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

Prior treatment

• History of 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.
• Positive for anti-donor HLA antibodies against an allele in the selected donor
• Hematopoietic cell transplantation-specific Comorbidity Index (HCT-CI) \>4
• Uncontrolled bacterial, viral or fungal infections (currently taking antimicrobial therapy and with progression or no clinical improvement) at time of enrollment
• Concurrent malignancies or active disease within 1 year, except non-melanoma skin cancers that have been curatively resected

Other illness

• Seropositive for HIV-1 or -2 antibody, HTLV-1 or -2 antibody, Hepatitis B sAg, or Hepatitis C antibody
• Any uncontrolled autoimmune disease requiring active immunosuppressive treatment

Lab values

• Pre-planned donor lymphocyte infusion (DLI)

Other

• Recipients meeting any of the following exclusion criteria will not be eligible:
• Planned pharmaceutical in vivo or ex vivo T cell depletion
• Karnofsky performance score \<70%
• Women who are pregnant or breastfeeding

• Recipients must meet all of the following criteria:
• Patients must be diagnosed with 1 of the following histopathologically confirmed diseases, for which a myeloablative hematopoietic stem cell transplant (HCT) is planned:
  • Acute myeloid, lymphoid, or mixed phenotype/undifferentiated leukemia who are not in CR or CRi (active disease) and/or MDS with \>10% to \<20% bone marrow blast burden (ages 18 to 75 years)
  • Acute leukemia in CR/CRi or MDS that is DRI intermediate to high risk (ages 66 to 75 years)
  • BPDCN (ages 18 to 65 years)
  • Participants aged 18 to 65 who would be eligible for the Phase 3 component of Precision-T except for mild impairments of renal and/or hepatic function as defined by an eGFR of 50 to \<60 mL/min and/or a total bilirubin of \>ULN to ≤2 x ULN and diagnosed with either of the following:
  • Acute myeloid, lymphoid, or mixed phenotype/undifferentiated leukemia that is in CR/CRi and DRI intermediate to high risk
  • MDS that is DRI intermediate to high risk
  • Acute or chronic leukemia in remission that is DRI low risk (ages 18 to 65 years), including the following:
  • CML in chronic phase but with a history of accelerated phase or blast crisis or who are resistant to or intolerant of more than 1 first- and second-generation tyrosine kinase inhibitors
  • Acute myeloid leukemia (AML) with inv(16) without accompanying complex cytogenetics
• Patients must be matched to a 8/8 HLA-matched related or unrelated donor
• Estimated glomerular filtration rate (eGFR) \>50 mL/minute
• 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%
• Total bilirubin \<2 times upper limit of normal (ULN) (patients with Gilbert's syndrome may be included where hemolysis has been excluded) and ALT/AST \<3 times ULN