A Prospective, Single - Arm Clinical Study on the Safety and Efficacy of Early Second Infusion of CD19 CAR - T Based on ctDNA Monitoring in the Treatment of Relapsed/Refractory Large B - Cell Lymphoma
The goal of this clinical trial is to evaluate the efficacy and safety of early secondary infusion of CD19 CAR T-cell therapy in adults with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), guided by ctDNA monitoring. The main questions it aims to answer are: 1. Efficacy: Does early secondary CAR-T infusion improve the 3-month complete remission (CR) rate and long-term survival outcomes (e.g., 1-year PFS, OS)? 2. Safety: What are the adverse events associated with secondary CAR-T infusion, such as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity (ICANS), and infections? This is a single-arm, single-center, prospective study. All participants will receive: * Leukapheresis to collect T cells for CAR-T manufacturing. * Preconditioning chemotherapy (fludarabine and cyclophosphamide) to prepare the body for CAR-T infusion. * Two CD19 CAR-T infusions: The first infusion (2×10⁶ cells/kg) followed by a second infusion (same dose) if ctDNA remains positive when PET/CT shows CR or PET/CT shows PR within 60 days post-first infusion. Participants will undergo: * Frequent hospital monitoring for ≥14 days post-infusion to manage potential toxicities. * Regular follow-ups (e.g., blood tests, ctDNA analysis, PET/CT scans) at scheduled intervals up to 12 months. * Continuous safety assessments, including CRS grading, neurological evaluations, and infection monitoring.
• Age ≥18 years, regardless of gender.
• Life expectancy \>12 weeks.
• ECOG performance status 0-2.
• Histologically or cytologically confirmed B-cell non-Hodgkin lymphoma per WHO 2016 classification, including:
• Diffuse large B-cell lymphoma (DLBCL) Primary mediastinal large B-cell lymphoma (PMBCL) Transformed follicular lymphoma (TFL) High-grade B-cell lymphoma (HGBCL).
• Relapsed/refractory disease, defined as:
• ≥1 prior relapse, Failure to achieve partial response (PR) after 2-3 cycles of first-line therapy, Failure to achieve complete response (CR) after 4-6 cycles of first-line therapy, Primary refractory disease, Secondary refractory disease, Disease progression following last line of therapy.
• Adequate venous access for leukapheresis, with:
• Hemoglobin ≥80 g/L, Absolute neutrophil count ≥1.0 ×10⁹/L, Platelet count ≥75 ×10⁹/L, OR parameters not meeting above thresholds but deemed acceptable for mononuclear cell collection per investigator's judgment.
• ≥1 measurable lesion per Lugano 2014 response criteria.
• Organ function requirements:
• Renal: Serum creatinine ≤2×ULN OR creatinine clearance ≥40 mL/min (Cockcroft-Gault formula).
• Cardiopulmonary:
• Left ventricular ejection fraction (LVEF) \>50%, Baseline oxygen saturation \>92% on room air.
• Hepatic:
• Total bilirubin ≤2×ULN (≤5×ULN in Gilbert syndrome), ALT/AST ≤3×ULN (≤5×ULN in patients with hepatic involvement).
• Negative serum pregnancy test for women of childbearing potential (WOCBP). Postmenopausal (≥2 years since last menses) or surgically sterilized women are exempt.
⁃ Within 60 days post-axi-cel:
‣ Persistent ctDNA(+) or ctDNA(-→+) under CR or PET/CT-confirmed PR