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

Acute Myeloid Leukemia Clinical Trial

— Orca-T  

Official 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05316701
• Other study ID #: Precision-T (PhIII component)
• Status: Recruiting
• Phase: Phase 3
• Start date: June 21, 2022
• Est. completion date: April 2027

Study information

• Verified date: April 2024
• Source: Orca Biosystems, Inc.
• Contact: James S McClellan, MD PhD
• Phone: 530 414 9743
• Email: info[@]orcabio.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. This posting represents the Phase III component of Precision-T. The Precision-T Ph1b component is described under NCT04013685.

Description:

Cross reference NCT04013685

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 174
• Est. completion date: April 2027
• Est. primary completion date: April 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Disease
• Acute Leukemia
• Acute Lymphoid Leukemia
• Acute Myeloid Leukemia
• Hematologic Neoplasms
• Leukemia
• Leukemia, Lymphoid
• Mixed Phenotype Acute Leukemia
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Preleukemia
• Syndrome
• Therapy-Related Myelodysplastic Syndrome
• Undifferentiated Leukemia

Intervention

Biological:
• Orca-T
an allogeneic stem cell and T-cell immunotherapy biologic
• Standard-of-Care
unmanipulated donor allograft

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 General Hospital	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	Ronald Regan 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	Salt Lake City	Utah
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	Chronic Graft-versus-Host-Disease-free Survival	An event for this time-to-event outcome is defined as death by any cause or moderate to severe cGVHD as defined by NIH consensus criteria, whichever is earlier.	Randomization through 730 days post transplant
Secondary	Time to moderate or severe cGVHD	An event for this time-to-event outcome is defined as time from randomization to the first onset of of moderate or severe cGVHD within 730 days after randomization. Death within 730 days after randomization without prior moderate or severe cGVHD is considered a competing event.	Randomization through 730 days post transplant
Secondary	Graft-versus-Host Disease and Relapse-free survival (GRFS) up to 1 year	GRFS is defined as the time from randomization to death from any cause, relapse, the first onset of grade 3 or 4 aGVHD (graded per MAGIC criteria), or the first onset of moderate or severe cGVHD (graded per NIH consensus criteria), whichever is earliest.	Day 0 through 365 days post-transplant
Secondary	Overall Survival	OS is defined as the time from randomization to death from any cause .	730 days after end of enrollment