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

NCT07259070 | Not Yet Recruiting Phase 1

• 1 other identifier: IIT2025018
• Study Type: interventional
• Target: 20
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

DLBCL; CLL; FL; MCL; WM; MZL

Outcome Measures

Primary Outcomes (1)

• Evaluation of the Safety of BAFF-R Chimeric Antigen Receptor T-Cell Injection (BAFF-R CAR-T) in Subjects with Relapsed and Refractory BAFF-R-Positive B-Cell Lymphoma, and Exploration of the Maximum Tolerated Dose (MTD)

  The possible adverse reactions recorded in each item were evaluated. The highest dose at which fewer than 2 out of 6 subjects (i.e., \< 2/6) experience Dose-Limiting Toxicity (DLT) (with at least 6 subjects in this dose group having received BAFF-R CAR-T infusion and completed the DLT observation period).

  Day 28 after treatment

Secondary Outcomes (8)

• Objective response rates (ORR)

  Day 28, Month 2, Month 3, Month 6, Month 12 ,Month 24 after treatment

• Overall survival (OS)

  Day 28, Month 2, Month 3, Month 6, Month 12 ,Month 24 after treatment

• Progression-free survival (PFS)

  Day 28, Month 2, Month 3, Month 6, Month 12,Month 24 after treatment

• Complete remission rate (CRR)

  Day 28, Month 2, Month 3, Month 6, Month 12,Month 24 after treatment

• Pharmacokinetics - Cmax

  Day 28, Month 2, Month 3, Month 6, Month 12 ,Month 24 after treatment

Study Arms (1)

BAFF-R CAR-T for the Treatment of Relapsed and Refractory BAFF-R-Positive B-Cell Lymphoma

OTHER

Drug: BAFF-R CAR-T

Interventions

BAFF-R CAR-T DRUG

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.

BAFF-R CAR-T for the Treatment of Relapsed and Refractory BAFF-R-Positive B-Cell Lymphoma

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• :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 \[BTKi\]).
• :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.
• :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.
• :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.
• :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.
• :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.
• 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 \[ULN\].
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. 6.Left ventricular ejection fraction (LVEF) ≥ 50% as diagnosed by echocardiography; oxygen saturation \> 91%.
• 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.
• Voluntarily participate in this trial and sign the Informed Consent Form (ICF).
• ： The patient has a full understanding of this study, voluntarily agrees to participate, and signs the Informed Consent Form (ICF).
• ：Aged ≥ 18 years and ≤ 75 years, with no restriction on gender.

You may not qualify if:

• Patients with a history of allergy to any component of the cellular product.
• 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.
• Participants who have received a live vaccine injection within 4 weeks prior to enrollment.
• 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.
• Patients who are positive for hepatitis B surface antigen (HBsAg) or positive for hepatitis B virus (HBV) DNA in peripheral blood.
• Patients who are positive for hepatitis C virus (HCV) antibody and positive for hepatitis C virus (HCV) RNA in peripheral blood.
• 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.
• Patients with heart failure classified as Grade III or IV according to the New York Heart Association (NYHA) Functional Classification (see Appendix II).
• 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.
• Patients with a history of solid organ transplantation.
• Patients with a history of autoimmune diseases (predominantly characterized by abnormal cellular immunity), as well as patients with immunodeficiency or those requiring immunosuppressive therapy.
• Patients who received investigational drugs from other interventional clinical trials within 3 months prior to signing the Informed Consent Form (ICF).
• Pregnant women or women who are breastfeeding.
• Patients with psychiatric disorders, consciousness disturbances, or central nervous system (CNS) diseases.
• Patients whose toxic effects from prior treatment have not resolved to baseline or ≤ Grade 2 (per NCI-CTCAE Version 5.0, alopecia excluded).

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead
• Hebei Taihe Chunyu Biotechnology Co., Ltd: collaborator

Central Study Contacts

Shuhua Yi,Dr

CONTACT

86-22-23608109; yishuhua@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2025
• First Posted: December 2, 2025
• Study Start: November 29, 2025
• Primary Completion (Estimated): November 28, 2029
• Study Completion (Estimated): November 28, 2029
• Last Updated: December 2, 2025

Record last verified: 2025-11