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

Overview

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.

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: April 30, 2024

Interventions

  • Biological: Orca-T (formerly TregGraft)
    • engineered donor allograft

Arms, Groups and Cohorts

  • Experimental: Subjects with Acute Leukemia or Myelodysplasic Syndrome, Myelofibrosis, or BPDCN
    • This is a non-randomized, single-arm study. All enrolled subjects will receive an allogeneic HCT with the Orca-T product.

Clinical Trial Outcome Measures

Primary Measures

  • TregGraft (Orca-T), with single agent GVHD prophylaxis
    • Time Frame: 365 days

Secondary Measures

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

Participating in This Clinical Trial

Key Inclusion Criteria:

Recipients must meet all of the following criteria: 1. 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] 2. Patients must be matched to a 8/8 HLA-matched related or unrelated donor 3. Estimated glomerular filtration rate (eGFR) > 50 mL/minute 4. Cardiac ejection fraction at rest ≥ 45% or shortening fraction of ≥ 27% by echocardiogram or radionuclide scan (MUGA) 5. Diffusing capacity of the lung for carbon monoxide (DLCO) (adjusted for hemoglobin) ≥ 50% 6. 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: 1. History of 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. Pre-planned donor lymphocyte infusion (DLI) 4. Planned pharmaceutical in vivo or ex vivo T cell depletion 5. Positive for anti-donor HLA antibodies against an allele in the selected donor 6. Karnofsky performance score < 70% 7. Hematopoietic cell transplantation-specific Comorbidity Index (HCT-CI) > 4 8. Uncontrolled bacterial, viral or fungal infections (currently taking antimicrobial therapy and with progression or no clinical improvement) at time of enrollment 9. Seropositive for HIV-1 or -2 antibody, HTLV-1 or -2 antibody, Hepatitis B sAg, or Hepatitis C antibody 10. Any uncontrolled autoimmune disease requiring active immunosuppressive treatment 11. Concurrent malignancies or active disease within 1 year, except non-melanoma skin cancers that have been curatively resected 12. Women who are pregnant or breastfeeding

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 75 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Orca Biosystems, Inc.
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Contact(s)
    • James S McClellan, MD PhD, 530-414-9743, info@orcabiosystems.com

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