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

A 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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Acute Myeloid Leukemia; Acute Leukemia; Myelodysplastic Syndrome; Acute Lymphoid Leukemia; Therapy-Related Myelodysplastic Syndrome; Mixed Phenotype Acute Leukemia; Undifferentiated Leukemia
• Intervention / Treatment: Biological: Standard-of-Care; Biological: Orca-T

Detailed Description

Cross reference NCT04013685

• Study Type: Interventional
• Enrollment (Actual): 187
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope
    • Los Angeles, California, United States, 90095
      • Ronald Reagan UCLA Medical Center
    • Sacramento, California, United States, 95817
      • UC Davis
    • Stanford, California, United States, 94305
      • Stanford Health Care
  • Colorado
    • Denver, Colorado, United States, 80218
      • Colorado Blood Cancer Institute
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Hospital and Clinics - Sylvester Comprehensive Cancer Center
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute - Emory University
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Health System - Michigan Medicine
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10021
      • Weill Cornell Medicine - New York-Presbyterian Hospital
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • OU Health Stephenson Cancer Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Sciences University - Knight Cancer Institute
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University
    • Nashville, Tennessee, United States, 37239
      • Sarah Cannon Research Institute
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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).	Biological: Orca-T; an allogeneic stem cell and T-cell immunotherapy biologic
Active Comparator: 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.	Biological: Standard-of-Care; unmanipulated donor allograft; Other Names: SOC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-free at 12 Months for Moderate or Severe Chronic Graft-versus-Host-Disease-free Survival (cGFS) Per Endpoint Adjudication Committee (EAC)	Event-free rate estimated at 12 months for cGFS per EAC, which is defined as the time from date of allogeneic hematopoietic cell transplantation (alloHCT) (ie, day 0) to date of death from any cause or first onset of moderate or severe chronic graft-versus-host disease (cGVHD) (graded per NIH consensus criteria), whichever was earliest, within 2 years after day 0. cGVHD was assessed and graded by EAC blinded to treatment assignment. Each participant in the study is followed for up to 730 days after transplant. Primary analysis was event driven (ie, when 56 participants had died or had moderate or severe cGVHD) and was not based on duration of follow-up. The analysis was conducted using all available data at the time that the 56th event occurred, and event-free rate at 12 months was estimated regardless of length of follow-up for individual participants. At the time of analysis, not all participants have reached 730 days of follow-up because they enrolled at different times.	Day 0 through 730 days after transplantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event Rate at 12 Months for Time to Moderate or Severe cGVHD Per EAC	Event rate estimated at 12 months for time from alloHCT to first onset of moderate or severe cGVHD defined by NIH consensus criteria within 2 years after day 0. Death within 2 years after day 0 without prior moderate or severe cGVHD was considered a competing event. cGVHD was assessed and graded by an independent EAC. Each participant in the study is followed for up to 730 days after transplant. The primary analysis was triggered by the 56th cGFS event (ie, when 56 participants had died or had moderate or severe chronic GVHD) and was not based on the duration of follow-up. Therefore, the analysis was conducted using all available data at the time that the 56th cGFS event occurred, and the event rate of moderate or severe cGVHD at 12 months was estimated regardless of the length of follow-up for individual participants. At the time of analysis, not all participants have reached 730 days of follow-up because they enrolled at different times.	Day 0 through 730 days after transplantation
Event-free at 12 Months for Overall Survival (OS)	Event-free rate estimated at 12 months for OS, which is defined as time from randomization to death from any cause. Each participant in the study is followed for up to 730 days after transplant. The analysis was triggered by the 56th cGFS event (ie, when 56 participants had died or had moderate or severe chronic GVHD) and was not based on the duration of follow-up. Therefore, the analysis was conducted using all available data at the time that the 56th cGFS event occurred, and the event-free rate of OS at 12 months was estimated regardless of the length of follow-up for individual participants. At the time of analysis, not all participants have reached 730 days of follow-up because they enrolled at different times.	Up to 730 days after end of enrollment
Event-free Rate at 12 Months for Graft-versus-host Disease-free and Relapse-free Survival (GRFS) Per EAC	Event-free rate estimated at 12 months for GRFS, which is defined as time from alloHCT to death from any cause, relapse, the first onset of grade 3 or 4 acute GVHD (graded per Mount Sinai aGVHD International Consortium [MAGIC] criteria), or the first onset of moderate or severe cGVHD (graded per NIH consensus criteria), whichever is earliest, within 2 years from day 0 as assessed by independent EAC. Each participant in the study is followed for up to 730 days after transplant. The analysis was triggered by the 56th cGFS event (ie, when 56 participants had died or had moderate or severe cGVHD) and not based on duration of follow-up. Therefore, analysis was conducted using all available data at the time that the 56th cGFS event occurred, and event-free rate of GRFS at 12 months was estimated regardless of length of follow-up for individual participants. At time of analysis, not all participants have reached 730 days of follow-up because they enrolled at different times.	Day 0 through 730 days after transplantation

Collaborators and Investigators

• Sponsor: Orca Biosystems, Inc.

Publications and helpful links

General Publications

• Meyer E, Salhotra A, Gandhi A, Pantin J, Patel SS, Hoeg RT, Gomez-Arteaga A, Faramand RG, Tamari R, Waller EK, Kosuri S, Jimenez Jimenez AM, Holter-Chakrabarty J, Dholaria B, Chen YB, Hamilton BK, Magenau JM, Eghtedar A, Murray JM, Pavlova A, Fernhoff NB, McClellan JS, Killian S, Li A, Negrin RS, Oliai C. Orca-T versus allogeneic hematopoietic stem cell transplantation (PRECISION-T): a multicenter, randomized phase 3 trial. Blood. 2025 Dec 12:blood.2025031313. doi: 10.1182/blood.2025031313. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): June 21, 2022
• Primary Completion (Actual): July 15, 2024
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: March 30, 2022
• First Submitted That Met QC Criteria: March 30, 2022
• First Posted (Actual): April 7, 2022

Study Record Updates

• Last Update Posted (Actual): March 4, 2026
• Last Update Submitted That Met QC Criteria: February 18, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: hematopoietic stem cell transplantation; myelodysplastic syndrome; acute leukemia; Myelodysplastic syndromes; matched related donor; matched unrelated donor
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, Myeloid; Bone Marrow Diseases; Leukemia, Lymphoid; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes; Leukemia, Biphenotypic, Acute; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality of Health Care; Quality Indicators, Health Care; Standard of Care
• Other Study ID Numbers: Precision-T (PhIII component)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No