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

Study Overview
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Brief Summary
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This 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.

Official Title
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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

Conditions
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Acute Myeloid Leukemia, Acute Lymphoid Leukemia, Myelodysplastic Syndromes, Acute Leukemia, Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN), Chronic Myeloid Leukemia, Chronic Phase

Intervention / Treatment
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* Biological: Orca-T (formerly TregGraft)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Subjects with Acute Leukemia or Myelodysplasic Syndrome, Myelofibrosis, or BPDCN<br>This is a non-randomized, single-arm study. All enrolled subjects will receive an allogeneic HCT with the Orca-T product. | Biological: Orca-T (formerly TregGraft)<br>* engineered donor allograft<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TregGraft (Orca-T), with single agent GVHD prophylaxis |  | 365 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1-year overall survival (OS) | 1-year overall survival (OS) | 365 days | 
| 1 year graft-versus-host-disease-free and relapse-free survival (GRFS) | 1 year graft-versus-host-disease-free and relapse-free survival (GRFS) | 365 days | 
| incidence and severity of acute and chronic graft vs host disease (GvHD) | incidence and severity of acute and chronic graft vs host disease (GvHD) | 365 days | 
| incidence of serious infections | incidence of serious infections | 365 days | 
| incidence and timing of engraftment | incidence and timing of engraftment of platelets and neutrophils | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hematopoietic stem cell transplantation, acute leukemia, Myelodysplastic syndromes, matched related donor, matched unrelated donor