exploratory clinical study of cd19-targeted car-t and car-dc in the treatment of relapsed and refractory b-cell lymphoma

Conditions: Relapsed and Refractory B-cell Lymphoma

Summary: this is an open, single-arm, prospective, dose-escalation clinical trial designed to evaluate the safety and the preliminary efficacy of cd19-targeted car-t combined with car-dc in the treatment of relapsed and refractory b-cell lymphoma

6-18 patients are planned to be enrolled in the dose-escalation trial. the dose of cd19-car-dc was according to the 3+3 dose-escalation principle (0.25×10\^6/kg, 0.5×10\^6/kg, 0.75×10\^6/kg ( ±20%) . car-t was 2×10\^6/kg . the primary endpoints are dlt, mtd, and the second endpionts are the overall response rates (cr and pr), overall survival, and progression-free survival. based on the results in the dose-escalation trial, the recommended dose will be determined. another 52 patients will be enrolled to continue estimating the safety and efficacy.

Eligibility criteria:
inclusion criteria: 1. male or female participants aged 18 to 75 years old at the time enrollment, with ecog score of ≤ 3; 2. patients should provide a written informed consent; 3. histologically confirmed cd19+ dlbcl, hgbl-dhl, mcl, tfl, pmbl; * confirmation obtained from central pathology review before enrollment; * sufficient formalin-fixed, paraffin-embedded tumor samples were required for histologically confirmed diagnosis and detection of cd19 expression; * relapsed dlbcl and tfl after ≥2 lines of chemotherapy that include rituximab and anthracycline, or refractory disease as defined in the scholar-1 study: progressive disease after receiving ≥ 4 cycles of first-line therapy or stable disease (received 2 cycles of later-line therapy) as best response to chemotherapy or relapse ≤ 12 months after autologous stem cell transplantation (asct); * relapsed/refractory mcl after ≥ 2 lines of prior therapy, including immunochemotheapy and btk inhibitor such as ibrutinib, or patient did not agree to receive btk inhibitor treatment; * at least one measurable tumor according to revised international working group (iwg) response criteria; 4. life expectancy ≥ 3 months; 5. adequate cardiac, pulmonary, liver, renal, and bone marrow functions, with the following laboratory values: an absolute neutrophil count \> 1,000/mm3, platelets count ≥ 45,000/mm3, and hemoglobin \> 8.0g/dl; alanine aminotransferase and aspartate aminotransferase ≤ 2.5 × the upper limit of the normal range (uln), and total bilirubin ≤ 2.0 mg/dl; a serum creatinine of ≤ 1.5 × uln; a left ventricular ejection fraction ≥ 50%; exclusion criteria: 1. prior treatment that included anti-cd19-targeted therapy, car t cell therapy, gene therapy, and allogenic hematopoietic stem cell transplantation (allo-hsct); 2. chemotherapy other than lymphodepleting chemotherapy, therapeutic doses of steroids, immunosuppressive agent, any radiation therapy or anti-tumor targeted therapy including lenalidomide, bortezomib, ibrutinib, received within 2 weeks before cell collection; 3. clinical trial with investigational drug was performed within 4 weeks; 4. history of other cancers; 5. active hepatitis b or hepatitis c. hepatitis b: hbv-dna ≥ 1,000 iu/ml; hepatitis c: hcv rna positive; 6. hiv infection; 7. uncontrollable infection of active bacteria and fungi; 8. currently pregnant or refusal to practice birth control within 1 year; 9. active autoimmune or inflammatory diseases; 10. central nervous system lymphoma.