RecruitingPhase 1Phase 2NCT06321289

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

Sponsor

Chinese PLA General Hospital

Enrollment

30 participants

Start Date

Mar 20, 2024

Study Type

INTERVENTIONAL

Conditions

Non-hodgkin Lymphoma,B Cell

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.

Eligibility

Min Age: 18 YearsMax Age: 75 Years

Plain Language Summary

Simplified for easier understanding

This study is testing a new type of immune cell therapy called STAR T cell therapy for people with B-cell lymphoma (a type of blood cancer) that has come back or stopped responding to treatment. These special T cells are engineered from a donor to target a protein called CD19 found on cancer cells. **You may be eligible if:** - You are between 18 and 75 years old - You have been diagnosed with CD19-positive B-cell lymphoma (including DLBCL, follicular lymphoma, mantle cell lymphoma, or others) - Your cancer has relapsed after at least 2 prior treatments, or was resistant to initial treatment - You have received prior chemotherapy including anti-CD20 antibody therapy - Your heart, kidneys, liver, and lungs are functioning adequately - Your overall health score (ECOG) is 0–2 **You may NOT be eligible if:** - You have cancer that has spread to the brain or spinal fluid - You have had a prior bone marrow or organ transplant - You have received CAR-T therapy or other gene-modified cell therapy before - You have previously had CD19-targeted therapy - You are pregnant or breastfeeding - You have uncontrolled infections, HIV, or active hepatitis B or C - You have had a stroke or brain bleed in the last 3 months Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

BIOLOGICALAllogeneic 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.

DRUGFludarabine

Intravenous fludarabine 30-50 mg/m\^2/day on days -5, -4, and -3.

DRUGCyclophosphamide

Intravenous cyclophosphamide 500-1000 mg/m\^2/day on days -5, -4, and -3.