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

Phase 1

Active, not recruiting

• Conditions: Acute Myeloid Leukemia; Acute Lymphoid Leukemia; Chronic Myeloid Leukemia; Acute Leukemia; Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN); Myelodysplastic Syndromes
• Interventions: Biological: Orca-T

• Registration Number: NCT04013685
• Lead Sponsor: Orca Biosystems, Inc.

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-07-03
• Study First Submitted QC: 2019-07-08
• Study First Posted: 2019-07-10
• Study Start: 2019-11-21
• Status Verified: 2024-07
• Primary Completion: 2024-07-26
• Last Update Submitted: 2024-07-31
• Last Update Posted: 2024-08-02
• Study Completion: 2026-07

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 255

Inclusion Criteria

Recipients must meet all of the following criteria:

1. Patients must diagnosed with one 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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Subjects with Acute Leukemia or Myelodysplasic Syndrome, or BPDCN	Orca-T	This is a non-randomized, single-arm study. All enrolled subjects will receive an allogeneic HCT with the Orca-T product.

Primary Outcome Measures

Name	Time	Method
The incidence of primary graft failure	365 days	The incidence of primary graft failure
The incidence of grade 3 or 4 aGVHD	180 days	The incidence of grade 3 or 4 aGVHD

Secondary Outcome Measures

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

Trial Locations

Locations (21)

City of Hope; 🇺🇸 Duarte, California, United States

UC Davis; 🇺🇸 Sacramento, California, United States

Stanford Health Care; 🇺🇸 Stanford, California, United States

Moffitt Cancer Center; 🇺🇸 Tampa, Florida, United States

University of Michigan Health System - Michigan Medicine; 🇺🇸 Ann Arbor, Michigan, United States

Weill Cornell Medicine - New York-Presbyterian Hospital; 🇺🇸 New York, New York, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

Winship Cancer Institute - Emory University; 🇺🇸 Atlanta, Georgia, United States

Ronald Reagan UCLA Medical Center; 🇺🇸 Los Angeles, California, United States

University of Chicago; 🇺🇸 Chicago, Illinois, United States

Massachusetts; 🇺🇸 Boston, Massachusetts, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

University of Miami Hospital and Clinics - Sylvester Comprehensive Cancer Center; 🇺🇸 Miami, Florida, United States

University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Sarah Cannon Research Institute; 🇺🇸 Nashville, Tennessee, United States

Vanderbilt University; 🇺🇸 Nashville, Tennessee, United States

University of Utah - Huntsman Cancer Institute; 🇺🇸 Salt Lake City, Utah, United States

The University of Kansas Hospital; 🇺🇸 Kansas City, Kansas, United States

Colorado Blood Cancer Institute; 🇺🇸 Denver, Colorado, United States

OU Health Stephenson Cancer Center; 🇺🇸 Oklahoma City, Oklahoma, United States

Oregon Health & Sciences University - Knight Cancer Institute; 🇺🇸 Portland, Oregon, United States