Safety and Efficacy of Metabolically Armed CD19 CAR-T Cells (Meta10-19) in the Treatment of r/r DLBCL Clinical Research

Inclusion Criteria

• •1. The patient or his/her guardian voluntarily signed the informed consent;
• •2. Adult Patients with relapsed and refractory diffuse large B-cell lymphoma (Primary mediastinal large B-cell lymphoma and transformed follicular lymphoma are included)
• •Definition of refractory:
• •1. No response to the last treatment, including:
• •The best response to the last treatment was PD, or ; The best response to the last treatment was SD and the duration was not more than 6 months after the last dose.
• •2. Not suitable for autologous hematopoietic stem cell transplantation (ASCT), or ASCT refractory, including:
• •Disease progression or recurrence within 12 months or less (recurrence must be confirmed by biopsy) after ASCT treatment, or; Patients accept remedial treatment after ASCT must have no response or relapse after the last treatment.
• •3. Patients who had previously received ≥2 lines therapy including at least:
• •1. A chemotherapy regimen containing anthracyclines；
• •2. For patients with transformed DLBCL from follicular lymphoma, they must have previously received chemotherapy for follicular lymphoma and have refractory disease after transformation to DLBCL.
• •4. CD19 expression was positive by immunohistochemistry or flow cytometry (accept the results of this peripheral blood mononuclear cells or previous report from a Class A tertiary hospital before peripheral blood collection)
• •5. At least one measurable lesion at baseline, according to the initial assessment, staging and Response Assessment recommendations for Hodgkin's and non-Hodgkin's lymphoma (2014 edition)
• •6. Expected survival time greater than 12 weeks
• •7. The baseline ECOG score was 0 or 1
• •8. organ function：
• •1. Kidney function is defined as:
• •Serum creatinine ≤1.5 times ULN, or； The glomerular filtration rate (eGFR) estimated by MDRD formula was ≥60m/min/1.73m2；\[eGFR=186×（age）-0.203×SCr-1.154（mg/dl），for females, the result was ×0.742\]；
• •2. Liver function is defined as： ALT≤5 times ULN, and; Patients with total bilirubin ≤2.0mg/dl, except those with Gilbert-Meulengracht syndrome. Patients with Gilbert-.Meulengracht syndrome with total bilirubin ≤3.0 times ULN and direct bilirubin ≤1.5 times ULN were included.
• •3. Pulmonary function: ≤CTCAE grade 1 dyspnea and oxygen saturation of blood (SaO2) ≥91% in indoor air environment.
• •9. Hemodynamic stability was determined by echocardiography or multichannel radionuclide angiography (MUGA) and LVEF ≥45％
• •10. Patients using the following drugs must meet the following conditions:
• •1. Steroid: Therapeutic doses of steroids must be discontinued 2 weeks prior to Meta10-19 infusion. However, physiological replacement doses of steroids are permitted, hydrocortisone or its equivalent \< 6-12mg/mm2/ day；
• •2. Immunosuppressive agent: Any immunosuppressive drug must be stopped ≥4 weeks before the informed consent is signed
• •3. Anti-proliferative therapy in addition to preconditioning chemotherapy 2 weeks prior to Meta10-19 infusion
• •4. Treatment for CNS disease must be stopped 1 week before Meta10-19 infusion (e.g., intrathecal methotrexate)
• •11. The patient has recovered from the toxicity of the previous treatment, that is, the CTCAE toxicity grade is less than 1 (The exception is specific toxicity of grade 2 or less, such as hair loss, which the researchers have determined is not recoverable in a short period of time) is suitable for pretreatment chemotherapy and CAR T cell therapy
• •12. Women of childbearing age and all male patients must consent to use a effective contraception for at least 12 months after Meta10-19 infusion and until two consecutive PCR tests show no more CAR T cells in vivo；