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

Sponsor

Orca Biosystems, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05316701

Collaborator

(none)

174

Enrollment

Locations

Arms

69.4

Anticipated Duration (Months)

12.4

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will compare the safety and efficacy between patients receiving an engineered donor graft ("Orca-T", a T-cell-Depleted Graft With Additional Infusion of Conventional T Cells and Regulatory T Cells) or standard-of-care (SOC) control in participants undergoing myeloablative allogeneic hematopoietic cell transplant transplantation (MA-alloHCT) for hematologic malignancies. This posting represents the Phase III component of Precision-T. The Precision-T Ph1b component is described under NCT04013685.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia Acute Lymphoid Leukemia Mixed Phenotype Acute Leukemia Undifferentiated Leukemia High-risk Myelodysplastic Syndrome Acute Leukemia Therapy-Related Myelodysplastic Syndrome	Biological: Orca-T Biological: Standard-of-Care	Phase 3

Detailed Description

Cross reference NCT04013685

Study Design

Study Type:

Interventional

Anticipated Enrollment :

174 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

The Phase III is a randomized, open-label, multicenter study comparing outcomes between patients receiving Orca-T followed by single-agent tacrolimus or standard-of-care (SOC) control followed by dual agent, tacrolimus-based Graft-versus-Host-Disease (GVHD) prophylaxis regimenThe Phase III is a randomized, open-label, multicenter study comparing outcomes between patients receiving Orca-T followed by single-agent tacrolimus or standard-of-care (SOC) control followed by dual agent, tacrolimus-based Graft-versus-Host-Disease (GVHD) prophylaxis regimen

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized Phase III Trial for 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

Actual Study Start Date :

Jun 21, 2022

Anticipated Primary Completion Date :

Apr 1, 2024

Anticipated Study Completion Date :

Apr 1, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Orca-T For patients randomized to the Orca-T arm, Orca-T will be administered after myeloablative conditioning regimen. Single-agent GVHD prophylaxis with tacrolimus will be administered following Tcon infusion (generally Day +3).	Biological: Orca-T engineered donor allograft Other Names: TregGraft
Active Comparator: Standard of Care alloHCT Control For patients randomized to the standard-of-care control arm, an unmanipulated allograft derived from the peripheral blood of a matched donor will be administered after a myeloablative conditioning regimen. Dual-agent prophylaxis consisting of tacrolimus plus methotrexate will be administered starting on Day -3.	Biological: Standard-of-Care unmanipulated donor allograft Other Names: SOC

Arm

Intervention/Treatment

Experimental: Orca-T

For patients randomized to the Orca-T arm, Orca-T will be administered after myeloablative conditioning regimen. Single-agent GVHD prophylaxis with tacrolimus will be administered following Tcon infusion (generally Day +3).

Biological: Orca-T

engineered donor allograft

Other Names:

TregGraft

Active Comparator: Standard of Care alloHCT Control

For patients randomized to the standard-of-care control arm, an unmanipulated allograft derived from the peripheral blood of a matched donor will be administered after a myeloablative conditioning regimen. Dual-agent prophylaxis consisting of tacrolimus plus methotrexate will be administered starting on Day -3.

Biological: Standard-of-Care

unmanipulated donor allograft

Other Names:

SOC

Outcome Measures

Primary Outcome Measures

Chronic Graft-versus-Host-Disease-free Survival [Randomization through 730 days post transplant]
An event for this time-to-event outcome is defined as death by any cause of moderate to severe cGVHD as defined by NIH consensus criteria

Secondary Outcome Measures

Graft-versus-Host-Disease and Relapse-free survival (GRFS) [Day 0 through 365 days post-transplant]
An event for this time-to-event outcome is defined as survival free of death from any cause, relapse, Grade 3-4 aGVHD (graded per MAGIC), and moderate to severe cGVHD (graded per NIH consensus criteria).
Moderate to severe chronic graft-versus-host-disease [Day 0 through 365 days post-transplant]
An event for this time-to-event outcome is defined as moderate to severe cGVHD as defined by NIH consensus criteria.
Relapse-free survival [Day 0 through 730 days post-transplant]
Survival free of death from relapse.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 high to very high risk or therapy-related/secondary MDS
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope	Duarte	California	United States	91010
2	Ronald Regan UCLA Medical Center	Los Angeles	California	United States	90095
3	UC Davis	Sacramento	California	United States	95817
4	Stanford Health Care	Stanford	California	United States	94305
5	University of Miami Hospital and Clinics - Sylvester Comprehensive Cancer Center	Miami	Florida	United States	33136
6	Moffitt Cancer Center	Tampa	Florida	United States	33612
7	Winship Cancer Institute - Emory University	Atlanta	Georgia	United States	30322
8	University of Chicago	Chicago	Illinois	United States	60637
9	Weill Cornell Medicine - New York-Presbyterian Hospital	New York	New York	United States	10021
10	Oregon Health & Sciences University - Knight Cancer Institute	Portland	Oregon	United States	97239
11	Vanderbilt University	Nashville	Tennessee	United States	37232
12	Sarah Cannon Research Institute	Nashville	Tennessee	United States	37239
13	Methodist Hospital - Texas Transplant Institute	San Antonio	Texas	United States	78229
14	University of Utah	Salt Lake City	Utah	United States	84112