car-t following asct for relapsed/refractory b-cell non-hodgkin's lymphoma (r/r b-nhl) with high-risk prognostic factors

Conditions: B-cell Non Hodgkin Lymphoma

Summary: clinical trial for the safety and efficacy of cd19 car-t following autologous hematopoietic stem cell transplantation (asct) for relapsed/refractory b-cell non-hodgkin's lymphoma (r/r b-nhl) with high-risk prognostic factors

this is a single-center, single-arm, open-label, prospective clinical trial to evaluate the efficacy and safety of relmacabtagene autoleucel (relma-cel) infusion following high-dose chemotherapy and autologous stem-cell transplantation (hdt/asct) in relapsed or refractory b-cell non-hodgkin's lymphoma patients with high-risk prognostic factors (extranodal involvement/bulky mass ≥5 cm in diameter/tp53 alterations). relma-cel will be infused on day +3 (±1d) with a fixed dose of 100x10\^6. the study will assess the safety and efficacy of this combinational therapy, including the investigators assessed the best complete response rate (bcr) in 3 months (primary endpoint), objective response rates, survivals, incidence and severity of cytokine release syndrome (crs), immune effector cell-associated neurotoxicity syndrome (icans), hematological, and other non-hematological toxicities of the subjects.

Eligibility criteria:
inclusion criteria: 1. histologically confirmed b-cell non-hodgkin's lymphoma including the following types * diffuse large b-cell lymphoma * high-grade b-cell lymphoma with or without myc and blc2 and/or bcl6 rearrangement * transformed lymphoma * primary mediastinal large b-cell lymphoma * follicular lymphoma (fl) 2. relapsed or refractory diseases fulfilling one of the following criteria (individuals must have received anti-cd20 monoclonal antibody and anthracycline-containing chemotherapy regimen) * primary refractory disease, defined as disease progression after first-line immunochemotherapy or disease progression within 6 weeks of the end of the last chemotherapy * stable disease (sd) as best response after at least 4 cycles of first-line therapy * partial response (pr) as best response after at least 6 cycles of first-line therapy (biopsy-proven residual disease is needed for individuals with deauville score of 4) * pr as best response after at least 2 cycles of second-line therapy * disease relapse ≤12 months after the completion of first-line immunochemotherapy * relapsed or refractory disease after ≥2 lines of chemotherapy 3. presence of at least one of the following high-risk prognostic factors: (1) extranodal involvement; (2) maximum diameter of the bulky mass ≥5 cm; (3) tp53 gene alterations 4. eastern cooperative oncology group (ecog) performance status of 0-2 5. eligible for hdct/asct based on the investigator's assessment and are scheduled to undergo an asct sequential car-t treatment regimen 6. adequate renal and hepatic function defined as: * serum alanine aminotransferase (alt/ast) ≤ 3 upper limit of normal (uln) * total bilirubin ≤1.5 mg/dl(\<3 times uln in patients with gilbert's syndrome, cholestasis due to hepatoportal compression adenopathy, biliary obstruction in patients with liver involvement or lymphoma) * serum creatinine ≤1.5 uln, or creatinine clearance (as estimated by cockcroft gault) ≥ 30 ml/min 7. cardiac ejection fraction ≥ 40% 8. baseline oxygen saturation \> 95% on room air 9. life expectancy ≥3 months exclusion criteria: 1. history of autologous or allogeneic stem cell transplantation 2. active hbv or hcv infection, defined as hbv-dna or hcv-dna levels above the normal upper limit, with or without abnormal liver function. individuals with positive hbsag or hbcab should receive antiviral prophylaxis for at least 12 months after car-t cells infusion. 3. presence of uncontrolled infection, cardio-cerebrovascular disease，coagulopathy, or connective tissue disease. 4. history of hiv infection 5. prior chimeric antigen receptor cellular immunotherapy targeting cd19 6. pregnant or lactating patients