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NCT Number: NCT05316701

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

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

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Key information

Conditions

Acute Myeloid Leukemia Acute Leukemia Acute Lymphoid Leukemia Bone Marrow Diseases Hematologic Diseases Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Leukemia Leukemia, Biphenotypic, Acute Leukemia, Lymphoid Leukemia, Myeloid Leukemia, Myeloid, Acute Lymphatic Diseases Lymphoproliferative Disorders Mixed Phenotype Acute Leukemia Myelodysplastic Syndrome Myelodysplastic Syndromes Neoplasms Neoplasms by Histologic Type Precursor Cell Lymphoblastic Leukemia-Lymphoma Therapy-Related Myelodysplastic Syndrome Undifferentiated Leukemia

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

City of Hope, Duarte, California, United States

Loading trial locations.

About this study

Cross reference NCT04013685

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Orca-T

Biological

an allogeneic stem cell and T-cell immunotherapy biologic

Standard-of-Care

Biological

unmanipulated donor allograft

Other names: SOC

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)

    Time frame: Day 0 through 730 days after transplantation

    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.

Secondary outcomes

  1. Event Rate at 12 Months for Time to Moderate or Severe cGVHD Per EAC

    Time frame: Day 0 through 730 days after transplantation

    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.

  2. Event-free at 12 Months for Overall Survival (OS)

    Time frame: Up to 730 days after end of enrollment

    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.

  3. Event-free Rate at 12 Months for Graft-versus-host Disease-free and Relapse-free Survival (GRFS) Per EAC

    Time frame: Day 0 through 730 days after transplantation

    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.

Sponsors and collaborators

Lead sponsor

Orca Biosystems, Inc.

Industry

Registry information

Official study title

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

Acronym: Orca-T

Important dates

Study start
2022
Primary completion
2024
Study completion
2026
First posted
Apr 7, 2022
Registry last updated
Mar 4, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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