Precision-T: A Randomized Phase III Study of Orca-T in Recipients Undergoing Allogeneic Transplantation for Hematologic Malignancies

Key Inclusion Criteria:

Matched to a related or unrelated donor who is an 8/8 match for HLA-A, -B, -C, and DRB1

Diagnosed with one of the following diseases:

Acute myeloid, lymphoid 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 syndromes (MDS) that are indicated for alloHSCT per 2017 International Expert Panel recommendations and/or have therapy-related/secondary MDS, with ≤ 10% blast burden in the bone marrow

Planned to undergo MA-alloHCT including one of the following myeloablative conditioning regimens:

TBI/Cy
TBI/Etoposide
BFT
Cardiac ejection fraction at rest ≥ 45% or shortening fraction of ≥ 27% by echocardiogram or radionuclide scan (MUGA)
Diffusing capacity of the lung for carbon monoxide (DLCO) (adjusted for hemoglobin) ≥ 50%
Negative serum or urine beta-HCG test in females of childbearing potential
ALT/AST < 3 times ULN
Recipients in screening must screen negative for SARS-CoV-2 RNA using a PCR-based test
Disease Risk Index (DRI) overall risk categorization of intermediate or high
Total bilirubin ≤ upper limit of normal (ULN)
Estimated glomerular filtration rate (eGFR) ≥ 60 mL/minute

Key Exclusion Criteria:

Prior allogeneic HCT
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 anti-donor HLA antibodies against a mismatched allele in the selected donor
Karnofsky performance score < 70%
Hematopoietic cell transplantation-specific Comorbidity Index (HCT-CI) > 4
Uncontrolled bacterial, viral or fungal infections at time of enrollment
Seropositive for HIV-1 or -2, HTLV-1 or -2, Hepatitis B sAg, Hepatitis C antibody
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 malignancies or active disease within 1 year, except non-melanoma skin cancers that have been curatively resected
Psychosocial circumstances that preclude the patient being able to go through transplant or participate responsibly in follow up care
Women who are pregnant or breastfeeding
Women of childbearing potential (WOCBP) or men who have sexual contact with WOCBP unwilling to use effective forms of birth control or abstinence for one year after transplantation