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).
Age ≥18 years at the time of enrollment
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.
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.
RIC cohort: Planned RIC-alloHCT including RIC regimen with TBI/thiotepa/fludarabine
Prior alloHCT
Currently receiving corticosteroids or other immunosuppressive therapy. Topical corticosteroids or oral systemic corticosteroid doses less than or equal to 10 mg/day are allowed.
Planned donor lymphocyte infusion (DLI)
Planned pharmaceutical in vivo or ex vivo T-cell depletion
Single group
Orca-T
Biological/VaccineAn allogeneic stem cell and T-cell immunotherapy biologic
RIC Cohort: GVHD-free and relapse-free survival (GRFS)
GRFS is defined as the time from the date of transplantation to the date of death from any cause, relapse, the first onset of grade 3 or 4 acute GVHD (graded per MAGIC criteria), or the first onset of moderate or severe chronic GVHD (graded per NIH consensus criteria), whichever is earliest.
NMA Cohort: Incidence of neutrophil engraftment
Incidence of neutrophil engraftment is defined as achieving an ANC ≥500/mm3 for 3 consecutive days by day +28. The first of the 3 days will be designated the day of engraftment. If the ANC never drops below 500/mm3, day +1 will be designated the day of engraftment.
NMA Cohort: Time to neutrophil engraftment
The first of the 3 days will be designated the day of engraftment. If the ANC never drops below 500/mm3, day +1 will be designated the day of engraftment.
Safety of Orca-T
The incidence of graft failure, grade ≥3 acute GVHD (per MAGIC criteria), grade ≥4 infection (per CTCAE v5.0), manufacturing failure, and non-relapse mortality for each cohort.
Incidence of serious infections
The incidence of grade ≥3 infection (per CTCAE v5.0)
Severity of serious infection
The severity of grade ≥3 infection (per CTCAE v5.0)
Overall survival
The rate of overall survival for each cohort.
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