Ignite Creation Date:
2024-05-06 @ 8:18 PM
Last Modification Date:
2024-10-26 @ 3:24 PM
Study NCT ID:
NCT06321289
Status:
RECRUITING
Last Update Posted:
2024-03-25
First Post:
2024-03-13
Brief Title:
Allogeneic TRAC Locus-inserted CD19-targeting STAR T Cell Therapy in rr B-NHL
Sponsor:
Chinese PLA General Hospital
Organization:
Chinese PLA General Hospital
Study Overview
Official Title:
Allogeneic TRAC Locus-inserted CD19-targeting Synthetic T-cell Receptor Antigen Receptor STAR T Cells for RelapsedRefractory B-cell Non-Hodgkins Lymphoma
Status:
RECRUITING
Status Verified Date:
2024-03
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 team has developed the synthetic T cell receptor TCR and antigen receptor STAR T cells which were demonstrated safety in relapsed or refractory rr B-cell non-Hodgkin s lymphoma B-NHL NCT05631912 Based on this research allogeneic STAR-T cell products utilized the CRISPR-Cas9 gene editing tool to knock out endogenous receptor α constant TRAC human leukocyte antigen HLA-AB CIITA and programmed death 1 PD-1 genes simultaneously in T cells from healthy donors and integrated the STAR molecule into the TRAC locus using adenovirus associated virus This strategy can reduce graft-versus-host-disease GvHD toxicity and host-versus-graft response decrease the sensitivity of STAR T cells to immunosuppressive signals and improve their anti-tumor activity In this single center prospective open-label single-arm phase 12 study the safety and efficacy of allogeneic CD19-targeting STAR T cell therapy will be evaluated in patients with rr B-NHL
Detailed Description:
Phase 1 dose escalation
In phase 1 6 to 18 subjects will be enrolled Subjects will receive 3 doses of allogeneic CD19-STAR T cell therapy 2 106 cellskg 6 106 cellskg 18 107 cellskg from low dose to high dose according to the 3 3 principle
1 Three patients were enrolled in the lowest dose group
2 Subsequent patients were enrolled according to the following rules
1 If the incidence of dose limiting toxicity DLT was 03 3 patients were enrolled in the next high-dose group
2 If the incidence of DLT was 13 3 patients were enrolled at the same dose If the incidence of DLT was 13 03 3 patients were enrolled in the next high-dose group If the incidence of DLT was 13 13 this dose was defined as maximum tolerated dose MTD If the incidence of DLT was 13 23 or 13 33 the previous dose was MTD
3 If the incidence of DLT was 23 or 33 the previous dose was MTD
To ensure the safety of the subjects the first subject in each dose group was observed for at least 28 days after the cell infusion If no DLT occurred the remaining two subjects could be enrolled and treated at the same dose level The safety data of all subjects in each dose group until day 28 should be reviewed and tolerated before proceeding to the next dose group trial No dose escalation was allowed for the same subject during the trial If a subject drop out during the observation period due to non-DLT reasons new subjects should be enrolled to make up for the number of subjects who drop out
Phase 2 expansion cohort
In phase 2 10 to 12 subjects will be enrolled and receive allogeneic CD19-STAR T cell infusion at dose of recommended phase 2 dose RP2D which will be determined based on the MTD occurrence of DLT the obtained efficacy results pharmacokinetics pharmacodynamics and other data according to the phase 1
Objectives
The primary objectives of the phase 1 are to evaluate the tolerability safety and determine RP2D The primary purpose of the phase 2 study is to evaluate the efficacy
In phase 1 6 to 18 subjects will be enrolled Subjects will receive 3 doses of allogeneic CD19-STAR T cell therapy 2 106 cellskg 6 106 cellskg 18 107 cellskg from low dose to high dose according to the 3 3 principle
1 Three patients were enrolled in the lowest dose group
2 Subsequent patients were enrolled according to the following rules
1 If the incidence of dose limiting toxicity DLT was 03 3 patients were enrolled in the next high-dose group
2 If the incidence of DLT was 13 3 patients were enrolled at the same dose If the incidence of DLT was 13 03 3 patients were enrolled in the next high-dose group If the incidence of DLT was 13 13 this dose was defined as maximum tolerated dose MTD If the incidence of DLT was 13 23 or 13 33 the previous dose was MTD
3 If the incidence of DLT was 23 or 33 the previous dose was MTD
To ensure the safety of the subjects the first subject in each dose group was observed for at least 28 days after the cell infusion If no DLT occurred the remaining two subjects could be enrolled and treated at the same dose level The safety data of all subjects in each dose group until day 28 should be reviewed and tolerated before proceeding to the next dose group trial No dose escalation was allowed for the same subject during the trial If a subject drop out during the observation period due to non-DLT reasons new subjects should be enrolled to make up for the number of subjects who drop out
Phase 2 expansion cohort
In phase 2 10 to 12 subjects will be enrolled and receive allogeneic CD19-STAR T cell infusion at dose of recommended phase 2 dose RP2D which will be determined based on the MTD occurrence of DLT the obtained efficacy results pharmacokinetics pharmacodynamics and other data according to the phase 1
Objectives
The primary objectives of the phase 1 are to evaluate the tolerability safety and determine RP2D The primary purpose of the phase 2 study is to evaluate the efficacy
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