Clinical Trials /

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

NCT04013685

Description:

This study will evaluate the safety, tolerability, and efficacy of an engineered donor graft ("TregGraft"/"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.

Related Conditions:
  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
  • Mixed Phenotype Acute Leukemia
  • Myelodysplastic Syndromes
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of Engineered Donor Grafts (TregGraft/Orca-T) in Recipients Undergoing Allogeneic Transplantation for Hematologic Malignancies
  • Official Title: A Multicenter Phase Ib Trial for Patients With Advanced Hematologic Malignancies Undergoing Allogeneic Hematopoietic Cell Transplantation With TregGraft (Orca-T), a T-cell-Depleted Graft With Additional Infusion of Conventional T Cells and Regulatory T Cells

Clinical Trial IDs

  • ORG STUDY ID: TRGFT-201
  • NCT ID: NCT04013685

Conditions

  • Acute Myeloid Leukemia
  • Acute Lymphoid Leukemia
  • Myelodysplastic Syndromes
  • Acute Leukemia

Interventions

DrugSynonymsArms
TregGraft (Orca-T)Subjects with Acute Leukemia or Myelodysplasic Syndrome

Purpose

This study will evaluate the safety, tolerability, and efficacy of an engineered donor graft ("TregGraft"/"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.

Trial Arms

NameTypeDescriptionInterventions
Subjects with Acute Leukemia or Myelodysplasic SyndromeExperimentalThis is a non-randomized, single-arm study. Patients will be grouped based on their underlying disease: Group 1 will enroll subjects planning to undergo myeloablative allogeneic hematopoietic cell transplantation (MA-alloHCT) for the treatment of either acute myeloid, lymphoid or mixed phenotype leukemia in complete remission (CR) or CR with incomplete hematologic recovery (CRi), and with no known minimal residual disease positivity. Group 2 will enroll subjects Subjects planning to undergo MA-alloHCT for acute myeloid, lymphoid or mixed phenotype leukemia that is either: not in morphologic CR with bone marrow infiltration by leukemic blasts of <= 10%, or in morphologic CR with evidence of minimal residual positivity by either multiparameter flow cytometric analysis or by a nucleic acid-based technique. Group 3 will enroll subjects planning to MA-alloHCT for high or very high risk myelodysplasic syndrome (MDS) myelodysplastic syndromes.
  • TregGraft (Orca-T)

Eligibility Criteria

        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

               -  high or very high risk myelodysplastic syndromes

          2. Patients with active acute leukemia (i.e. not in morphologic complete response) must
             have bone marrow infiltration by leukemic blasts of <= 10%,

          3. Patients must be matched to a related or unrelated donor

          4. Estimated glomerular filtration rate (eGFR) > 50 mL/minute

          5. Cardiac ejection fraction at rest ≥ 45% or shortening fraction of ≥ 27% by
             echocardiogram or radionuclide scan (MUGA)

          6. Diffusing capacity of the lung for carbon monoxide (DLCO) (adjusted for hemoglobin) ≥
             50%

          7. 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
      
Maximum Eligible Age:65 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:TregGraft (Orca-T), with single agent GVHD prophylaxis
Time Frame:365 days
Safety Issue:
Description:

Secondary Outcome Measures

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

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Orca Biosystems, Inc.

Trial Keywords

  • hematopoietic stem cell transplantation
  • acute leukemia
  • Myelodysplastic syndromes
  • matched related donor
  • matched unrelated donor

Last Updated

October 5, 2020