This phase I/II trial studies the side effects and best dose of a radioactive agent linked to an antibody (211At-BC8-B10) followed by donor stem cell transplant in treating patients with high-risk acute leukemia or myelodysplastic syndrome that has come back (recurrent) or isn't responding to treatment (refractory). 211At-BC8-B10 is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Giving chemotherapy and total body irradiation before a stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the patient, they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can attack the body's normal cells, called graft versus host disease. Giving cyclophosphamide, mycophenolate mofetil, and tacrolimus after a transplant may stop this from happening.
OUTLINE: This is a dose-escalation study of astatine At 211 anti-CD45 monoclonal antibody BC8-B10. PREPARATIVE REGIMEN: Patients receive astatine At 211 anti-CD45 monoclonal antibody BC8-B10 infusion over 6-8 hours on day -8, fludarabine intravenously (IV) over 30 minutes on days -6 to -2, and cyclophosphamide IV over 1 hour on days -6 and -5. Patients also undergo TBI on day -1. TRANSPLANT: Patients undergo peripheral blood stem cell (PBSC) or bone marrow transplant on day 0. GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV over 1-2 hours on days 3-4, mycophenolate mofetil IV or PO three times daily (TID) on days 5-35, and tacrolimus IV over 1-2 hours (changed to PO once tolerated) on days 5-180 with taper beginning on day 84 per physician discretion. Patients also begin granulocyte colony-stimulating factor (G-CSF) IV or subcutaneously (SC) on day 5 to continue until absolute neutrophil count (ANC) \> 1000/mm\^3 x 3 days. Patients undergo bone marrow biopsy and aspiration and blood sample collection throughout the study. After completion of study treatment, patients are followed up at day 100, and at 6, 9, 12, 18, and 24 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Given via infusion
Given IV
Undergo TBI
Undergo PBSC transplantation
Undergo bone marrow transplant
Given IV or PO
Given IV or SC
Given IV
Given IV or PO
Undergo bone marrow biopsy and aspiration
Undergo blood sample collection
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
RECRUITINGToxicity: Proportion of patients who develop grades III/IV Bearman regimen-related toxicity
Proportion of patients who develop grades III/IV Bearman regimen-related toxicity.
Time frame: Up 100 days after hematopoietic cell transplantation (HCT)
Achievement of remission
Time frame: Up to 2 years
Rate of engraftment
Time frame: Up to 2 years
Donor chimerism
Time frame: At days 28, 56, 84, 180, and at 1 year
Non-relapse mortality (NRM)
Time frame: Up to 2 years
Number of patients experiencing Immune reconstitution
Time frame: Up to 2 years
Number of patients experiencing Number of Grade II-IV acute graft versus host disease (GVHD)
Time frame: Up to 2 years
Number of patients experiencing Moderate/severe chronic GVHD
Time frame: Up to 2 years
Overall survival
Time frame: Up to 100 days
Disease-free survival
Time frame: Up to day 100
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