Relmacabtagene autoleucel（自体干细胞）治疗非霍奇金淋巴瘤：II 期临床试验

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

主要终点：Best Complete Response (CR) Rate in 3 months · Best Complete Response rate in 3 months is defined as the incidence of subjects achieving complete remission (CR) within 3 months after CAR-T infusion according to the Lugano Classification (Cheson et al, 2014), as determined by study investigators. · 3months post CAR-T infusion
次要终点：Objective remission rate (ORR) in 3months；Duration of Response (DOR)；Progression-Free Survival (PFS)；Overall Survival (OS)；Adverse Events rate as assessed by CTCAE version 5.0

• CAR-T following ASCT · EXPERIMENTAL · Participants will receive high-dose chemotherapy followed by stem-cell infusion, and a fixed dose of CAR-T cells will be infused.

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