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

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