A Phase 1 Study of Orca-Q in Recipients Undergoing Allogeneic Transplantation for Hematologic Malignancies

Eligibility Criteria

• 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), myelofibrosis, or chronic myeloid leukemia
• 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