RecruitingPhase 2NCT07216443

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

A Phase 2 Trial of Orca-T Following Reduced Intensity or Nonmyeloablative Conditioning in Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome

Sponsor

Orca Biosystems, Inc.

Enrollment

80 participants

Start Date

Dec 9, 2025

Study Type

INTERVENTIONAL

Conditions

Myelodysplastic Syndromes Mixed Phenotype Acute Leukemia Leukemia, Myeloid, Acute

Summary

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).

Eligibility

Min Age: 18 Years

Inclusion Criteria15

Age ≥18 years at the time of enrollment
Diagnosed with 1 of the following diseases:
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.
Planned to undergo 1 of the following preparative regimens as per Investigator discretion:
RIC cohort: Planned RIC-alloHCT including RIC regimen with TBI/thiotepa/fludarabine
NMA cohort: Planned NMA-alloHCT including NMA regimen with fludarabine/cyclophosphamide/TBI
Identified related or unrelated donor who is an 8/8 match for HLA-A, -B, -C, and -DRB1
Estimated glomerular filtration rate ≥30 mL/minute
Cardiac ejection fraction at rest ≥40% or shortening fraction of ≥22% by echocardiogram or radionuclide scan (MUGA)
Diffusing capacity of the lung for carbon monoxide (adjusted for hemoglobin) ≥40%
Negative serum or urine β-HCG test in persons of childbearing potential
Alanine transaminase (ALT)/aspartate transaminase (AST) \<5 times the upper limit of normal (ULN)
Total bilirubin \<3 × ULN
Deemed ineligible for a fully myeloablative alloHCT per assessment of the principal investigator

Exclusion Criteria17

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
Recipient-positive antidonor HLA antibodies against a mismatched allele in the selected donor
Karnofsky performance score \<60%
For RIC cohort only: HCT-Specific Comorbidity Index (HCT-CI) ≥6
Uncontrolled bacterial, viral, or fungal infection (currently taking antimicrobial therapy and with progression or no clinical improvement) at the time of enrollment
Seropositive for HIV-1 or -2, HTLV-1 or -2, hepatitis B surface antigen, or HCV antibody unless previously treated with curative therapy and are HCV NAT negative
Known allergy or hypersensitivity to or intolerance of tacrolimus
Documented allergy or hypersensitivity to iron dextran or bovine, murine, algal, or Streptomyces avidinii proteins
Any uncontrolled autoimmune disease requiring active immunosuppressive treatment
Concurrent malignancy within 1 year except nonmelanoma skin cancer that has been curatively resected
Psychosocial circumstances that preclude the participant being able to go through transplantation or participate responsibly in follow-up care
Persons who are pregnant or breastfeeding
Person of childbearing potential (POCBP) or men who have sexual contact with POCBP who are unwilling to use effective forms of birth control or abstinence for 1 year after transplantation.
Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's or medical monitor's judgment, precludes the recipient's safe participation in and completion of the trial or which could affect compliance with the protocol or interpretation of results