Multicenter, Single-Arm Exploratory Phase I Clinical Study (Assessment of Safety and Efficacy) of Fully Human BAFF-R Chimeric Antigen Receptor T-Cell Injection in Relapsed/Refractory BAFF-R-Positive B-Cell Lymphoma

This is an investigator-initiated dose-escalation clinical study. Its primary objectives are to evaluate the safety of BAFF-R CAR-T in participants with relapsed/refractory BAFF-R-positive B-cell lymphoma and explore the Maximum Tolerated Dose (MTD) of BAFF-R CAR-T for this patient population. Additionally, the study will investigate the efficacy and pharmacokinetic characteristics of BAFF-R CAR-T in these participants.

To evaluate the safety and preliminary dose range of BAFF-R CAR-T in participants with relapsed/refractory BAFF-R-positive B-cell lymphoma, the dose groups of this trial are as follows:Dose Group 1: 1 × 10⁶ CAR⁺ T Cells/kg, Dose Group 2: 2 × 10⁶ CAR⁺ T Cells/kg, Dose Group 3: 3 × 10⁶ CAR⁺ T Cells/kg.The dose design of this study refers to the "3+3" dose escalation design for the first-in-human (FIH) trial of new drugs.

For each dose group, there must be a 14-day interval after the first participant completes BAFF-R CAR-T infusion before subsequent participants can receive BAFF-R CAR-T infusion.

If 2 cases of Dose-Limiting Toxicity (DLT) occur in the Dose 1 group, the investigators will decide whether to explore a lower dose group.

After the completion of the dose escalation phase, a decision on whether to proceed with the dose expansion phase and the determination of the dose for this phase will be made based on safety and Pharmacokinetic (PK) data.

In the dose expansion phase, after the completion of the dose escalation phase, the investigators will first identify the optimal dose group based on the available data, including preliminary efficacy and/or PK data. Subsequently, additional participants may be enrolled to receive cell infusion until the sample size reaches 20 cases. This is to further evaluate the tolerability, safety, and efficacy of the BAFF-R CAR-T cell injection.

The study process includes the screening period, apheresis period, baseline and chemotherapy preconditioning period, BAFF-R CAR-T infusion period, and post-infusion follow-up period for safety and efficacy.

After signing the Informed Consent Form (ICF), participants undergo screening examinations. Those who meet the enrollment criteria receive peripheral blood mononuclear cell (PBMC) apheresis, which is used for BAFF-R CAR-T preparation. The cell preparation takes 15 to 25 days. Participants receive lymphodepleting preconditioning 4 to 2 days before BAFF-R CAR-T infusion (Day 0) and complete the baseline assessment. BAFF-R CAR-T is administered via intravenous infusion as a single dose. After BAFF-R CAR-T infusion, follow-up for safety and efficacy is conducted. The follow-up content includes physical examinations, vital signs monitoring, laboratory tests, imaging examinations, and treatment efficacy evaluation.