A Phase 1 Study of Engineered Donor Grafts (Orca-Q) in Recipients Undergoing Allogeneic Transplantation for Hematologic Malignancies

Open to people ages 18-65

1. Age ≥ 18 and ≤ 65 years at the time of enrollment
2. Diagnosed acute myeloid, lymphoid or mixed phenotype leukemia, or high or very high risk myelodysplasic syndrome (MDS) or Myelofibrosis
3. Planned to undergo myeloablative allogeneic hematopoietic stem cell transplant (HCT)
4. Matched to a 8/8 or 7/8 related or unrelated donor, or to a related haploidentical donor
5. Estimated glomerular filtration rate (eGFR) > 50 mL/minute
6. Cardiac ejection fraction at rest ≥ 45% or shortening fraction of ≥ 27% by echocardiogram or radionuclide scan (MUGA)
7. Diffusing capacity of the lung for carbon monoxide (DLCO) (adjusted for hemoglobin) ≥ 50%
8. Total bilirubin < 1.5 times upper limit of normal (ULN) (< 3 times if attributed to Gilbert's syndrome) and ALT/AST < 3 times ULN

1. Prior allogeneic HCT
2. Currently receiving corticosteroids or other immunosuppressive therapy. Topical corticosteroids or oral systemic corticosteroid doses less than or equal to 10 mg/day are allowed.
3. Planned donor lymphocyte infusion (DLI)
4. Positive anti-donor HLA antibodies against a mismatched allele in the selected donor
5. Karnofsky performance score < 70% (Appendix 12.7)
6. Hematopoietic cell transplantation-specific Comorbidity Index (HCT-CI) > 4 (Appendix 12.8)
7. Uncontrolled bacterial, viral or fungal infections (currently taking antimicrobial therapy and with progression or no clinical improvement) at time of enrollment
8. Seropositive for HIV-1 or -2, HTLV-1 or -2

9. Any uncontrolled autoimmune disease requiring active immunosuppressive treatment

   10. Concurrent malignancies or active disease within 1 year, except non-melanoma skin

   cancers that have been curatively resected

   11. History of idiopathic or secondary myelofibrosis 12. Women who are pregnant or breastfeeding