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

  • Interventional
  • Recruiting
  • NCT04013685
Eligibility Details Visit Clinicaltrials.gov

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

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.

Gender
All

Age Group
18 Years to 65 Years

Accepting Healthy Volunteers?
No

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

             - Myelofibrosis

             - Blastic Plasmacytoid Dendritic Cell Neoplasm

         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

At a Glance

National Government IDNCT04013685

IRB#IRB20-0607

Lead SponsorOrca Biosystems, Inc.

Lead PhysicianSatyajit Kosuri

Collaborator(s)N/A

EligibilityAll
18 Years to 65 Years
Recruiting