Trial of Orca-T Following Reduced Intensity or Nonmyeloablative Conditioning in Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome

NCT ID: NCT07216443

Last Updated: 2026-01-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

80 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-12-09

Study Completion Date

2028-12-31

Brief Summary

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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).

Detailed Description

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This study is a multicenter, open-label phase 2 trial of Orca-T in adults with acute myeloid leukemia or myelodysplastic syndrome who are not able to receive myeloablative (high intensity) conditioning and are eligible for reduced intensity conditioning (RIC)-alloHCT or non-myeloablative (NMA)-alloHCT with an 8/8 human leukocyte antigen (HLA)-matched related or unrelated donor. The trial is designed to further characterize the safety and tolerability of Orca-T and to perform an initial assessment of the efficacy of Orca-T in participants eligible for RIC-alloHCT or NMA-alloHCT.

Participants will receive Orca-T after the investigator's choice from the RIC and NMA regimens followed by single-agent graft-versus-host disease (GVHD) prophylaxis with tacrolimus.

Prior to the initiation of this study (the SERENE-T Study), a phase 1 study (clinicaltrials.gov number: NCT05088356) was conducted to examine the safety and efficacy of Orca-T in participants receiving RIC-alloHCT. Participants have also been treated previously with Orca-T during an ongoing phase 1b/3 study (NCT05316701 and NCT04013685) in participants receiving a MAC regimen. The results of these studies have prompted Orca Bio to further evaluate Orca-T in participants receiving RIC or NMA.

Conditions

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Leukemia, Myeloid, Acute Myelodysplastic Syndromes Mixed Phenotype Acute Leukemia

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

This is a multicenter, open-label phase 2 trial of Orca-T in adults with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) who are eligible for RIC-alloHCT or NMA-alloHCT with an 8/8 HLA-matched related or unrelated donor. Participants will receive Orca-T after the investigator's choice from the RIC and NMA regimens allowed as per protocol. Single-agent GVHD prophylaxis with tacrolimus will be administered.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Orca-T

Participants will receive \[RIC or NMA conditioning\] + Orca-T + single-agent tacrolimus based on eligibility and investigator's choice of conditioning regimen.

Group Type EXPERIMENTAL

Orca-T

Intervention Type BIOLOGICAL

An allogeneic stem cell and T-cell immunotherapy biologic

Interventions

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Orca-T

An allogeneic stem cell and T-cell immunotherapy biologic

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

1. Age ≥18 years at the time of enrollment
2. Diagnosed with 1 of the following diseases:

1. 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.
2. 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.
3. Planned to undergo 1 of the following preparative regimens as per Investigator discretion:

1. RIC cohort: Planned RIC-alloHCT including RIC regimen with TBI/thiotepa/fludarabine
2. NMA cohort: Planned NMA-alloHCT including NMA regimen with fludarabine/cyclophosphamide/TBI
4. Identified related or unrelated donor who is an 8/8 match for HLA-A, -B, -C, and -DRB1
5. Estimated glomerular filtration rate ≥30 mL/minute
6. Cardiac ejection fraction at rest ≥40% or shortening fraction of ≥22% by echocardiogram or radionuclide scan (MUGA)
7. Diffusing capacity of the lung for carbon monoxide (adjusted for hemoglobin) ≥40%
8. Negative serum or urine β-HCG test in persons of childbearing potential
9. Alanine transaminase (ALT)/aspartate transaminase (AST) \<5 times the upper limit of normal (ULN)
10. Total bilirubin \<3 × ULN
11. Deemed ineligible for a fully myeloablative alloHCT per assessment of the principal investigator

Exclusion Criteria

1. Prior alloHCT
2. Currently receiving corticosteroids or other immunosuppressive therapy. Topical corticosteroids or oral systemic corticosteroid doses less than or equal to 10 mg/day are allowed.
3. Planned donor lymphocyte infusion (DLI)
4. Planned pharmaceutical in vivo or ex vivo T-cell depletion
5. Recipient-positive antidonor HLA antibodies against a mismatched allele in the selected donor
6. Karnofsky performance score \<60%
7. For RIC cohort only: HCT-Specific Comorbidity Index (HCT-CI) ≥6
8. Uncontrolled bacterial, viral, or fungal infection (currently taking antimicrobial therapy and with progression or no clinical improvement) at the time of enrollment
9. 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
10. Known allergy or hypersensitivity to or intolerance of tacrolimus
11. Documented allergy or hypersensitivity to iron dextran or bovine, murine, algal, or Streptomyces avidinii proteins
12. Any uncontrolled autoimmune disease requiring active immunosuppressive treatment
13. Concurrent malignancy within 1 year except nonmelanoma skin cancer that has been curatively resected
14. Psychosocial circumstances that preclude the participant being able to go through transplantation or participate responsibly in follow-up care
15. Persons who are pregnant or breastfeeding
16. 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.
17. 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Orca Biosystems, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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UCLA Department of Medicine

Los Angeles, California, United States

Site Status RECRUITING

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status NOT_YET_RECRUITING

Oregon Health and Science University

Portland, Oregon, United States

Site Status RECRUITING

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Chief Medical Officer

Role: CONTACT

650-246-9601

Medical Director

Role: CONTACT

650-246-9601

Facility Contacts

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Caspian Oliai

Role: primary

310-794-0824

Siddhartha Reddy

Role: primary

551-996-5900

Arpita Gandhi

Role: primary

503-494-5058

Bhagirathbhai Dholaria

Role: primary

615-875-3112

Other Identifiers

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SERENE-T

Identifier Type: -

Identifier Source: org_study_id

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