PD1-CD19-CART in Patients With r/r B-cell Lymphoma

PD1-CD19-CART is a kind of chimeric antigen T cell targeting CD19 with both CD19-CAR gene integration and also PD1 knockout by one-step gene-editing. After completion of study treatment, subject participation for this study will be followed up to 15 years post T cell infusion.

Inclusion criteria

• Have the capacity to give informed consent;
• ALL patients with the age between 18 and 70 years old;
• Expected survival >3 moths;
• With no severe heart and lung disease;
• Previously confirmed diagnosis as CD19+ NHL within 6 months;
• Hematological index as following, white blood cell (WBC)≥1.5×10^9/L，absolute neutrophil count (ANC) ≥0.8×10^9/L, Platelet count≥50×109/L, Hemoglobin (Hgb) ≥ 90mg/L, lymphocyte count≥ 0.4×10^9/L；
• Blood biochemical index as no more than 1.5* ULN, including total bilirubin (TBIL), transglutaminase (AST), alanine aminotransferase (AST), Creatinine (SCr), Urea in patients with no tumor metastasis in liver and kidney; Blood biochemical index no more than 5* ULN in patients with tumor metastasis in liver and kidney;
• With a stable cardiac function, the left ventricular ejection fraction (LVEF) ≥ 55%;
• Virological tests were negative for EBV, CMV, HIV, TP and HCV; a negative HBV DNA test is acceptable if HBsAg is positive;
• ECOG <2;
• Relapsed or refractory (r/r) NHL including, Diffuse large B cell lymphoma(DLBCL, NOS), stage Ⅲ-Ⅳ;Primary mediastinal large B-cell lymphoma (PMBL), stage Ⅲ-Ⅳ; High grade B-cell lymphoma (HGBL), stage Ⅲ-Ⅳ; Mantle cell lymphoma (MCL), stage Ⅲ-Ⅳ; follicular lymphoma (FL), stage Ⅲ-Ⅳ and with aggression. r/r NHL defined as following, demonstrate disease that persists or relapse after achieving complete response (CR) after > 2 cycles of standard chemotherapy, or relapse after autologous hematopoietic stem cell transplantation (auto-HSCT), or not achieving CR after auto-HSCT.

Exclusion criteria

• Pregnant or lactating women;
• With a pregnancy plan in the next 2 years;
• Prior treatment of anti-GVHD therapy;
• Acceptance of allogeneic stem cell transplant (ASCT);
• Isolated extramedullary relapse of ALL;
• Severe mental disorders, active autoimmune diseases, active infectious diseases, severe cardiovascular diseases;
• Partial prothrombin time or activated partial thromboplastin time or international standardized ratio > 1.5*ULN without anticoagulant treatment;
• History of other type of maligant tumors;
• Any circumstances that possibly increase the risk of subjects or interfere with study results, which judged by investigator.