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.
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)
Prior alloHCT
Currently receiving corticosteroids or other immunosuppressive therapy except for approved disease-specific therapy for the patient's underlying hematologic malignancy. 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, e.g., post-transplant cyclophosphamide (Cy) or alemtuzumab
Parallel
OrcaGraft (Orca-Q)
Biological/Vaccineengineered donor allograft
6
Treatment groupsSee each treatment group below.
Dose Limiting Toxicities through Day +28 (dose escalation)
Safety and tolerability of Orca-Q (formerly OrcaGraft) in adults undergoing myeloablative allogeneic hematopoietic cell transplantation (MA-alloHCT) will be evaluated by identification of the following dose limiting toxicities: Grade ≥ 3 infusion-related reaction or cytokine release syndrome, Grade ≥ 3 acute GVHD, Any Grade ≥ 3 treatment-related non-hematologic event not clearly related to the underlying malignancy, intercurrent infection, the HCT conditioning regimen, or other pre-existing medical condition
Primary Graft failure through Day +28 (dose expansion)
Primary graft failure in the dose expansion phase, defined as being alive without recovery of neutrophils during the evaluation period
Neutrophil Engraftment through Day +28
Neutrophil engraftment defined as an absolute neutrophil count of \>/=500/mm3 for 3 consecutive days
Platelet Engraftment through Day +50
Platelet engraftment is defined as achieving a platelet count \> 20,000/mm3 for 3 consecutive days without platelet transfusion in the preceding 7 days, by Day +50
Secondary Graft Failure through Day +100
Secondary graft failure is defined as neutrophil engraftment followed by subsequent decline in absolute neutrophil counts \< 500 cells/μL, unresponsive to growth factor therapy, by Day +100
Acute GVHD through Day +100
Acute GVHD will be staged and graded per Mount Sinai Acute GvHD International Consortium (MAGIC) Standardization criteria
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