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Clinical Trial 20877

Cancer Type: Malignant Hematology
Study Type: Treatment
NCT#: NCT04013685

Phase: Phase I
Principal Investigator: Faramand, Rawan

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Overview

Study Title

A Phase Ib /Randomized Phase III Trial of Patients with Advanced Hematologic Malignancies Undergoing Allogeneic Hematopoietic Cell Transplantation with Either Orca-T, a T-cell-Depleted Graft with Additional Infusion of Conventional T cells and Regulatory T cells, or Standard-of-Care Allogeneic Graft

Summary

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.

Objective

Primary: To characterize the safety of administration of conventional T cells (Tcon) and regulatory T cells (Treg) in patients undergoing allogeneic hematopoietic cell transplantation (HCT) with HLA matched donors (related or unrelated) using a T cell depleted graft [CD34+ hematopoietic stem and progenitor cells ( CD34+ HSPC )], collectively referred to as TregGraft, with single agent GVHD prophylaxis. Secondary: To determine the 1-year overall survival (OS), and graft-versus-host-disease-free and relapse-free survival (GRFS) in patients undergoing allogeneic HCT with matched donors; To measure the incidence and severity of acute and chronic graft vs host disease (GvHD); To measure incidence of serious infections; To measure incidence and timing of engraftment

Treatments

Therapies

Therapy (NOS)

Medications

FK506 (Tacrolimus); Rapamune (Sirolimus); Rapamycin (Sirolimus); Sirolimus (); Tacrolimus ()

Inclusion Criteria

Key Inclusion Criteria:

  • Matched to a related or unrelated donor who is an 8/8 match for HLA-A, -B, -C, and DRB1
  • Diagnosed with one of the following diseases: Acute myeloid, lymphoid or mixed phenotype leukemia in complete remission (CR) or CR with incomplete hematologic recovery (CRi), with or without the presence of known minimal residual disease, OR Myelodysplastic syndromes (MDS) that are high to very high risk or therapy-related/secondary MDS
  • Planned to undergo MA-alloHCT including one of the following myeloablative conditioning regimens: TBI/Cy, TBI/Etoposide, BFT
  • 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%
  • Negative serum or urine beta-HCG test in females of childbearing potential
  • ALT/AST > Recipients in screening must screen negative for SARS-CoV-2 RNA using a PCR-based test
  • Disease Risk Index (DRI) overall risk categorization of intermediate or high
  • Total bilirubin ≤ upper limit of normal (ULN)
  • Estimated glomerular filtration rate (eGFR) ≥ 60 mL/minute

  • Exclusion Criteria

    Key Exclusion Criteria:

  • 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
  • Recipient positive anti-donor HLA antibodies against a mismatched allele in the selected donor
  • Karnofsky performance score > Hematopoietic cell transplantation-specific Comorbidity Index (HCT-CI) > 4
  • Uncontrolled bacterial, viral or fungal infections at time of enrollment
  • Seropositive for HIV-1 or -2 antibody, HTLV-1 or -2 antibody, Hepatitis B sAg, or Hepatitis C antibody
  • Known allergy or hypersensitivity to, or intolerance of, tacrolimus
  • Documented allergy or hypersensitivity to iron dextran or bovine, murine, algal or Streptomyces avidinii proteins
  • 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
  • Women of childbearing potential (WOCBP) or men who have sexual contact with WOCBP unwilling to use effective forms of birth control or abstinence for one year after transplantation
  • Other exclusions apply

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