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

A Phase Ib 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.

Study Overview

• Status: Active, not recruiting
• Conditions: Acute Myeloid Leukemia; Myelodysplastic Syndromes; Chronic Myeloid Leukemia; Acute Leukemia; Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN); Acute Lymphoid Leukemia
• Intervention / Treatment: Biological: Orca-T

• Study Type: Interventional
• Enrollment (Actual): 155
• Phase: Phase 1

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
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • The University of Kansas Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts
  • 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, 37203
      • Sarah Cannon Research Institute
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University
  • Texas
    • Houston, Texas, United States, 77054
      • University of Texas MD Anderson Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah - Huntsman Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

Recipients must meet all of the following criteria:

1. Patients must be diagnosed with 1 of the following histopathologically confirmed diseases, for which a myeloablative hematopoietic stem cell transplant (HCT) is planned:

   A) Acute myeloid, lymphoid, or mixed phenotype/undifferentiated leukemia who are not in CR or CRi (active disease) and/or MDS with >10% to <20% bone marrow blast burden (ages 18 to 75 years)

   B) Acute leukemia in CR/CRi or MDS that is DRI intermediate to high risk (ages 66 to 75 years)

   C) BPDCN (ages 18 to 65 years)

   D) Participants aged 18 to 65 who would be eligible for the Phase 3 component of Precision-T except for mild impairments of renal and/or hepatic function as defined by an eGFR of 50 to <60 mL/min and/or a total bilirubin of >ULN to ≤2 x ULN and diagnosed with either of the following:

   i. Acute myeloid, lymphoid, or mixed phenotype/undifferentiated leukemia that is in CR/CRi and DRI intermediate to high risk

   a) MDS that is DRI intermediate to high risk

   E) Acute or chronic leukemia in remission that is DRI low risk (ages 18 to 65 years), including the following:

   i. CML in chronic phase but with a history of accelerated phase or blast crisis or who are resistant to or intolerant of more than 1 first- and second-generation tyrosine kinase inhibitors

   ii. Acute myeloid leukemia (AML) with inv(16) without accompanying complex cytogenetics

2. Patients must be matched to a 8/8 HLA-matched related or unrelated donor
3. Estimated glomerular filtration rate (eGFR) >50 mL/minute
4. Cardiac ejection fraction at rest ≥45% or shortening fraction of ≥27% by echocardiogram or radionuclide scan (MUGA)
5. Diffusing capacity of the lung for carbon monoxide (DLCO) (adjusted for hemoglobin) ≥50%
6. Total bilirubin <2 times upper limit of normal (ULN) (patients with Gilbert's syndrome may be included where hemolysis has been excluded) and ALT/AST <3 times ULN

Key Exclusion Criteria:

Recipients meeting any of the following exclusion criteria will not be eligible:

1. History of prior allogeneic HCT
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. Pre-planned donor lymphocyte infusion (DLI)
4. Planned pharmaceutical in vivo or ex vivo T cell depletion
5. Positive for anti-donor HLA antibodies against an allele in the selected donor
6. Karnofsky performance score <70%
7. Hematopoietic cell transplantation-specific Comorbidity Index (HCT-CI) >4
8. Uncontrolled bacterial, viral or fungal infections (currently taking antimicrobial therapy and with progression or no clinical improvement) at time of enrollment
9. Seropositive for HIV-1 or -2 antibody, HTLV-1 or -2 antibody, Hepatitis B sAg, or Hepatitis C antibody
10. Any uncontrolled autoimmune disease requiring active immunosuppressive treatment
11. Concurrent malignancies or active disease within 1 year, except non-melanoma skin cancers that have been curatively resected
12. Women who are pregnant or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Subjects with Acute Leukemia or Myelodysplastic Syndrome, or BPDCN; This is a non-randomized, single-arm study. All enrolled subjects will receive an allogeneic HCT with the Orca-T product.	Biological: Orca-T; an allogeneic stem cell and T-cell immunotherapy biologic

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of primary graft failure	The incidence of primary graft failure	365 days
The incidence of grade 3 or 4 aGVHD	The incidence of grade 3 or 4 aGVHD	180 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-year overall survival (OS)	1-year overall survival (OS)	365 days
1 year graft-versus-host-disease-free and relapse-free survival (GRFS)	1 year graft-versus-host-disease-free and relapse-free survival (GRFS)	365 days
incidence and severity of acute and chronic graft vs host disease (GvHD)	incidence and severity of acute and chronic graft vs host disease (GvHD)	365 days
incidence of serious infections	incidence of serious infections	365 days
incidence of engraftment	incidence of engraftment of platelets and neutrophils	28 days

Collaborators and Investigators

• Sponsor: Orca Biosystems, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 21, 2019
• Primary Completion (Actual): April 30, 2025
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: July 3, 2019
• First Submitted That Met QC Criteria: July 8, 2019
• First Posted (Actual): July 10, 2019

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 29, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: hematopoietic stem cell transplantation; acute leukemia; Myelodysplastic syndromes; matched related donor; matched unrelated donor
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Chronic Disease; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Skin Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma; Leukemia, Myeloid; Bone Marrow Diseases; Leukemia, Lymphoid; Leukemia; Skin Neoplasms; Myeloproliferative Disorders; Hematologic Neoplasms; Histiocytic Disorders, Malignant; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Blastic Plasmacytoid Dendritic Cell Neoplasm
• Other Study ID Numbers: Precision-T (PhIb component)

Drug and device information, study documents

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