Using Chidamide to Enhance CAR-T Therapy for Non-Hodgkin's Lymphoma

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

This study is testing if adding a drug called chidamide can make CAR-T therapy work better for people with tough-to-treat B-cell non-Hodgkin's lymphoma.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 120 (estimated)
• Ages: 16 Years to 75 Years
• Sex: All
• Sponsor: Chinese PLA General Hospital (other)
• Drugs / interventions: doxorubicin, CAR-T, chimeric antigen receptor, CAR T, chemotherapy, cyclophosphamide, fludarabine
• Locations: 13 sites (Beijing, Beijing and 12 other locations)
• Trial ID: NCT05370547 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the use of chidamide, a histone deacetylase inhibitor, to improve the effectiveness of CAR-T cell therapy in patients with recurrent or refractory B-cell non-Hodgkin's lymphoma. The study will enroll approximately 120 participants, assessing their NOXA protein expression levels to determine eligibility for chidamide bridging. Patients with low NOXA expression will be randomly assigned to receive either chidamide bridging or standard CAR-T treatment. The primary goal is to evaluate the clinical response and safety of this combined approach.

Who should consider this trial

Good fit: Ideal candidates are individuals aged 16-75 with recurrent or refractory large B-cell lymphoma or related conditions.

Not a fit: Patients with high NOXA expression or those who do not meet the eligibility criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly enhance the therapeutic outcomes for patients with drug-resistant non-Hodgkin's lymphoma.

How similar studies have performed: Previous studies have indicated that targeting NOXA expression may improve CAR-T therapy outcomes, suggesting potential success for this approach.

Eligibility criteria

Inclusion Criteria:

1. Age 16-75, male or female;
2. Recurrent or refractory large B-cell lymphoma (LBCL) ,grade 1-3a follicular lymphoma (FL) and mantle cell lymphoma (MCL). Recurrent or refractory disease was defined as progression after systemic treatment with second-line or more lines (including CD20 monoclonal antibody and doxorubicin) or primary resistance (disease progression during first-line treatment or within 6 months after completion of treatment). LBCL includes diffuse large B-cell lymphoma non-specific type (DLBCL-NOS), diffuse large B-cell lymphoma transformed by follicular lymphoma (TFL), grade 3b FL, primary mediastinal large B-cell lymphoma (PMBCL), high-grade B-cell lymphoma with MYC and Bcl-2 and/or Bcl-6 rearrangement ( double strike/triple hit lymphoma, DHL/THL);
3. Eastern Cooperative Oncology Group (ECOG) physical status is 0-3;
4. Life expectancy ≥12 weeks;
5. Subjects must be willing to undergo either excised or large-needle lymph node or tissue biopsy, or provide lymph node or tissue biopsy from the most recent available archived tissue for immunohistochemical NOXA testing and pathology review in the study center laboratory;
6. There are measurable target lesions;
7. CD19 positive;
8. Are willing to use contraception according to the following criteria:

   A. Women of reproductive age (15-49 years) must undergo a pregnancy test with negative results within 7 days before starting treatment; B. Women of reproductive age should use effective contraception for at least 120 days after the last dose of the study drug (contraceptive success rate of at least 99%). The subject should communicate with the available contraceptive methods with at least 99% success rate and confirm the understanding of the period; C. Male subjects used effective contraception for at least 93 days after the last dose of study drug (contraceptive success rate of at least 99%). The subject should communicate with the available contraceptive methods with at least 99% success rate and confirm the understanding of the period; D. Infertile women (i.e., surgically sterilized by hysterectomy and/or bilateral oophorectomy or amenorrhea ≥12 months and age \> 45 years) are not subject to conditions A and B above
9. Adequate bone marrow and organ functions (normal values shall not be obtained with growth factors, and hemocytopenia caused by lymphoma invasion of bone marrow is not subject to conditions A, B, and C below) :

A. Neutrophil count (ANC) ≥1.0×10\^9/L; B. Hemoglobin ≥8.0g/dL; C. Platelet count ≥50×10\^9/L; D. Total bilirubin ≤1.5× upper limit of normal value (ULN) (\< 3 TIMES ULN for patients with Gilbert syndrome, cholestasis caused by hilar compression adenosis, biliary obstruction caused by liver involvement or lymphoma); E. Alanine aminotransferase/aspartate aminotransferase (ALT/AST) ≤2.5×ULN or ≤5×ULN when liver invasion is present; F. Creatinine clearance ≥40ml/min using the cockcroft-gault equation or glomerular filtration rate ≥40ml/min/1.73m2 using the modified renal disease diet formula; G. Lipase ≤1.5×ULN.

