RecruitingPhase 1Phase 2NCT07009002

BCOR and ZC3H12 Genes Knock-out CD19-targeting CAR-T Cell Therapy in r/r B Cell Lymphoma

A Phase I/II Single-center Study Evaluating the Safety and Efficacy of BCOR and ZC3H12 Genes Knock-out CD19-targeting CAR-T Cell Therapy in Adults With Refractory/Relapsed Refractory/Relapsed B-cell Lymphoma


Sponsor

Chinese PLA General Hospital

Enrollment

30 participants

Start Date

Jun 20, 2025

Study Type

INTERVENTIONAL

Conditions

Summary

In this single-center, single-arm, prospective, Phase 1/2 study, the safety and efficacy of autologous BCOR and ZC3H12 genes knock-out CD19-targeting chimeric antigen receptor (CAR) T-cell therapy will be evaluated in patients with refractory/relapsed (r/r) B-cell Lymphoma. For simplicity, we have termed these CD19 CAR T cells lacking ZC3H12A and BCOR as CAR19TIF( immortal-like and functional CD19 CAR T ) cells, reflecting their immortal-like and functional characteristics. In phase 1, 3 eligible patients will be enrolled and receive CAR19TIF cells at a initial dose of 5×10\^5 cells/kg. Based on the results, subsequently an additional 3-15 patients will be enrolled in a "3+3" dose-escalation/decline design to adjust the dose of CAR19TIF cells to achieve optimal safety and efficacy. The recommended Phase 2 dose (RP2D) will then be established. 10 to 12 subjects will be enrolled and receive CAR19TIF cells infusion at dose of RP2D.


Eligibility

Min Age: 18 YearsMax Age: 70 Years

Plain Language Summary

Simplified for easier understanding

This trial is testing a new type of immune cell therapy (called CAR-T) for people with a type of blood cancer called B-cell lymphoma that has come back or stopped responding to treatment. The therapy involves modifying a patient's own immune cells to better find and destroy cancer cells. **You may be eligible if...** - You are 18–70 years old - You have been diagnosed with relapsed or refractory B-cell non-Hodgkin's lymphoma (including DLBCL, follicular lymphoma grade 3B, or similar) - Your cancer has not responded to or has come back after at least 2 prior treatments - You have measurable disease on a scan **You may NOT be eligible if...** - Your lymphoma has spread to the brain or spinal fluid - You have had a prior organ or stem cell transplant recently - You have active hepatitis B, hepatitis C, or HIV - You are pregnant or breastfeeding 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

BIOLOGICALCAR19TIF cells

Phase 1 dose escalation/decline (3+3) : starting dose: 5×10\^5 cells/kg, According to effective expansion and clinical efficacy data, a descending dose escalation model will be adopted: such as 1×10\^5 cells/kg, 5×10\^4 cells/kg. If the 5×10\^5 cells/kg dose group does not achieve efficient expansion and clinical benefit, an ascending dose escalation model will be adopted, such as 2×10\^6 cells/kg, 6×10\^6 cells/kg. Phase 2 : dose of RP2D.

DRUGFludarabine

Intravenous fludarabine 25\~30 mg/m\^2/day on days -5, -4, and -3.

DRUGCyclophosphamide

Intravenous cyclophosphamide 250\~500 mg/m\^2/day on days -5, -4, and -3.


Locations(1)

Biotherapeutic Department of Chinsese PLA Gereral Hospital

Beijing, Beijing Municipality, China

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NCT07009002


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