NCT06321289

Allogeneic TRAC Locus-inserted CD19-targeting STAR T Cell Therapy in r/r B-NHL

Allogeneic TRAC Locus-inserted CD19-targeting Synthetic T-cell Receptor Antigen Receptor (STAR) T Cells for Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: Chinese PLA General Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

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 (r/r) 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)-A/B, 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 1/2 study, the safety and efficacy of allogeneic CD19-targeting STAR T cell therapy will be evaluated in patients with r/r 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 × 10\^6 cells/kg, 6 × 10\^6 cells/kg, 1.8 × 10\^7 cells/kg) 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 0/3, 3 patients were enrolled in the next high-dose group. 2. If the incidence of DLT was 1/3, 3 patients were enrolled at the same dose; If the incidence of DLT was 1/3 + 0/3, 3 patients were enrolled in the next high-dose group. If the incidence of DLT was 1/3 + 1/3, this dose was defined as maximum tolerated dose (MTD); If the incidence of DLT was 1/3 + 2/3 or 1/3 + 3/3, the previous dose was MTD. 3. If the incidence of DLT was 2/3 or 3/3, 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.

Conditions

• Non-hodgkin Lymphoma,B Cell

Interventions

Type	Name	Description
BIOLOGICAL	Allogeneic CD19-STAR T cell	Phase 1 dose escalation (3+3): dose 1 (2×10\^6 cells/kg), dose 2 (6×10\^6 cells/kg), dose 3 (1.8×10\^7 cells/kg); Phase 2: dose of RP2D. No more than 5 × 10\^4 per kilogram of allogenic residual TCR-positive T cells harbouring in grafts can only be released for recipient infusion.
DRUG	Fludarabine	Intravenous fludarabine 30-50 mg/m\^2/day on days -5, -4, and -3.
DRUG	Cyclophosphamide	Intravenous cyclophosphamide 500-1000 mg/m\^2/day on days -5, -4, and -3.

Timeline

• Start date: 2024-03-20
• Primary completion: 2026-03-20
• Completion: 2027-03-20
• First posted: 2024-03-20
• Last updated: 2024-03-25

Locations

2 sites across 1 country: China