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Active, not recruitingNCT05316701Orca-TUpdated Mar 4, 2026Results posted

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

A Phase 3 interventional study of Orca-T and Standard-of-Care in Acute Myeloid Leukemia, Acute Lymphoid Leukemia and Mixed Phenotype Acute Leukemia, sponsored by Orca Biosystems, Inc.. Active, not recruiting at 19 sites in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2026-03-04.

Sponsored by Orca Biosystems, Inc. · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
187
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study 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.

Read the detailed description

Cross reference NCT04013685

02

Conditions studied

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

Keywords

  • hematopoietic stem cell transplantation
  • acute leukemia
  • Myelodysplastic syndromes
  • matched related donor
  • matched unrelated donor
  • myelodysplastic syndrome
03

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility 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
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
187 participants (actual)

Study arms

  • 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

  • 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

Interventions

  • BiologicalOrca-T

    an allogeneic stem cell and T-cell immunotherapy biologic

  • BiologicalStandard-of-Care

    unmanipulated donor allograft

    Also known as: SOC

05

What researchers measure

Primary outcomes

  1. 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.

    Time frame: Day 0 through 730 days after transplantation

Secondary outcomes

  1. 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.

    Time frame: Day 0 through 730 days after transplantation

  2. 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.

    Time frame: Up to 730 days after end of enrollment

  3. 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.

    Time frame: Day 0 through 730 days after transplantation

06

Results

Posted Sep 26, 2025

Participant flow

187 participants were randomized to treatment from 19 study centers, of which 182 participants were treated

Participant flow — Overall Study
MilestoneOrca-TStandard of Care
Started9394
Participants treated8894
Completed02
Not completed9392
Withdrew: Adverse event01
Withdrew: Death39
Withdrew: Lost to follow-up10
Withdrew: Physician decision14
Withdrew: Withdrawal by subject35
Withdrew: Progression/relapse149
Withdrew: Received standard of care10
Withdrew: Ongoing7064

Outcome measures

PrimaryEvent-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.

Time frame:
Day 0 through 730 days after transplantation
Reported as:
Number · Percentage of participants
Event-free at 12 Months for Moderate or Severe Chronic Graft-versus-Host-Disease-free Survival (cGFS) Per Endpoint Adjudication Committee (EAC)
Percentage of participantsOrca-TStandard of Care
Event-free at 12 Months for Moderate or Severe Chronic Graft-versus-Host-Disease-free Survival (cGFS) Per Endpoint Adjudication Committee (EAC)78.0 (65.0 to 86.6)38.4 (26.2 to 50.5)
Statistical analysis
  • Orca-T vs Standard of Care · Log Rank · p = <0.00001 · Hazard ratio (hr): 0.26 · 95% CI 0.14 to 0.47
SecondaryEvent 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.

Time frame:
Day 0 through 730 days after transplantation
Reported as:
Number · Percentage of participants
Event Rate at 12 Months for Time to Moderate or Severe cGVHD Per EAC
Percentage of participantsOrca-TStandard of Care
Event Rate at 12 Months for Time to Moderate or Severe cGVHD Per EAC12.6 (5.3 to 23.1)44.0 (31.3 to 56.1)
Statistical analysis
  • Orca-T vs Standard of Care · Gray's test · p = 0.00002 · Hazard ratio (hr): 0.19 · 95% CI 0.08 to 0.43
SecondaryEvent-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.

Time frame:
Up to 730 days after end of enrollment
Reported as:
Number · Percentage of participants
Event-free at 12 Months for Overall Survival (OS)
Percentage of participantsOrca-TStandard of Care
Event-free at 12 Months for Overall Survival (OS)93.9 (85.8 to 97.4)83.1 (72.9 to 89.8)
Statistical analysis
  • Orca-T vs Standard of Care · Log Rank · p = 0.11823 · Hazard ratio (hr): 0.49 · 95% CI 0.20 to 1.22
SecondaryEvent-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.

Time frame:
Day 0 through 730 days after transplantation
Reported as:
Number · Percentage of participants
Event-free Rate at 12 Months for Graft-versus-host Disease-free and Relapse-free Survival (GRFS) Per EAC
Percentage of participantsOrca-TStandard of Care
Event-free Rate at 12 Months for Graft-versus-host Disease-free and Relapse-free Survival (GRFS) Per EAC63.1 (50.0 to 73.6)30.9 (20.0 to 42.4)
Statistical analysis
  • Orca-T vs Standard of Care · Log Rank · p = 0.00003 · Hazard ratio (hr): 0.37 · 95% CI 0.23 to 0.60

