A Multicenter Clinical Study on the Safety and Efficacy of Nanobody-based Biepitope CAR-T Cells Targeting BCMA in the Treatment of Relapsed/Refractory Multiple Myeloma

Wuhan Union Hospital, China1 个研究点分布在 1 个国家目标入组 60 人开始时间: 2024年4月23日最近更新: 2024年7月16日

适应症

干预措施

试验速览

阶段: 1 期
状态: 招募中
发起方
入组人数: 60
试验地点: 1
主要终点: Overall response rate (ORR) of nanobody-based biepitope CAR-T cells targeting BCMA in R/R MM

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

To explore the safety and efficacy of nanobody-based BCMA-targeting biepitope CAR-T cells in the treatment of relapsed/refractory multiple myeloma，this study will be conducted in multiple study centers, with 60 patients openly enrolled to receive CAR-T cell therapy. Patients participating in clinical trials will be tested and evaluated for treatment safety, efficacy, duration of response, and long-term survival.

详细描述

This study is a multicenter, open-label, prospective, single-arm clinical study with patients with relapsed/refractory multiple myeloma as the test subjects, in order to evaluate the safety and efficacy of nanobody-based biepitope CAR-T cells targeting BCMA in the treatment of R/RMM, and to collect CAR-T PK/PD indicators. The structure of BCMA target CAR-T is designed to identify two different epitopes of BCMA protein with two recognition domains, in order to killig MM cells without secreting more pro-inflammatory factors and avoiding escape caused by the limitations of single BCMA antigen recognition.

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

•Patient or his or her legal guardian voluntarily participates in and signs an informed consent form.
•Aged ≥ 18 years and ≤ 75 years.
•Diagnosed as Multiple Myeloma (MM) according to the international standard for multiple myeloma (IMWG 2014).
•Diagnosed as relapsed/refractory disease or primary refractory disease; relapse is defined as disease progression within 60 days of the most recent treatment with three or more lines of therapy with different mechanisms of action; refractory is defined as failure to achieve MR or above efficacy with prior treatment and disease progression with recent treatment, or disease progression within 60 days of treatment.
•Flow cytometry or immunohistochemistry showed positive BCMA expression in myeloma cells.
•Have not been treated with antibody-based drugs within 2 weeks prior to cell therapy.
•ECOG score 0-2 points.
•HGB≥70g/L，PLT≥30×10^9/L.
•Liver, kidney and cardiopulmonary functions meet the following requirements:
•Serum creatinine ≤ 1.5× ULN or creatinine clearance (Cockcroft-Gault) >30 ml/min；
•Left ventricular ejection fraction (LVEF) ≥50%,
•Baseline peripheral oxygen saturation > 90%;
•Total bilirubin ≤ 1.5×ULN; ALT and AST ≤2.5×ULN.

排除标准

•Previous diagnosis and treatment of other malignancies within 3 years;
•Presence of one of the following cardiac criteria: atrial fibrillation; Myocardial infarction within the last 12 months; Prolonged QT syndrome or secondary QT prolongation, as judged by the investigator. Echocardiogram LVSF <30% or LVEF <50%; Clinically significant pericardial effusion; Cardiac insufficiency NYHA (New York Heart Association) III or IV (absence of this symptom confirmed by echocardiography within 12 months of treatment);
•Patients with active GVHD;
•Patients with a history of severe pulmonary impairment disease;
•Combined with other malignant tumors in the advanced stage;
•Co-infection with severe or persistent infection that cannot be effectively controlled;
•Combined with severe autoimmune disease or congenital immunodeficiency;
•Active hepatitis (hepatitis B virus deoxyribonucleic acid [HBV-DNA ≥ 500 IU/ml and abnormal liver function] or hepatitis C antibody [HCV-Ab] positive, HCV-RNA above the lower limit of detection of the analytical method and abnormal liver function);
•Human immunodeficiency virus (HIV) infection or syphilis infection;
•Patients with a history of severe allergy to biological products (including antibiotics);
•Patients with central nervous system disorders such as uncontrolled epilepsy, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, etc;
•Pregnant or Lactating Women; Patients and his or her spouses have a fertility plan within 12 months after CAR-T cell infusion;
•Other conditions considered inappropriate by the researcher.

研究组 & 干预措施

Effective of nanobody-based biepitope BCMA-targeting CAR-T cells

Experimental

The recommended reinfusion dose of biepitope BCMA-targeting CAR-T cells in this trial is: 1 × 10^6/kg, 2 × 10^6/kg CAR-T cells.

干预措施: Nanobody-based biepitope BCMA-targeting CAR-T cells (Drug)