NCT06902012

Safety and Efficacy of Early Second Infusion of Axi-cel Based on ctDNA for R/R Large B - Cell Lymphoma

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

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 15 (estimated)
• Sponsor: Zhujiang Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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. Researchers will enroll 15 eligible participants who have failed prior therapies. 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 or PET/CT shows incomplete response 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. Key outcomes include 3-month CR rate, objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and incidence of severe adverse events. This trial aims to optimize CAR-T therapy by leveraging ctDNA-guided early intervention to enhance long-term remission in high-risk DLBCL patients.

Conditions

• Relapsed/Refractory Diffuse Large B-cell Lymphoma

Interventions

Type	Name	Description
DRUG	Infusion of Axicabtagene Ciloleucel	Drug: Axicabtagene Ciloleucel (CD19 CAR-T cells), 2×106 cells/kg, IV infusion at Day 0 and 30-90 days post-first infusion. Drug: Cyclophosphamide (500 mg/m²) + Fludarabine (30 mg/m²), IV on Days -5, -4, -3. Procedure: ctDNA monitoring via liquid biopsy at pre-lymphodepletion and Months 1, 2, 3, 6, 9, 12 post-infusion.

Timeline

• Start date: 2027-02-01
• Primary completion: 2028-02-01
• Completion: 2028-08-01
• First posted: 2025-03-30
• Last updated: 2025-03-30

Locations

1 site across 1 country: China