Radiolabeled BC8 (Anti-CD45) Antibody Combined With Cyclophosphamide and Total Body Irradiation Followed by HLA-matched Related or Unrelated Stem Cell Transplantation as Treatment for Advanced Acute Myeloid Leukemia and Myelodysplastic Syndrome
- Determine the efficacy, in terms of overall survival and disease-free survival, and
toxicity of cyclophosphamide and total body irradiation in patients with acute myeloid
leukemia beyond first remission receiving HLA-matched related or unrelated
hematopoietic stem cell transplantation.
- Determine the maximum tolerated dose (MTD) of iodine I 131 monoclonal antibody BC8
(I131 MOAB BC8) in these patients.
- Estimate the MTD of radiation delivered by I 131 MOAB BC8 to marrow of these patients
and assess the effects on growth of marrow stroma in vitro.
OUTLINE: This is radiation dose-escalation study. Patients are stratified according to
available donor (related vs unrelated).
Patients receive a biodistribution dose of iodine I 131 monoclonal antibody BC8 (I131 MOAB
BC8) IV, then a therapeutic dose of I131 MOAB BC8 IV 6-14 days later (day -12). Patients
undergo total body irradiation twice daily on days -6 to -4. Patients receive
cyclophosphamide IV on days -3 and -2. Bone marrow cells (or peripheral blood stem cells)
are infused on day 0.
Patients with CNS leukemic involvement receive intrathecal methotrexate twice before the
transplantation then every other week for 8 weeks beginning on day 32. These patients also
receive cranial irradiation beginning on day 32.
Cohorts of 4 patients each receive escalating doses of iodine I 131 attached to a standard
dose of monoclonal antibody BC8 until the maximum tolerated dose (MTD) is determined. The
MTD is defined as the radiation dose preceding that at which 2 of up to 6 patients
experience graft failure.
Patients are followed at 6, 9, and 12 months, every 6 months for 1 year, and then annually
PROJECTED ACCRUAL: A total of 40 patients (20 per stratum) will be accrued for this study
within 4 years.
Primary Purpose: Treatment
Eneida Nemecek, MD
Fred Hutchinson Cancer Research Center
United States: Federal Government
|Fred Hutchinson Cancer Research Center||Seattle, Washington 98109|