Title
A Study of Engineered Donor Grafts (Orca-T) in Recipients Undergoing Allogeneic Transplantation for Hematologic Malignancies
A Multicenter Phase Ib Trial of Patients With Advanced Hematologic Malignancies Undergoing Allogeneic Hematopoietic Cell Transplantation With Orca-T (Formerly TregGraft), a T-cell-Depleted Graft With Additional Infusion of Conventional T Cells and Regulatory T Cells
Phase
Phase 1Lead Sponsor
Orca Biosystems, Inc.Study Type
InterventionalStatus
RecruitingIntervention/Treatment
treggraft ...Study Participants
255This study will evaluate the safety, tolerability, and efficacy of an engineered donor graft ("Orca-T", a T-cell-Depleted Graft With Additional Infusion of Conventional T Cells and Regulatory T Cells) in participants undergoing myeloablative allogeneic hematopoietic cell transplant transplantation for hematologic malignancies.
engineered donor allograft
This is a non-randomized, single-arm study. All enrolled subjects will receive an allogeneic HCT with the Orca-T product.
Key Inclusion Criteria: Recipients must meet all of the following criteria: Patients must diagnosed with one of the following histopathologically confirmed diseases, for which a myeloablative hematopoietic stem cell transplant (HCT) is planned: acute myeloid, lymphoid or mixed phenotype leukemia that is not in CR/CRi [Ages 18-65] myelodysplastic syndromes with > 10% to < 20% bone marrow blast burden [Ages 18-65] acute myeloid, lymphoid or mixed phenotype leukemia that is in CR/CRi but is categorized as DRI very high risk [Ages 18-65] Myelofibrosis [Ages 18-65] Blastic Plasmacytoid Dendritic Cell Neoplasm [Ages 18-65] acute myeloid, lymphoid, mixed phenotype leukemia or myelodysplastic syndromes (therapy-related/secondary MDS or eligible for alloHCT per 2017 International Expert Panel) that are in CR and intermediate to high risk per the DRI in patients aged 66 to 75 [Ages 66-75] chronic myeloid leukemia that is in chronic phase with history of blast crisis or accelerated phase and/or is resistant to or intolerant of >1 first- or second-generation TKI [Ages 18-65] 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 Key Exclusion Criteria: Recipients meeting any of the following exclusion criteria will not be eligible: 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. Pre-planned donor lymphocyte infusion (DLI) Planned pharmaceutical in vivo or ex vivo T cell depletion Positive for anti-donor HLA antibodies against an allele in the selected donor Karnofsky performance score < 70% 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 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 Concurrent malignancies or active disease within 1 year, except non-melanoma skin cancers that have been curatively resected Women who are pregnant or breastfeeding
