Precision-T: A Randomized Study of Orca-T in Recipients Undergoing Allogeneic Transplantation for Hematologic Malignancies

Orca Bio

Status and phase: Active, not recruiting; Phase 3

Conditions: Acute Leukemia; Therapy-Related Myelodysplastic Syndrome; Mixed Phenotype Acute Leukemia; Acute Lymphoid Leukemia; Myelodysplastic Syndrome; Undifferentiated Leukemia; Acute Myeloid Leukemia

Treatments: Biological: Orca-T; Biological: Standard-of-Care

Study type: Interventional

Funder types: Industry

Identifiers

NCT05316701

Precision-T (PhIII component)

Details and patient eligibility

About

This study will evaluate the safety, tolerability, and efficacy of Orca-T, 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) in participants undergoing myeloablative allogeneic hematopoietic cell transplant transplantation for hematologic malignancies.

This posting represents the Phase III component of Precision-T. The Precision-T Ph1b component is described under NCT04013685.

Full description

Cross reference NCT04013685

Enrollment: 187 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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
  • Myelodysplastic syndromes (MDS) that are indicated for alloHSCT per 2017 International Expert Panel recommendations and/or have therapy-related/secondary MDS, with ≤ 10% blast burden in the bone marrow

• 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 < 3 times ULN

• 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

Key Exclusion Criteria:

• 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.
• 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 < 70%
• 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, HTLV-1 or -2, Hepatitis B sAg, 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
• Psychosocial circumstances that preclude the patient being able to go through transplant or participate responsibly in follow up care
• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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187 participants in 2 patient groups

Orca-T

Experimental group

Description:

For patients randomized to the Orca-T arm, Orca-T will be administered after myeloablative conditioning regimen. Single-agent GVHD prophylaxis with tacrolimus will be administered following Tcon infusion (generally Day +3).

Treatment:

Biological: Orca-T

Standard of Care alloHCT Control

Active Comparator group

Description:

For patients randomized to the standard-of-care control arm, an unmanipulated allograft derived from the peripheral blood of a matched donor will be administered after a myeloablative conditioning regimen. Dual-agent prophylaxis consisting of tacrolimus plus methotrexate will be administered starting on Day -3.

Treatment:

Biological: Standard-of-Care