Trial of Orca-T Following Reduced Intensity or Nonmyeloablative Conditioning in Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome

This study will evaluate the safety, tolerability, and efficacy of Orca-T in participants undergoing reduced intensity or non-myeloablative allogeneic hematopoietic cell transplantation (alloHCT) for hematologic malignancies. Orca-T is an allogeneic stem cell and T-cell immunotherapy biologic manufactured for each patient (transplant recipient) from the mobilized peripheral blood of a specific, unique donor. It is composed of purified hematopoietic stem and progenitor cells (HSPCs), purified regulatory T cells (Tregs), and conventional T cells (Tcons).

Inclusion Criteria: 1. Age ≥18 years at the time of enrollment 2. Diagnosed with 1 of the following diseases: 1. Acute myeloid, or mixed phenotype leukemia in complete remission (CR) or CR with incomplete hematologic recovery (CRi), with or without the presence of known minimal residual disease. 2. Myelodysplastic syndrome that is indicated for alloHCT per the 2017 International Expert Panel recommendations and/or therapy-related/secondary MDS as defined by the World Health Organization (WHO) classification of myeloid malignancies, with ≤10% blast burden in the bone marrow. 3. Planned to undergo 1 of the following preparative regimens as per Investigator discretion: 1. RIC cohort: Planned RIC-alloHCT including RIC regimen with TBI/thiotepa/fludarabine 2. NMA cohort: Planned NMA-alloHCT including NMA regimen with fludarabine/cyclophosphamide/TBI 4. Identified related or unrelated donor who is an 8/8 match for HLA-A, -B, -C, and -DRB1 5. Estimated glomerular filtration rate ≥30 mL/minute 6. Cardiac ejection fraction at rest ≥40% or shortening fraction of ≥22% by echocardiogram or radionuclide scan (MUGA) 7. Diffusing capacity of the lung for carbon monoxide (adjusted for hemoglobin) ≥40% 8. Negative serum or urine β-HCG test in persons of childbearing potential 9. Alanine transaminase (ALT)/aspartate transaminase (AST) \