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.
Additional locations may be listed on ClinicalTrials.gov for NCT03670966.
Locations matching your search criteria
United States
Washington
Seattle
Fred Hutch/University of Washington/Seattle Children's Cancer ConsortiumStatus: Active
Contact: Phuong Vo
Phone: 206-667-2749
PRIMARY OBJECTIVE:
I. To estimate the maximum tolerated dose (MTD) of radiation delivered via astatine At 211 Anti-CD45 monoclonal antibody BC8-B10 (211At-BC8-B10) when combined with cyclophosphamide (CY), fludarabine (FLU) and total body irradiation (TBI) as a preparative regimen of an human leukocyte antigen (HLA)-haploidentical related donor hematopoietic cell transplantation (HCT) using post-transplantation immunosuppression with high dose CY, tacrolimus and mycophenolate mofetil (MMF) for patients aged >= 18 with advanced acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), high risk myelodysplastic syndrome (MDS), or mixed-phenotype acute leukemia (MPAL).
SECONDARY OBJECTIVES:
I. To assess disease response and duration of remission.
II. To evaluate the rates of engraftment and donor chimerism resulting from this combined preparative regimen at day +84, and to correlate level of donor chimerism with amount of 211At administered.
III. To examine rates of non-relapse mortality (NRM), immune reconstitution, incidence of grade II-IV acute and severe/moderate chronic graft-versus-host disease (GvHD).
IV. To estimate overall survival through day 100.
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.
Lead OrganizationFred Hutch/University of Washington/Seattle Children's Cancer Consortium
Principal InvestigatorPhuong Vo