BAFFR CAR-T therapy for relapsed or treatment-resistant B‑cell cancers

A Clinical Study Evaluating the Safety and Efficacy of BAFFR CAR-T Therapy for Relapsed/Refractory B-cell Malignancies

This study will try BAFFR-directed CAR-T cell therapy in adults whose B‑cell cancers have come back or not responded to prior treatments to see if it is safe and works.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 28 (estimated)
• Ages: 18 Years to 78 Years
• Sex: All
• Sponsor: Tongji Hospital (Academic / other)
• Drugs / interventions: CAR-T
• Locations: 1 site (Wuhan)
• Trial ID: NCT07345728 on ClinicalTrials.gov

What this trial studies

This is a prospective, single-arm, multi-center interventional study planning to enroll 30 adults with relapsed or refractory B‑cell malignancies to receive an infusion of BAFFR-directed CAR-T cells. Eligible patients must have tumor tissue that tests positive for BAFFR, prior exposure to anti‑CD20 and anthracycline-containing regimens, ECOG performance status 0–2, and adequate organ function. Participants will undergo manufacturing and infusion of the CAR-T product with scheduled clinical and laboratory follow-up to monitor safety, treatment-related toxicities, and anti-tumor activity. The study is led by Tongji Hospital (Wuhan) and includes centralized administration and post-infusion monitoring for response and adverse events.

Who should consider this trial

Good fit: Ideal candidates are adults age 18–85 with relapsed or refractory B‑cell lymphoma who are BAFFR-positive, have received prior anti‑CD20 and anthracycline therapies, have ECOG 0–2, and meet the study's organ function requirements.

Not a fit: Patients with BAFFR‑negative tumors, significant organ dysfunction, uncontrolled infections, or poor performance status beyond ECOG 2 (or other conditions preventing CAR‑T infusion) are unlikely to benefit from this therapy.

Why it matters

Potential benefit: If successful, BAFFR CAR-T could provide a new targeted option that produces remissions for patients whose B‑cell malignancies have relapsed or failed prior therapies.

How similar studies have performed: CAR‑T therapies targeting other B‑cell antigens such as CD19 have achieved durable remissions in relapsed/refractory disease, but BAFFR-directed CAR‑T is a newer approach with limited published human data.

Eligibility criteria

Inclusion Criteria:

Patients or their guardians understand and voluntarily sign the informed consent form, and are expected to complete the follow-up examinations and treatment procedures of the study; Age 18-85 years (inclusive), gender not restricted; Patients with relapsed/refractory B-cell lymphoma who have received prior treatment including anti-CD20 targeted agents (unless documented CD20 negative) and anthracycline-containing regimens; Pathological immunohistochemistry of tumor confirms positive BAFFR target expression at screening; Patients have recovered from the toxicities of previous treatments, i.e., CTCAE toxicity grade \< 2 (unless abnormalities are tumor-related or judged by the investigator to be stable and not significantly affecting safety or efficacy); ECOG performance status 0-2 and life expectancy \> 3 months;

Adequate organ function:

1. Alanine transaminase (ALT) ≤ 3 × upper limit of normal (ULN);
2. Aspartate transaminase (AST) ≤ 3 × ULN;
3. Total bilirubin ≤ 1.5 × ULN;
4. Serum creatinine ≤ 1.5 × ULN, or creatinine clearance ≥ 60 mL/min;
5. Hemoglobin ≥ 60 g/L or maintained at this level after transfusion;
6. Room air oxygen saturation ≥ 92%;
7. Left ventricular ejection fraction (LVEF) ≥ 45%; Accessible venous access for apheresis and no contraindications to leukapheresis.

