NCT07259070招募中1 期
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
Institute of Hematology & Blood Diseases Hospital, China1 个研究点 分布在 1 个国家目标入组 20 人开始时间: 2025年11月29日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- 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)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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:
- •: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.
- •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-
- •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).
- •： 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.
排除标准
- •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 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.
- •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).
- •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.
- •Patients with active pulmonary infections.
- •Patients with contraindications to peripheral blood apheresis.
- •Patients deemed unsuitable for participation in this trial by the investigator after careful consideration for other reasons.
研究组 & 干预措施
BAFF-R CAR-T for the Treatment of Relapsed and Refractory BAFF-R-Positive B-Cell Lymphoma
Other
干预措施: BAFF-R CAR-T (Drug)
结局指标
主要结局
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)
时间窗: Day 28 after treatment
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).
次要结局
- Objective response rates (ORR)(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)
- Total B Cells (CD19+ B Cells) Absolute Count(Day 28, Month 2, Month 3, Month 6, Month 12，Month 24 after treatment)
- Pharmacokinetics - AUC0-28days(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)
- Pharmacokinetics - Cmax(Day 28, Month 2, Month 3, Month 6, Month 12 ,Month 24 after treatment)
- Pharmacokinetics - Tmax(Day 28, Month 2, Month 3, Month 6, Month 12 ,Month 24 after treatment)
研究者
研究点 (1)
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