Exclusion Criteria:

1. Patients known to be allergic to the drug Chidamide;
2. Lymphoma involves the central nervous system;
3. Known human immunodeficiency virus (HIV) infection or immunopositive test;
4. Viral infections that cannot be controlled by antiviral drugs, such as herpetic virus infection, acute or chronic active hepatitis B, acute or chronic active hepatitis C, etc. \[Note: chronic hepatitis B virus (HBV) carriers or non-active hepatitis B surface antigen (HBsAg) positive subjects and HBV-DNA lower than the detection limit can be included in the group; hepatitis C virus (HCV) antibody negative can be enrolled, HCV antibody positive patients need to be tested for HCV-RNA, if negative can be enrolled\];
5. Presence of active infectious disease requiring treatment;
6. Received live vaccine within 30 days prior to enrollment;
7. Active autoimmune disease requiring systemic treatment within 12 months prior to enrollment (i.e., disease-modifying drugs, corticosteroids, or immunosuppressive drugs). Note: Alternative therapies (such as thyroxine, insulin, or physiologic corticosteroid replacement for adrenal or pituitary dysfunction) are not considered a systemic treatment;
8. History of severe allergic reactions;
9. Presence of congestive heart failure or uncontrolled arrhythmias classified by the New York Heart Association as class III-IV;
10. Patients with clinically significant electrocardiogram abnormalities and potential risk of malignant arrhythmias;
11. Clinically significant cardiac events, including unstable angina, acute myocardial infarction, and/or cardiac transmission problems, occurred within 6 months prior to enrollment;
12. A history of stroke or intracranial hemorrhage within 3 months prior to enrollment;
13. Major surgery or trauma occurred within 28 days prior to enrollment, or major side effects have not been recovered;
14. Accompanied by uncontrolled major medical conditions, including, but not limited to, kidney, liver, blood, gastrointestinal, endocrine, pulmonary, neurological, brain or psychiatric disorders;
15. Current or previous malignancy within 3 years prior to enrollment, excluding cured basal or squamous cell skin cancer, superficial bladder cancer, prostatic intraepithelial tumor and carcinoma in situ of the cervix;
16. Conditions in which a known mental or physical illness interferes with cooperation with the requirements of the study or disrupts the results or interpretation of the results and, in the opinion of the therapeutic investigator, makes the patient unfit for study participation;
17. There is the situation that the researcher's judgment will interfere with the whole study participation; Situations where there is significant risk to the subject; Or interferes with the interpretation of research data;
18. Pregnant or breast-feeding patients;
19. Inability to swallow and retain oral medications, malabsorption syndrome, diseases that significantly affect gastrointestinal function, total resection of the stomach or small intestine, ulcerative colitis, symptomatic inflammatory bowel disease, partial or complete intestinal obstruction;
20. Inability to understand or unwillingness to sign informed consent.

Where this trial is running

Beijing, Beijing and 12 other locations

• Beijing Tongren Hospital, Capital Medical University — Beijing, Beijing, China (RECRUITING)
• Peking Union Medical College Hospital — Beijing, Beijing, China (RECRUITING)
• Peking University Cancer Hospital — Beijing, Beijing, China (RECRUITING)
• Zhujiang Hospital of Southern Medical University — Guangzhou, Guangdong, China (RECRUITING)
• Sun Yat-Sen University Cancer Hospital — Guangzhou, Guangzhou, China (RECRUITING)
• Tongji Hospital, Tongji Medical College of HUST — Wuhan, Hubei, China (RECRUITING)
• Xiehe Hospital, Tongji Medical College of HUST — Wuhan, Hubei, China (RECRUITING)
• Tongji Hospital of Tongji University — Shanghai, Shanghai, China (RECRUITING)
• West China Hospital of Sichuan University — Chengdu, Sichuan, China (RECRUITING)
• The First Affiliated Hospital of Soochow University — Suzhou, Suzhou, China (RECRUITING)
• Tianjin Medical University Cancer Institute and Hospital — Tianjin, Tianjin, China (RECRUITING)
• The First Affiliated Hospital of Zhejiang University — Hangzhou, Zhejiang, China (RECRUITING)
• Biotherapeutic Department, Chinese PLA General Hospital — Beijing, China (RECRUITING)

Study contacts

• Principal investigator: Weidong Han, Ph.D — Biotherapeutic Department, Chinese PLA General Hospital
• Study coordinator: Weidong Han, Ph.D

Conditions: Non Hodgkin's Lymphoma, CAR-T, NOXA, Chidamide