NCT07259070

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

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

• Status: Not Yet Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: Institute of Hematology & Blood Diseases Hospital, China · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

The aim of this study is to analyze the safety of BAFF-R Chimeric Antigen Receptor T-Cell Injection (BAFF-R CAR-T) in participants with relapsed/refractory BAFF-R-positive B-cell lymphoma and explore the Maximum Tolerated Dose (MTD). The secondary objective of this study is to explore the efficacy of BAFF-R CAR-T in participants with relapsed/refractory BAFF-R-positive B-cell lymphoma. The study also aims to explore the pharmacokinetic characteristics of BAFF-R CAR-T in vivo and the impact of BAFF-R CAR-T on lymphocyte subsets in vivo.

Detailed description

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.

Conditions

• DLBCL
• CLL
• FL
• MCL
• WM
• MZL

Interventions

Type	Name	Description
DRUG	BAFF-R CAR-T	Eligible participants should receive preconditioning 5 to 3 days prior to CAR-T cell infusion. The recommended preconditioning regimen is fludarabine (30 mg/m²/day for 3 days) and cyclophosphamide (300 mg/m²/day for 3 days) (Flu/Cy). Thirty minutes before the infusion, medications for preventing allergic reactions should be administered: 25 mg of promethazine hydrochloride or 12.5 mg of diphenhydramine, which can be given via intramuscular injection or oral administration. In Phase1 bispecific maintenance therapy will be divided into three dose groups, using a "3 + 3" dose escalation design. In Phase 2, the Maximum Tolerated Dose (MTD) identified in Phase 1 will be used, and the study will be expanded to enroll 20 participants.

Timeline

• Start date: 2025-11-29
• Primary completion: 2029-11-28
• Completion: 2029-11-28
• First posted: 2025-12-02
• Last updated: 2025-12-02