Exclusion Criteria:History of other malignancies within 3 years prior to screening, except for adequately treated carcinoma in situ of the cervix, papillary thyroid cancer, basal or squamous cell skin cancer, localized prostate cancer after radical therapy, and ductal carcinoma in situ after radical therapy; Positive for hepatitis B surface antigen (HBsAg), or positive for hepatitis B core antibody (HBcAb) with peripheral blood HBV DNA titer above the lower limit of detection of the research institution; positive for hepatitis C virus (HCV) antibody with positive peripheral blood HCV-RNA; positive for human immunodeficiency virus (HIV) antibody; History of severe allergies \[severe allergy is defined as grade 2 or higher allergic reaction with any of the following clinical manifestations: airway obstruction (runny nose, cough, wheezing, dyspnea), tachycardia, hypotension, arrhythmia, gastrointestinal symptoms (nausea, vomiting), incontinence, laryngeal edema, bronchospasm, cyanosis, shock, respiratory or cardiac arrest\] or known hypersensitivity to any active ingredients, excipients, murine products, or xenogeneic proteins contained in this study (including lymphodepletion regimen); History of severe cardiac disease, including but not limited to severe arrhythmia, unstable angina, massive myocardial infarction, New York Heart Association class III or IV cardiac insufficiency, myocardial infarction or coronary artery bypass grafting (CABG) within ≤ 6 months prior to screening, history of unexplained syncope not due to vasovagal reaction or dehydration, history of severe non-ischemic cardiomyopathy, refractory hypertension (refractory hypertension is defined as: despite lifestyle modifications, blood pressure remains uncontrolled after \> 1 month of treatment with reasonable, tolerable, and adequate doses of ≥ 3 antihypertensive drugs (including diuretics), or requires ≥ 4 antihypertensive drugs to achieve effective blood pressure control); Unstable systemic disease as judged by the investigator: including but not limited to severe liver, kidney, or metabolic diseases requiring medical treatment; Previous organ transplantation or planned organ transplantation (except hematopoietic stem cell transplantation); Active autoimmune or inflammatory neurological diseases (e.g., Guillain-Barré syndrome (GBS), amyotrophic lateral sclerosis (ALS)) and clinically significant active cerebrovascular disease (e.g., cerebral edema, posterior reversible encephalopathy syndrome (PRES)); Presence of tumor emergencies (e.g., spinal cord compression, bowel obstruction, leukostasis, tumor lysis syndrome, etc.) requiring urgent treatment at screening or before infusion; Uncontrolled bacterial, fungal, viral, or other infections requiring antibiotic treatment; Use of short-acting hematopoietic growth factors affecting blood counts within 1 week, or long-acting hematopoietic growth factors within 2 weeks prior to planned CAR-T manufacturing apheresis, and judged by the investigator to affect cell manufacturing;

Receiving corticosteroids or immunosuppressive drugs within 2 weeks prior to planned CAR-T manufacturing apheresis, and judged by the investigator to affect cell manufacturing:

1. Corticosteroids: Subjects receiving systemic steroid therapy within 2 weeks prior to planned CAR-T manufacturing apheresis and judged by the investigator to require long-term systemic steroid therapy during treatment (except inhaled or topical use); and subjects receiving systemic steroid therapy within 72 hours before cell infusion (except inhaled or topical use);
2. Immunosuppressants: Subjects receiving immunosuppressive agents within 2 weeks prior to planned CAR-T manufacturing apheresis; Major surgery (except diagnostic procedures and biopsies) within 4 weeks prior to lymphodepletion or planned major surgery during the study, or incompletely healed surgical wounds before enrollment; Vaccination with (live-attenuated) viral vaccines within 4 weeks prior to screening; History of severe mental illness; History of alcoholism or substance abuse; Pregnant or lactating women, and female subjects planning pregnancy within 2 years after cell infusion or male subjects whose partners plan pregnancy within 2 years after their cell infusion; Subjects with contraindications to any study procedures or other medical conditions that may pose unacceptable risks according to the investigator's judgment and/or clinical standards.

Where this trial is running

Wuhan

• Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology — Wuhan, China (Recruiting)

Conditions Relapsed/Refractory B-cell Malignancies; relapsed/refractory B-cell malignancies