BAFF-R CAR-T therapy for relapsed or 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

This trial will test whether a BAFF‑R–targeted CAR‑T cell therapy is safe and can help adults with relapsed or refractory BAFF‑R–positive B‑cell lymphomas (such as DLBCL, CLL, FL, MCL, or WM).

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Institute of Hematology & Blood Diseases Hospital, China (Academic / other)
• Drugs / interventions: CAR-T, Chimeric Antigen Receptor, chemotherapy
• Locations: 1 site (Tianjin, Tianjin Municipality)
• Trial ID: NCT07259070 on ClinicalTrials.gov

What this trial studies

This is an investigator‑initiated, multicenter dose‑escalation Phase I/II study of a fully human BAFF‑R CAR‑T product in patients with relapsed or refractory BAFF‑R–positive B‑cell lymphomas. A 3+3 design will be used to escalate three dose levels (1 × 10^6, 2 × 10^6, and 3 × 10^6 CAR+ T cells/kg) with a 14‑day spacing rule after the first patient in each cohort and rules for dose‑limiting toxicities to guide escalation. After completing dose escalation, investigators may proceed to a dose expansion cohort based on safety and pharmacokinetic (PK) data. The study will also characterize in vivo PK and effects on lymphocyte subsets while monitoring for adverse events and preliminary anti‑tumor activity.

Who should consider this trial

Good fit: Adults with relapsed or refractory BAFF‑R–positive B‑cell lymphoma confirmed per guidelines, with at least one measurable lesion or bone marrow involvement and BAFF‑R expression confirmed by flow cytometry, are the intended candidates.

Not a fit: Patients whose tumors do not express BAFF‑R, who cannot undergo required testing or lymphodepleting procedures, or who have uncontrolled comorbidities or active severe infections are unlikely to benefit from this therapy.

Why it matters

Potential benefit: If successful, BAFF‑R CAR‑T could offer a new targeted therapy that produces remissions in patients whose B‑cell lymphomas have returned or not responded to prior treatments.

How similar studies have performed: CAR‑T therapies targeting CD19 have shown clear success in many B‑cell lymphomas, but BAFF‑R‑directed CAR‑T is a newer strategy with limited clinical data to date.

Eligibility criteria

Inclusion Criteria:

1.Relapsed and refractory (R/R) BAFF-R-positive B-cell lymphoma:The diagnosis of B-cell lymphoma must be confirmed in accordance with the NCCN Clinical Practice Guidelines in Oncology: B-Cell Lymphomas (Version 1.2020) (NCCN: National Comprehensive Cancer Network).The expression of BAFF-R on tumor cells must be detected by flow cytometry (for patients where current clinical sampling is not feasible, test results obtained within 90 days prior to signing the informed consent form are acceptable). Investigators will determine whether to accept test results from external hospitals and whether the patient is eligible for enrollment.In accordance with the 2014 Lugano Classification, B-cell lymphoma patients must have at least one measurable lesion with a longest diameter ≥ 1.5 cm, or bone marrow involvement confirmed by bone marrow flow cytometry.Patients who have received CD19-targeted therapy are also eligible for enrollment, including those who have undergone:

1. :Relapsed and refractory (R/R) mantle cell lymphoma (MCL):Histologically confirmed MCL;Relapsed or refractory after at least 2 lines of prior treatment (including anti-CD20 monoclonal antibody and Bruton's tyrosine kinase inhibitor \[BTKi\]).
2. :Relapsed and refractory (R/R) chronic lymphocytic leukemia (CLL):Histologically confirmed CLL;Patients who have received at least immunochemotherapy and are refractory to both BTK inhibitors and B-cell lymphoma 2 (BCL2) inhibitors.
3. :Relapsed and refractory (R/R) diffuse large B-cell lymphoma (DLBCL):Histologically confirmed DLBCL;Patients who have received anthracycline-based therapy and anti-CD20 monoclonal antibody therapy, and have undergone at least 2 lines of treatment in total; or patients who failed to achieve remission, progressed, or relapsed within 12 months after initial standard treatment.
4. :Relapsed and refractory (R/R) follicular lymphoma (FL):Histologically confirmed FL (Grade 1-3a);Patients who have received anti-CD20 monoclonal antibody-containing therapy and have undergone at least 2 lines of treatment in total; or patients who relapsed within 24 months after initial treatment.
5. :Relapsed and refractory (R/R) marginal zone lymphoma (MZL):Histologically confirmed MZL;Patients who have received anti-CD20 monoclonal antibody-containing therapy, have undergone at least 2 lines of treatment in total and relapsed thereafter; or patients who relapsed within 24 months after initial treatment.
6. :Relapsed and refractory (R/R) Waldenström macroglobulinemia (WM):Histologically confirmed WM;Patients who have received anti-CD20 monoclonal antibody-containing therapy and BTK inhibitor-containing therapy (among other medications), and have undergone at least 2 lines of treatment in total; or patients who relapsed within 24 months after initial treatment.

