RecruitingPhase 1Phase 2NCT05370547

Chidamide Bridging for CAR-T Therapy

A Multiple Center Study on NOXA Expression-guided Randomized Chidamide Bridging Intervention in CAR-T Treated NHL Patients


Sponsor

Chinese PLA General Hospital

Enrollment

120 participants

Start Date

May 25, 2022

Study Type

INTERVENTIONAL

Conditions

Summary

The previous research suggests that the low expression of NOXA protein may be an important biomarker for the treatment of drug resistance of chimeric antigen receptor-T (CAR-T) cells. Up regulating the expression of NOXA through histone deacetylase inhibitor (HDACi) can improve drug resistance and significantly improve the therapeutic effect of CAR-T cells. This study will enroll approximately 120 subjects with recurrent or refractory (r/r) B-cell non-Hodgkin's lymphoma (NHL). Those with high expression of NOXA will receive conventional CAR-T treatment (without chidamide bridging), and those with low expression of NOXA will be randomly assigned 1:1 to those without or containing chidamide bridging. The purpose of this study was to evaluate the clinical response and safety of chidamide bridging.


Eligibility

Min Age: 16 YearsMax Age: 75 Years

Plain Language Summary

Simplified for easier understanding

This study is testing whether adding a drug called chidamide (an oral drug that changes how cancer genes are expressed) before CAR-T cell therapy improves outcomes for people with relapsed or treatment-resistant large B-cell lymphoma, follicular lymphoma, or mantle cell lymphoma. The goal is to make the CAR-T therapy work better. **You may be eligible if...** - You are 16–75 years old - You have relapsed or refractory large B-cell lymphoma, follicular lymphoma (grade 1–3a), or mantle cell lymphoma - Your cancer has failed at least 2 prior treatment lines including an anti-CD20 drug and anthracycline - Your cancer cells test positive for CD19 - You are in reasonably good health (ECOG 0–3) - Your organ function is adequate **You may NOT be eligible if...** - You are allergic to chidamide - Your cancer has spread to the brain - You have HIV or uncontrolled viral infection (hepatitis B or C) - You have serious heart problems (heart failure, recent MI, or arrhythmia) - You have had a stroke or brain bleed in the past 3 months - You are pregnant or breastfeeding - You cannot swallow oral medications 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

DRUGChidamide

1. Chidamide monotherapy mode: Chidamide was administered for at least 6 times after leukapheresis, 10mg oral D1-4, 20mg oral D7 every 3 days to the beginning day of FC conditioning. 2. Chidamide combination mode: The combination of one or more of the following drugs in addition to chidamide is permitted: glucocorticoids, BTK inhibitors, chemotherapy, other previously used resistance drugs, etc.

DRUGFludarabine and cyclophosphamide

Patients should be received FC regimen conditioning 3 to 5 days prior to CAR-T cell infusion. The recommended regimen is intravenous fludarabine (25-30 mg/m\^2) and cyclophosphamide (250-500 mg/m\^2) daily for 3 consecutive days. The clinician may also adjust the cleansing regimen according to the patient's actual situation.

BIOLOGICALAnti-CD19 CAR-T cells

A single infusion of CAR-transduced autologous T cells administered intravenously at a target dose of 100 × 10\^6 for Relma-cel or 2 × 10\^6/kg for Axi-cel. Other commercial CAR-T doses are determined by specific drug infusion instructions. The dose of experimental CAR-T was determined by the investigator. Infusion volume was calculated based on CAR-T cell density and recommended dose.


Locations(13)

The First Affiliated Hospital of Soochow University

Suzhou, Suzhou, China

Tianjin Medical University Cancer Institute and Hospital

Tianjin, Tianjin Municipality, China

West China Hospital of Sichuan University

Chengdu, Sichuan, China

Sun Yat-Sen University Cancer Hospital

Guangzhou, Guangzhou, China

Tongji Hospital, Tongji Medical College of HUST

Wuhan, Hubei, China

Xiehe Hospital, Tongji Medical College of HUST

Wuhan, Hubei, China

Tongji Hospital of Tongji University

Shanghai, Shanghai Municipality, China

Biotherapeutic Department, Chinese PLA General Hospital

Beijing, China

The First Affiliated Hospital of Zhejiang University

Hangzhou, Zhejiang, China

Zhujiang Hospital of Southern Medical University

Guangzhou, Guangdong, China

Beijing Tongren Hospital, Capital Medical University

Beijing, Beijing Municipality, China

Peking Union Medical College Hospital

Beijing, Beijing Municipality, China

Peking University Cancer Hospital

Beijing, Beijing Municipality, China

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NCT05370547


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