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

Acute Myeloid Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04013685
• Other study ID #: Precision-T (PhIb component)
• Status: Recruiting
• Phase: Phase 1
• Start date: November 21, 2019
• Est. completion date: July 2026

Study information

• Verified date: April 2024
• Source: Orca Biosystems, Inc.
• Contact: James S McClellan, MD PhD
• Phone: 530-414-9743
• Email: info[@]orcabiosystems.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 255
• Est. completion date: July 2026
• Est. primary completion date: July 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Key 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 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

Related Conditions & MeSH terms

• Acute Leukemia
• Acute Lymphoid Leukemia
• Acute Myeloid Leukemia
• Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)
• Chronic Myeloid Leukemia
• Hematologic Neoplasms
• Leukemia
• Leukemia, Lymphoid
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Myelodysplastic Syndromes
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Preleukemia

Intervention

Biological:
• Orca-T
an allogeneic stem cell and T-cell immunotherapy biologic

Locations

Country	Name	City	State
United States	University of Michigan Health System - Michigan Medicine	Ann Arbor	Michigan
United States	Winship Cancer Institute - Emory University	Atlanta	Georgia
United States	Massachusetts	Boston	Massachusetts
United States	University of Chicago	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	City of Hope	Duarte	California
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	The University of Kansas Hospital	Kansas City	Kansas
United States	Ronald Reagan UCLA Medical Center	Los Angeles	California
United States	University of Miami Hospital and Clinics - Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Vanderbilt University	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Weill Cornell Medicine - New York-Presbyterian Hospital	New York	New York
United States	OU Health Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Oregon Health & Sciences University - Knight Cancer Institute	Portland	Oregon
United States	UC Davis	Sacramento	California
United States	University of Utah - Huntsman Cancer Institute	Salt Lake City	Utah
United States	Texas Transplant Institute	San Antonio	Texas
United States	Stanford Health Care	Stanford	California
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Orca Biosystems, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The incidence of primary graft failure	The incidence of primary graft failure	365 days
Primary	The incidence of grade 3 or 4 aGVHD	The incidence of grade 3 or 4 aGVHD	180 days
Secondary	1-year overall survival (OS)	1-year overall survival (OS)	365 days
Secondary	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
Secondary	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
Secondary	incidence of serious infections	incidence of serious infections	365 days
Secondary	incidence of engraftment	incidence of engraftment of platelets and neutrophils	28 days