Adverse events

Collected over A treatment-emergent AE (TEAE) was any AE that started on or after alloHCT infusion (Orca-T or SoC) through study completion (day +730).. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Orca-T3/88 (3.4%)34/88 (38.6%)88/88 (100%)
Standard of Care9/94 (9.6%)53/94 (56.4%)94/94 (100%)
Most frequent serious events
Showing 10 of 112
Most frequent serious events
EventOrca-TStandard of Care
Acute graft-versus-host diseaseImmune system disorders6/8812/94
SepsisInfections and infestations7/886/94
PneumoniaInfections and infestations1/886/94
Chronic graft-versus-host diseaseImmune system disorders1/886/94
PyrexiaGeneral disorders5/881/94
COVID-19Infections and infestations0/885/94
Bacterial sepsisInfections and infestations4/884/94
Acute kidney injuryRenal and urinary disorders2/884/94
Venoocclusive liver diseaseHepatobiliary disorders3/881/94
Septic shockInfections and infestations1/883/94
Most frequent other events
Showing 10 of 114
Most frequent other events
EventOrca-TStandard of Care
NauseaGastrointestinal disorders79/8879/94
DiarrhoeaGastrointestinal disorders71/8883/94
FatigueGeneral disorders50/8848/94
HypomagnesaemiaMetabolism and nutrition disorders49/8853/94
StomatitisGastrointestinal disorders32/8850/94
ThrombocytopeniaBlood and lymphatic system disorders46/8844/94
Decreased appetiteMetabolism and nutrition disorders40/8847/94
VomitingGastrointestinal disorders43/8843/94
Febrile neutropeniaBlood and lymphatic system disorders32/8842/94
Chronic graft-versus-host diseaseImmune system disorders13/8840/94

Baseline characteristics

Intent-to-Treat (ITT): All enrolled participants who were randomized to either Orca-T or standard of care (SoC), regardless of whether they received Orca-T/SoC or not; participants were analyzed according to their randomized treatment assignment

Age, Categorical
Age, Categorical(Participants)Orca-TStandard of CareTotal
<=18 years000
Between 18 and 65 years9394187
>=65 years000
Sex: Female, Male
Sex: Female, Male(Participants)Orca-TStandard of CareTotal
Female404484
Male5350103
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Orca-TStandard of CareTotal
Hispanic or Latino262450
Not Hispanic or Latino6259121
Unknown or Not Reported51116
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Orca-TStandard of CareTotal
American Indian or Alaska Native123
Asian10818
Native Hawaiian or Other Pacific Islander112
Black or African American123
White7663139
More than one race000
Unknown or Not Reported41822
Region of Enrollment
Region of Enrollment(participants)Orca-TStandard of CareTotal
United States9394187
Primary Disease
Primary Disease(Participants)Orca-TStandard of CareTotal
Acute Lymphoid Leukemia (ALL)302757
Acute Myeloid Leukemia (AML)4951100
High-risk Myelodysplastic Syndrome (MDS)121123
Mixed Phenotype Acute Leukemia (MPAL)257
07

Study locations

19 sites
  • City of Hope
    Duarte, California 91010, United States
  • Ronald Reagan UCLA Medical Center
    Los Angeles, California 90095, United States
  • UC Davis
    Sacramento, California 95817, United States
  • Stanford Health Care
    Stanford, California 94305, United States
  • Colorado Blood Cancer Institute
    Denver, Colorado 80218, United States
  • University of Miami Hospital and Clinics - Sylvester Comprehensive Cancer Center
    Miami, Florida 33136, United States
  • Moffitt Cancer Center
    Tampa, Florida 33612, United States
  • Winship Cancer Institute - Emory University
    Atlanta, Georgia 30322, United States
  • University of Chicago
    Chicago, Illinois 60637, United States
  • Massachusetts General Hospital
    Boston, Massachusetts 02114, United States
  • University of Michigan Health System - Michigan Medicine
    Ann Arbor, Michigan 48109, United States
  • Weill Cornell Medicine - New York-Presbyterian Hospital
    New York, New York 10021, United States
  • Memorial Sloan Kettering Cancer Center
    New York, New York 10065, United States
  • Cleveland Clinic
    Cleveland, Ohio 44195, United States
  • OU Health Stephenson Cancer Center
    Oklahoma City, Oklahoma 73104, United States
  • Oregon Health & Sciences University - Knight Cancer Institute
    Portland, Oregon 97239, United States
  • Vanderbilt University
    Nashville, Tennessee 37232, United States
  • Sarah Cannon Research Institute
    Nashville, Tennessee 37239, United States
  • University of Utah
    Salt Lake City, Utah 84112, United States
08

References and documents

Publications

  • Meyer EH, Salhotra A, Gandhi AP, Pantin J, Patel SS, Hoeg RT, Gomez-Arteaga A, Faramand R, Tamari R, Waller EK, Kosuri S, Jimenez Jimenez AM, Holter-Chakrabarty J, Dholaria B, Chen YB, Hamilton BK, Magenau J, Eghtedar A, Murray JM, Pavlova A, Fernhoff NB, McClellan JS, Killian MS, Li A, Negrin RS, Oliai C. Orca-T vs allogeneic hematopoietic stem cell transplantation (Precision-T): a multicenter, randomized phase 3 trial. Blood. 2026 Mar 12;147(11):1168-1177. doi: 10.1182/blood.2025031313. PubMed 41385341 ↗

Study documents

  • Protocol and statistical analysis plan · Dec 13, 2024

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT05316701
Lead sponsor
Orca Biosystems, Inc.
Responsible party
Sponsor
First posted
Apr 7, 2022
Start date
Jun 21, 2022
Primary completion
Jul 15, 2024
Completion
Jul 2026 (estimated)
Results posted
Sep 26, 2025
Last update
Mar 4, 2026

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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