2.Aged ≥ 18 years and ≤ 75 years, with no restriction on gender. 3.Expected survival time ≥ 12 weeks. 4.Serum total bilirubin ≤ 37.2 μmol/L (for patients with Gilbert syndrome: serum total bilirubin ≤ 3.0 × upper limit of normal \[ULN\], direct bilirubin ≤ 1.5 × ULN); estimated glomerular filtration rate \[eGFR\] (calculated by CKD-EPI formula) ≥ 30 ml/min/1.73m²; alanine aminotransferase \[ALT\] and aspartate aminotransferase \[AST\] \< 2.5 × upper limit of normal \[ULN\].

5.Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. 6.Left ventricular ejection fraction (LVEF) ≥ 50% as diagnosed by echocardiography; oxygen saturation \> 91%.

7.The participant and their spouse/partner must agree to use effective barrier or pharmaceutical contraceptive methods from the time the participant signs the informed consent form until one year after CAR-T cell infusion. For female participants of childbearing potential, serum or urine pregnancy test results must be negative during the screening period.

8.Voluntarily participate in this trial and sign the Informed Consent Form (ICF).

1. ： The patient has a full understanding of this study, voluntarily agrees to participate, and signs the Informed Consent Form (ICF).
2. ：Aged ≥ 18 years and ≤ 75 years, with no restriction on gender.

Exclusion Criteria:

1. Patients with a history of allergy to any component of the cellular product.
2. Patients with acute graft-versus-host disease (aGVHD) graded as Grade II-IV according to the Glucksberg criteria, or with severity graded as Grade B-D according to the IBMTR index; patients with acute or chronic graft-versus-host disease (cGVHD) requiring systemic treatment within 4 weeks prior to enrollment.
3. Participants who have received a live vaccine injection within 4 weeks prior to enrollment.
4. Patients with central nervous system (CNS) diseases unrelated to lymphoma central nervous system involvement (e.g., cerebral aneurysm, epilepsy, stroke, Alzheimer's disease, psychiatric disorders, etc.). Lymphoma central nervous system involvement or gastrointestinal tract involvement is not an exclusion criterion, but eligibility for enrollment shall be determined by the investigator.
5. Patients with severe active infections (except uncomplicated urinary tract infections and bacterial pharyngitis), or those currently receiving intravenous antibiotic therapy. However, prophylactic use of antibiotics, antiviral drugs, and antifungal drugs is permitted.
6. Patients who are positive for hepatitis B surface antigen (HBsAg) or positive for hepatitis B virus (HBV) DNA in peripheral blood.
7. Patients who are positive for hepatitis C virus (HCV) antibody and positive for hepatitis C virus (HCV) RNA in peripheral blood.
8. Patients with other acquired or congenital immunodeficiency diseases, including but not limited to those positive for human immunodeficiency virus (HIV) antibody; patients with cytomegalovirus (CMV) DNA test value \> 400 copies/mL; patients with positive syphilis test results.
9. Patients with heart failure classified as Grade III or IV according to the New York Heart Association (NYHA) Functional Classification (see Appendix II).
10. Patients with a history of other primary malignancies, except for the following cases:Non-melanoma skin cancer (e.g., basal cell carcinoma of the skin) cured by resection;In situ carcinoma cured (e.g., cervical cancer, bladder cancer, breast cancer, etc.);Other primary malignancies with no recurrence detected for more than 5 years after treatment.
11. Patients with a history of solid organ transplantation.
12. Patients with a history of autoimmune diseases (predominantly characterized by abnormal cellular immunity), as well as patients with immunodeficiency or those requiring immunosuppressive therapy.
13. Patients who received investigational drugs from other interventional clinical trials within 3 months prior to signing the Informed Consent Form (ICF).
14. Pregnant women or women who are breastfeeding.
15. Patients with psychiatric disorders, consciousness disturbances, or central nervous system (CNS) diseases.
16. Patients whose toxic effects from prior treatment have not resolved to baseline or ≤ Grade 2 (per NCI-CTCAE Version 5.0, alopecia excluded).
17. Medication use:Corticosteroids: Use of therapeutic-dose corticosteroids within 72 hours prior to CAR-T cell infusion; however, physiological-dose corticosteroid replacement is permitted (hydrocortisone \< 12 mg/m²/day or its equivalent dose)；Systemic antineoplastic therapy: Failure to discontinue systemic antineoplastic therapy for at least 2 weeks or 5 drug half-lives prior to T cell apheresis (except for BTK inhibitors in patients with CLL); the interval between T cell apheresis and the use of immune checkpoint inhibitors is less than 3 drug half-lives.
18. Patients with active pulmonary infections.
19. Patients with contraindications to peripheral blood apheresis.
20. Patients deemed unsuitable for participation in this trial by the investigator after careful consideration for other reasons.

Where this trial is running

Tianjin, Tianjin Municipality

• Institute of Hematology and Blood Diseases Hospital ,Chinese Academy of Medical Sciences — Tianjin, Tianjin Municipality, China (Recruiting)

Study contacts

• Study coordinator: Shuhua Yi,Dr

Conditions DLBCL; CLL; FL; MCL; WM; MZL