RecruitingPhase 1Phase 2NCT07008885

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

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 B-cell Acute Lymphoblastic Leukaemia

Sponsor

Chinese PLA General Hospital

Enrollment

30 participants

Start Date

Jun 20, 2025

Study Type

INTERVENTIONAL

Conditions

Acute Lymphocytic Leukemia

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 acute lymphoblastic leukaemia (B-ALL). In phase 1, 3 eligible patients will be enrolled and receive BCOR and ZC3H12 genes knock-out CD19 CAR T cell therapy 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 BCOR and ZC3H12 genes knock-out CD19 CAR T 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 BCOR and ZC3H12 genes knock-out CD19 CAR T cell infusion at dose of RP2D.

Eligibility

Min Age: 18 YearsMax Age: 70 Years

Plain Language Summary

Simplified for easier understanding

This study is testing a new type of CAR-T cell therapy for relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) — a type of blood cancer that has come back or stopped responding to treatment. This therapy uses specially modified immune cells with two additional gene edits (BCOR and ZC3H12 knocked out) designed to make the CAR-T cells more effective and longer-lasting. **You may be eligible if...** - You are between 18 and 70 years old - You have CD19-positive B-ALL that has relapsed (come back) or is refractory (not responding to treatment) - Your cancer has relapsed at least twice, or relapsed after a stem cell transplant, or did not respond to two rounds of standard chemotherapy - Your overall health is adequate (ECOG ≤ 2) - Your heart, kidney, and liver function meet required levels **You may NOT be eligible if...** - Your cancer does not express CD19 - You have not exhausted other available treatment options - You are pregnant or breastfeeding - Your organ function does not meet required thresholds - You have active uncontrolled infection or other serious medical conditions 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.