cd19 car-t expressing il-7 and ccl19 combined with anti-pd1 in rr-dlbcl

Conditions: Diffuse Large B-cell Lymphoma

Summary: the goal of this clinical trial is to test cd19-7×19 car-t cells combined with tislelizumab in refractory and relapsed diffuse large b lymphoma. the main question\[s\] it aims to answer are: question 1：what is the safety of cd19-7×19 car-t cells combined with tislelizumab in the treatment of relapsed or refractory diffuse large b-cell lymphoma. question 2：what is the efficacy of cd19-7×19 car-t cells combined with tislelizumab in the treatment of relapsed or refractory diffuse large b-cell lymphoma. participants will be asked to receive clinical evaluation before car-t, including physical examination, blood routine test, biochemical test, imaging test, etc.peripheral blood lymphocytes will be collected for preparation of car-t cells after enrollment. pretreatment chemotherapy with fludarabine and cyclophosphamide will be used before car-t infusion. on the 31st day after car-t infusion, tislelizumab 200mg was given once every 21 days for 6 cycles. participants will be required to report concomitant medication and adverse events, and their disease was evaluated throughout the study.


Eligibility criteria:
inclusion criteria: 1. age ≥ 18, upper limit 75, male or female; 2. ecog score 0-3; 3. histologically confirmed diffuse large b-cell lymphoma (dlbcl) \[diagnostic criteria according to who 2008\]; 4. cd19 positive (immunohistochemistry or flow cytometry). 5. dlbcl refractory or relapse is defined as: complete remission is not achieved after 2-line treatment; let what disease progress occurs during treatment, or the disease stability time is equal to or less than 6 months; or autologous hematopoietic stem disease progression or recurrence within 12 months after cell transplantation; 6. previous treatment for patients with diffuse large b cell lymphoma must include rituximab (cd20 monoclonal antibody) and anthracyclines; 7. at least one measurable lesion is required, and any lymph node lesion with a length greater than 1.5cm or extranodal lesion is required if any length diameter is greater than 1.0 cm, the lesions on pet-ct scan have uptake (suv is larger than liver blood pool); 8. absolute value of peripheral blood neutrophils ≥ 1000/ μ l. platelets ≥ 45000/ μ l 9. heart, liver and kidney functions: creatinine \< 1.5mg/dl; alt/ast less than 2.5 times of normal upper limit; total bilirubin \< 1.5mg/dl; cardiac ejection fraction (ef) ≥ 50%; 10. have sufficient understanding and voluntarily sign the informed consent form; 11. people with fertility must be willing to use contraceptive methods; 12. according to the judgment of the researcher, the expected survival period is at least 4 months; 13. willing to follow the visit schedule, administration plan, laboratory inspection and other test steps. exclusion criteria: 1. have a history of other tumors; 2. autologous hematopoietic stem cell transplantation was performed within 6 weeks; 3. any target car-t treatment was performed within 3 months before this car-t treatment; 4. previously used any commercially available pd-1 monoclonal antibody; 5. cytotoxic drugs, glucocorticoids and other targeted drugs were received within 2 weeks before cell collection; 6. active autoimmune diseases; 7. uncontrollable active bacterial and fungal infections; 8. hiv infection and syphilis infection; active hepatitis b or hepatitis c: hepatitis b: hbv-dna ≥ 1000 iu/ml; hepatitis c: hcv rna is positive and liver function is abnormal. 9. known central nervous system lymphoma.