Ignite Creation Date:
2024-05-06 @ 8:17 PM
Last Modification Date:
2024-10-26 @ 3:24 PM
Study NCT ID:
NCT06323525
Status:
RECRUITING
Last Update Posted:
2024-06-20
First Post:
2024-03-08
Brief Title:
TCR Reserved and Power3 Gene Knock-out Allogeneic CD19-targeting CAR-T Cell Therapy in rr B Cell Lymphoma
Sponsor:
Chinese PLA General Hospital
Organization:
Chinese PLA General Hospital
Study Overview
Official Title:
A Phase 12 Single-center Study Evaluating the Safety and Efficacy of TCR Reserved and Power3 Gene Knock-out Allogeneic CD19-targeting CAR-T Cell ATHENA-2 Therapy in Adults With RefractoryRelapsed B-cell Lymphoma
Status:
RECRUITING
Status Verified Date:
2024-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The safety and efficacy of the chimeric antigen receptor CAR-T a CD19-targeting TRAC and Power3 double genes deleted allogeneic CAR-T cell product are undergoing rigorous evaluation in non-Hodgkins lymphoma NHL subjects from our ATHENA trial NCT06014073 Unexpectedly expansion of the initial residual CD3-positive CAR T from products were measured in patients peripheral blood PB without exception Accompanying with host immune reconstitution and appearance of the detectable B cells the CD3-positive allogenic CAR T cells exhibited a compelling amplification advantage over CD3-negative CAR T cells The amplification of CD3-positive CAR T cell population dynamically suppressed host B cell recovery and presumably surveilled the recurrence or progression of tumors but did not induce typical Graft-versus-host-disease GvHD Additionally a series of in vitro experiments illustrated that the HLA-mismatched fratricide between host T cells and TCR-reserved Power3-deleted allogenic CAR T cells was markedly slashed which in combination with our observed clinical safety date supported the notion that only genomic deletion of Power3 gene in allo-CAR T cells is sufficient to overcome GvHD and host T cell-mediated rejection response
In the ATHENA-2 study our design is to preserve the expression of the TCR on T cells from healthy donors while selectively disabling the Power3 gene to prepare ATHENA-2 CAR T cells This approach harnesses the tonic signaling of CAR T cells resulting in enhanced persistence and improved response to treatment The purpose of this study is to evaluate the safety and efficacy of ATHENA-2 in B-cell NHL
In the ATHENA-2 study our design is to preserve the expression of the TCR on T cells from healthy donors while selectively disabling the Power3 gene to prepare ATHENA-2 CAR T cells This approach harnesses the tonic signaling of CAR T cells resulting in enhanced persistence and improved response to treatment The purpose of this study is to evaluate the safety and efficacy of ATHENA-2 in B-cell NHL
Detailed Description:
Phase 1 dose escalation
In phase 1 6-18 subjects will be enrolled Subjects will receive 3 doses of ATHENA-2 CAR-T cell therapy 1 106 cellskg 3 106 cellskg 6 106 cellskg increases from low dose to high dose according to the 3 3 principle
Three 3 subjects are enrolled in a cohort corresponding to a dose level If 1 subject in a cohort of 3 subjects experiences a dose-limiting toxicity DLT 3 additional subjects will be enrolled at the current dose level For safety purposes the administration of ATHENA-2 CAR T will be staggered by 28 days between the first two subjects in each cohort And for each of the remaining cohorts the administration of ATHENA-2 CAR-T will be staggered by 28 days before enter into the next cohort
Phase 2 expansion cohort
In phase 2 10 to 12 subjects will be enrolled and receive ATHENA-2 CAR-T cell infusion at dose of recommended phase 2 dose RP2D which will be determined based on the maximum tolerated dose MTD occurrence of DLT the obtained efficacy results pharmacokineticspharmacodynamics and other data according to the phase 1
Objectives
The primary objectives of the phase 1 are to evaluate the tolerability and safety of ATHENA-2 CAR-T in patients with rr B-cell NHL and determine RP2D The primary purpose of the phase 2 study is to evaluate the efficacy of ATHENA-2 CAR-T in the above population
In phase 1 6-18 subjects will be enrolled Subjects will receive 3 doses of ATHENA-2 CAR-T cell therapy 1 106 cellskg 3 106 cellskg 6 106 cellskg increases from low dose to high dose according to the 3 3 principle
Three 3 subjects are enrolled in a cohort corresponding to a dose level If 1 subject in a cohort of 3 subjects experiences a dose-limiting toxicity DLT 3 additional subjects will be enrolled at the current dose level For safety purposes the administration of ATHENA-2 CAR T will be staggered by 28 days between the first two subjects in each cohort And for each of the remaining cohorts the administration of ATHENA-2 CAR-T will be staggered by 28 days before enter into the next cohort
Phase 2 expansion cohort
In phase 2 10 to 12 subjects will be enrolled and receive ATHENA-2 CAR-T cell infusion at dose of recommended phase 2 dose RP2D which will be determined based on the maximum tolerated dose MTD occurrence of DLT the obtained efficacy results pharmacokineticspharmacodynamics and other data according to the phase 1
Objectives
The primary objectives of the phase 1 are to evaluate the tolerability and safety of ATHENA-2 CAR-T in patients with rr B-cell NHL and determine RP2D The primary purpose of the phase 2 study is to evaluate the efficacy of ATHENA-2 CAR-T in the above population
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None