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

NCT07216443 | Recruiting Phase 2 FDA Drug

• 1 other identifier: SERENE-T
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 5

Brief Summary

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).

Conditions

Mixed Phenotype Acute Leukemia; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Keywords

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Mixed Phenotype Acute Leukemia; Therapy-Related Myelodysplastic Syndrome; Hematopoietic Stem Cell Transplantation; Humans; Graft vs Host Disease; SERENE-T; ORCA-T; Disease; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Bone Marrow Diseases; Precancerous Conditions; Neoplasms by Site; Disease Attributes; Immunoproliferative Disorders; Immune System Diseases; Leukemia; Preleukemia; Hematologic Neoplasms; Syndrome; Acute Disease

Outcome Measures

Primary Outcomes (3)

• RIC Cohort: GVHD-free and relapse-free survival (GRFS)

  GRFS is defined as the time from the date of transplantation to the date of death from any cause, relapse, the first onset of grade 3 or 4 acute GVHD (graded per MAGIC criteria), or the first onset of moderate or severe chronic GVHD (graded per NIH consensus criteria), whichever is earliest.

  Day 0 through day +365 after transplantation

• NMA Cohort: Incidence of neutrophil engraftment

  Incidence of neutrophil engraftment is defined as achieving an ANC ≥500/mm3 for 3 consecutive days by day +28. The first of the 3 days will be designated the day of engraftment. If the ANC never drops below 500/mm3, day +1 will be designated the day of engraftment.

  Day 0 through day +28 after transplantation

• NMA Cohort: Time to neutrophil engraftment

  The first of the 3 days will be designated the day of engraftment. If the ANC never drops below 500/mm3, day +1 will be designated the day of engraftment.

  Day 0 through day +28 after transplantation

Secondary Outcomes (20)

• Safety of Orca-T

  Day 0 through day +100 after transplantation

• Incidence of serious infections

  Day 0 through day +365 after transplantation

• Severity of serious infection

  Day 0 through day +365 after transplantation

• Overall survival

  Day 0 through day +730 after transplantation

• Non-relapse mortality

  Day 0 through day +730 after transplantation

Study Arms (1)

Orca-T

EXPERIMENTAL

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

Biological: Orca-T

Interventions

Orca-T BIOLOGICAL

An allogeneic stem cell and T-cell immunotherapy biologic

Orca-T

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years at the time of enrollment
• Diagnosed with 1 of the following diseases:
• 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.
• 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.
• Planned to undergo 1 of the following preparative regimens as per Investigator discretion:
• RIC cohort: Planned RIC-alloHCT including RIC regimen with TBI/thiotepa/fludarabine
• NMA cohort: Planned NMA-alloHCT including NMA regimen with fludarabine/cyclophosphamide/TBI
• Identified related or unrelated donor who is an 8/8 match for HLA-A, -B, -C, and -DRB1
• Estimated glomerular filtration rate ≥30 mL/minute
• Cardiac ejection fraction at rest ≥40% or shortening fraction of ≥22% by echocardiogram or radionuclide scan (MUGA)
• Diffusing capacity of the lung for carbon monoxide (adjusted for hemoglobin) ≥40%
• Negative serum or urine β-HCG test in persons of childbearing potential
• Alanine transaminase (ALT)/aspartate transaminase (AST) \<5 times the upper limit of normal (ULN)
• Total bilirubin \<3 × ULN
• Deemed ineligible for a fully myeloablative alloHCT per assessment of the principal investigator

You may not qualify if:

• Prior alloHCT
• 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 antidonor HLA antibodies against a mismatched allele in the selected donor
• Karnofsky performance score \<60%
• For RIC cohort only: HCT-Specific Comorbidity Index (HCT-CI) ≥6
• Uncontrolled bacterial, viral, or fungal infection (currently taking antimicrobial therapy and with progression or no clinical improvement) at the time of enrollment
• 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
• 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 malignancy within 1 year except nonmelanoma skin cancer that has been curatively resected
• Psychosocial circumstances that preclude the participant being able to go through transplantation or participate responsibly in follow-up care
• Persons who are pregnant or breastfeeding

Sponsors & Collaborators

• Orca Biosystems, Inc.: lead

Study Sites (5)

UCLA Department of Medicine

Los Angeles, California, 90095, United States

RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33612, United States

NOT YET RECRUITING

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

RECRUITING

Oregon Health and Science University

Portland, Oregon, 97239, United States

RECRUITING

Vanderbilt University, Ingram Cancer Center

Nashville, Tennessee, 37232, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Leukemia, Biphenotypic, Acute; Graft vs Host Disease; Disease; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Bone Marrow Diseases; Precancerous Conditions; Neoplasms by Site; Disease Attributes; Immunoproliferative Disorders; Immune System Diseases; Leukemia; Preleukemia; Hematologic Neoplasms; Syndrome; Acute Disease

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Chief Medical Officer

CONTACT

650-246-9601; info@orcabio.com

Medical Director

CONTACT

650-246-9601; info@orcabio.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: September 29, 2025
• First Posted: October 14, 2025
• Study Start: December 9, 2025
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)