Clinical Trial 23814

• Overview

  Study Title:

  A Phase 2 Trial of ORCA-T Following Reduced Intensity or Nonmyeloablative Conditioning in Patients with Acute Myeloid Leukemia or Myelodysplastic Syndrome

  Summary:

  This study will evaluate the safety, tolerability, and efficacy of Orca-T in participants undergoing reduced intensity or non-myeloablative allogeneic hematopoietic cell transplantation (alloHCT) for hematologic malignancies. Orca-T is an allogeneic stem cell and T-cell immunotherapy biologic manufactured for each patient (transplant recipient) from the mobilized peripheral blood of a specific, unique donor. It is composed of purified hematopoietic stem and progenitor cells (HSPCs), purified regulatory T cells (Tregs), and conventional T cells (Tcons).

  Objective:

  Primary: RIC Cohort - To evaluate the rate of GRFS through day +365 in participants treated with RIC and Orca-T derived from an 8/8 HLA- matched related or unrelated donor followed by single‑agent tacrolimus NMA Cohort - To evaluate the rate of neutrophil engraftment by the day +28 in participants treated with NMA and Orca-T derived from an 8/8 HLA‑matched related or unrelated donor followed by single‑agent tacrolimus Secondary Objectives: To evaluate safety of Orca-T. To measure the incidence and severity of serious infections. To determine OS, NRM, RFS, GRFS, and cGFS. To measure the incidence and severity of aGVHD. To measure time of onset of aGVHD. To measure the incidence and severity of cGVHD. To measure the time of onset of cGVHD. To measure the incidence and timing of neutrophil (RIC cohort only) and platelet engraftment. To measure the incidence of steroid-refractory aGVHD and cGVHD

• Treatments

  Therapies:

  Bone Marrow Transplant; Radiotherapy

  Medications:

  ORCA-T (); Thiotepa (Thioplex); Total body irradiation (TBI) (); cyclophosphamide (); cytoxan (cyclophosphamide); fludarabine (Fludarabine phosphate)

• Inclusion Criteria

  Inclusion Criteria:
  • Age ≥18 years at the time of enrollment
  • Diagnosed with 1 of the following diseases: Acute myeloid, 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. Myelodysplastic syndrome that is indicated for alloHCT per the 2017 International Expert Panel recommendations and/or therapy-related/secondary MDS as defined by the World Health Organization (WHO) classification of myeloid malignancies, with ≤10% blast burden in the bone marrow.
  • Planned to undergo 1 of the following preparative regimens as per Investigator discretion: RIC cohort: Planned RIC-alloHCT including RIC regimen with TBI/thiotepa/fludarabine NMA cohort: Planned NMA-alloHCT including NMA regimen with fludarabine/cyclophosphamide/TBI
  • Identified related or unrelated donor who is an 8/8 match for HLA-A, -B, -C, and -DRB1
  • Estimated glomerular filtration rate ≥30 mL/minute
  • Cardiac ejection fraction at rest ≥40% or shortening fraction of ≥22% by echocardiogram or radionuclide scan (MUGA)
  • Diffusing capacity of the lung for carbon monoxide (adjusted for hemoglobin) ≥40%
  • Negative serum or urine β-HCG test in persons of childbearing potential
  • Alanine transaminase (ALT)/aspartate transaminase (AST) > Total bilirubin > Deemed ineligible for a fully myeloablative alloHCT per assessment of the principal investigator

• Exclusion Criteria

  Exclusion Criteria:
  • Prior alloHCT
  • Currently receiving corticosteroids or other immunosuppressive therapy. Topical corticosteroids or oral systemic corticosteroid doses less than or equal to 10 mg/day are allowed.
  • Planned donor lymphocyte infusion (DLI)
  • Planned pharmaceutical in vivo or ex vivo T-cell depletion
  • Recipient-positive antidonor HLA antibodies against a mismatched allele in the selected donor
  • Karnofsky performance score > For RIC cohort only: HCT-Specific Comorbidity Index (HCT-CI) ≥6
  • Uncontrolled bacterial, viral, or fungal infection (currently taking antimicrobial therapy and with progression or no clinical improvement) at the time of enrollment
  • Seropositive for HIV-1 or -2, HTLV-1 or -2, hepatitis B surface antigen, or HCV antibody unless previously treated with curative therapy and are HCV NAT negative
  • 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 malignancy within 1 year except nonmelanoma skin cancer that has been curatively resected
  • Psychosocial circumstances that preclude the participant being able to go through transplantation or participate responsibly in follow-up care
  • Persons who are pregnant or breastfeeding
  • Person of childbearing potential (POCBP) or men who have sexual contact with POCBP who are unwilling to use effective forms of birth control or abstinence for 1 year after transplantation.
  • Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's or medical monitor's judgment, precludes the recipient's safe participation in and completion of the trial or which could affect compliance with the protocol or interpretation of results

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