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

NCT ID: NCT05316701

Last Updated: 2025-09-26

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 187 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-21
• Study Completion Date: 2026-07-31

Brief Summary

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.

Detailed Description

Cross reference NCT04013685

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Orca-T

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).

Group Type: EXPERIMENTAL

Orca-T

Intervention Type: BIOLOGICAL

an allogeneic stem cell and T-cell immunotherapy biologic

Standard of Care alloHCT Control

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.

Group Type: ACTIVE_COMPARATOR

Standard-of-Care

Intervention Type: BIOLOGICAL

unmanipulated donor allograft

Interventions

Orca-T

an allogeneic stem cell and T-cell immunotherapy biologic

Intervention Type: BIOLOGICAL

Standard-of-Care

unmanipulated donor allograft

Intervention Type: BIOLOGICAL

Other Intervention Names

SOC

Eligibility Criteria

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

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Orca Biosystems, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

City of Hope

Duarte, California, United States

Ronald Reagan UCLA Medical Center

Los Angeles, California, United States

UC Davis

Sacramento, California, United States

Stanford Health Care

Stanford, California, United States

Colorado Blood Cancer Institute

Denver, Colorado, United States

University of Miami Hospital and Clinics - Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Moffitt Cancer Center

Tampa, Florida, United States

Winship Cancer Institute - Emory University

Atlanta, Georgia, United States

University of Chicago

Chicago, Illinois, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

University of Michigan Health System - Michigan Medicine

Ann Arbor, Michigan, United States

Weill Cornell Medicine - New York-Presbyterian Hospital

New York, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Cleveland Clinic

Cleveland, Ohio, United States

OU Health Stephenson Cancer Center

Oklahoma City, Oklahoma, United States

Oregon Health & Sciences University - Knight Cancer Institute

Portland, Oregon, United States

Vanderbilt University

Nashville, Tennessee, United States

Sarah Cannon Research Institute

Nashville, Tennessee, United States

University of Utah

Salt Lake City, Utah, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

Precision-T (PhIII component)

Identifier Type: -

Identifier Source: org_study_id