum tolerated dose of iodine I 131 monoclonal antibody BC8
Occurrence of grade III/IV regimen related toxicities (Bearman scale)
Through day 100
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|