A Phase 1 Dose Escalation and Expansion Study of Orca-Q, an Engineered Donor Graft Derived From Mobilized Peripheral Blood, in Recipients Undergoing Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancies
This study will evaluate the safety, tolerability, and efficacy of engineered donor grafts (OrcaGraft/Orca-Q) in participants undergoing allogeneic hematopoietic cell transplant (alloHCT) transplantation for hematologic malignancies.
• Age at the time of enrollment:
‣ For MAC with fully matched donor (Arm A with 8/8 donor and Arm C) and NMA/RIC: Age ≥ 12 and ≤ 78 years
⁃ For MAC with mismatched donors (Arm A with 7/8 donor and Arm B): Age ≥ 12 and ≤ 65 years
• Diagnosed acute myeloid, lymphoblastic or mixed phenotype leukemia, or high or very high risk myelodysplastic syndrome (MDS) either in complete remission (CR) or with ≤ 10 percent of blast cells in bone marrow (BM)
• Indicated for allogeneic hematopoietic stem cell transplant (alloHCT)
• Matched to a 8/8 or 7/8 related or unrelated donor, or to a related haploidentical donor
• Estimated glomerular filtration rate (eGFR) \> 50 mL/minute (MAC with tacrolimus) or \> 30 mL/minute (NMA/RIC or MAC without tacrolimus)
• Cardiac parameters: Cardiac ejection fraction ≥ 45 percent (MAC) or ≥ 40 percent (NMA/RIC)
• Diffusing capacity of the lung for carbon monoxide (DLCO) (adjusted for hemoglobin) ≥ 50 percent for MAC or ≥ 40 percent for NMA/RIC
• Liver function: Total bilirubin \< 1.5 times upper limit of normal (ULN) (MAC) or \< 3 times ULN (NMA/RIC); alanine transaminase (ALT)/aspartate transaminase (AST) \< 3 times ULN (MAC) or \< 5 times ULN (NMA/RIC)
• Participants enrolling on NMA/RIC-alloHCT arms must be deemed unfit for a myeloablative alloHCT per assessment of the principal investigator (PI)