A Study Evaluating Escalating Doses of 211^At-Labeled Anti-CD45 MAb BC8-B10 (211^At-BC8-B10) Followed by Allogeneic Hematopoietic Cell Transplantation for High-Risk Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), or Myelodysplastic Syndrome (MDS)
Summary
This phase I/II trial studies the side effects and best dose of 211\^astatine(At)-BC8-B10 before donor stem cell transplant in treating patients with high-risk acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or mixed-phenotype acute leukemia. Radioactive substances, such as astatine-211, linked to monoclonal antibodies, such as BC8, can bind to cancer cells and give off radiation which may help kill cancer cells and have less of an effect on healthy cells before donor stem cell transplant.
Detailed description
OUTLINE: This is a dose-escalation study of 211\^At-BC8-B10. Patients receive 211\^At-BC8-B10 intravenously (IV) over 6-8 hours on day -7 and may receive 131\^I-BC8-B10 IV on day -7 and fludarabine phosphate IV over 30 minutes on days -4, -3 and -2. Patients undergo TBI and peripheral blood stem cell (PBSC) transplant on day 0. Patients also receive cyclosporine orally (PO) or IV every 12 hours on days -3 to 56 and then tapered to day 180 (for patients with related donors), or continuing to day 96 and then tapered to day 150 (for patients with unrelated donors). Patients receive mycophenolate mofetil PO or IV (first dose to occur 4-6 hours after PBSC infusion) every 12 hours on days 0-27 (for patients with related donors) or every 8 hours on day 0 and then reduced to every 12 hours on days 30-150 then tapered to day 180 (for patients with unrelated donors). Patients may undergo single photon emission computed tomography (SPECT), bone marrow aspirate sample and blood sample collection on study. After completion of study treatment, patients are followed up at 100 days and then at 6, 9, 12, 18 and 24 months.
Arms & interventions
- DrugCyclosporine
Given PO or IV
- DrugFludarabine Phosphate
Given IV
- DrugMycophenolate Mofetil
Given PO or IV
- ProcedurePeripheral Blood Stem Cell Transplantation
Undergo allogeneic PBSC transplant
- RadiationPretargeted Radioimmunotherapy
Given 211\^At-BC8-B10 IV
- RadiationTotal-Body Irradiation
Undergo TBI
- RadiationPretargeted Radioimmunotherapy
Given 131\^I-BC8-B10 IV
- ProcedureBiospecimen Collection
Undergo blood and bone marrow aspirate sample collection
- ProcedureSingle Photon Emission Computed Tomography
Undergo SPECT
Outcome measures
Primary
Incidence of grades III/IV Bearman regimen-related toxicity
The maximum tolerated dose will be defined as the dose of 211\^At-BC8-B10 used in combination with the reduced-intensity hematopoietic cell transplantation conditioning regimen that is associated with a grade III/IV regimen-related toxicity or true dose limiting toxicity rate of 25%.the data, thereby generating a dose-response curve based on the observed toxicity rate at the various dose levels visited. Based on this fitted model, the maximum tolerated dose is estimated to be the dose that is associated with a toxicity rate of 25%.
Time frame: Up to 100 days following hematopoietic cell transplantation
Secondary
Engraftment
Time frame: Up to day 100
Chimerism
Time frame: Up to day 84
Non-relapse mortality
Time frame: Up to 2 years
Acute graft versus host disease
Time frame: Up to day 180
Achievement of remission
Time frame: Up to 2 years
Duration of remission
Time frame: Up to 2 years
Overall survival
Time frame: Up to 100 days
Disease-free survival
Time frame: Up to 100 days
Eligibility criteria
Study locations (1)
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109
References
- Li Y, Hamlin DK, Chyan MK, Wong R, Dorman EF, Emery RC, Woodle DR, Manger RL, Nartea M, Kenoyer AL, Orozco JJ, Green DJ, Press OW, Storb R, Sandmaier BM, Wilbur DS. cGMP production of astatine-211-labeled anti-CD45 antibodies for use in allogeneic hematopoietic cell transplantation for treatment of advanced hematopoietic malignancies. PLoS One. 2018 Oct 18;13(10):e0205135. doi: 10.1371/journal.pone.0205135. eCollection 2018.(PubMed)