A Multiple Center Study on NOXA Expression-guided Randomized Chidamide Bridging Intervention in CAR-T Treated NHL Patients
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.
• Age 16-75, male or female;
• 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);
• Eastern Cooperative Oncology Group (ECOG) physical status is 0-3;
• Life expectancy ≥12 weeks;
• 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;
• There are measurable target lesions;
• CD19 positive;
• 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
• 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.