NCT05741359招募中1 期
A Phase I/II Clinical Study of the Safety and Efficacy of CD19-targeted Non-viral PD1 Site-specific Integrated CAR-T Cell Injection (BRL-201) in the Treatment of Relapsed or Refractory B Lymphocyte Non-Hodgkin Lymphoma
Bioray Laboratories3 个研究点 分布在 1 个国家目标入组 18 人开始时间: 2023年4月25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
- 发起方
- 入组人数
- 18
- 试验地点
- 3
- 主要终点
- DLT
研究概览
简要总结
This is a multi-center, single-arm, open-label clinical study, and the sample size is set to 12-18 subjects.
详细描述
This is a multi-center, single-arm, open-label clinical study, and the sample size is set to 12-18 subjects. Based on the "3 + 3" dose escalation design principle, subjects will be divided into 3 groups from low dose to high dose in sequence (Group A; Group B; Group C. Additional subjects will be enrolled into the RP2D group to ensure that 6-9 efficacy-evaluable subjects are available in the RP2D group before entering the phase II study.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Willing to participate in this clinical study and sign an informed consent form;
- •Age ≥ 18 years old;
- •Estimated survival time ≥ 3 months;
- •Presence of at least one measurable lesion as assessed according to Lugano Classification 2014 for response assessment in lymphomas (i.e., the cross-sectional images obtained by CT show that the long diameter of lymph node lesions is > 15 mm or the long diameter of extranodal lesions is > 10 mm, and FDG-PET scan results are positive). Lesions, for which radiotherapy was provided, can be regarded as measurable lesions only if there is an unequivocal progression after radiotherapy;
- •Histopathologically confirmed aggressive B-NHL; positive expression of CD19 in tumors detected by immunohistochemistry or flow cytometry; pathological types of B-NHL (according to WHO Lymphoma Classification 2016);
- •Relapsed or refractory diseases;
- •Subjects who must receive adequate prior therapy;
- •Absence of invasion of central nervous system (CNS) lymphoma by cranial magnetic resonance imaging (MRI);
- •Hematological parameters meeting the requirements;
- •Blood biochemistry meeting the requirements;
- •LVEF ≥ 55%;
- •No severe pulmonary disorders;
- •Toxic reactions induced by prior anti-lymphoma therapy must be stable and resolved to grade ≤ 1;
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1;
- •Patients with physical conditions for apheresis of peripheral blood; 16 . Willing to abide by the rules formulated in the study protocol.
排除标准
- •Pregnant or lactating women;
- •Subjects who previously received allogeneic cell therapies, including allogeneic stem cell transplant;
- •Subjects who previously received anti-CD19 targeted therapy, except those who receive BRL-201 and are eligible to receive reinfusion in this study;
- •Prior treatment with any CAR-T cell product or other genetically modified T cell therapies;
- •History of Richter's transformation of chronic lymphocytic leukemia (CLL);
- •Presence of uncontrollable fungal, bacterial, viral, or other infections requiring systemic therapy. Patients can be enrolled if the simple urinary tract infection or pharyngitis responds to treatment;
- •Subjects with positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) and peripheral blood HBV DNA titer higher than the upper limit of detection; hepatitis C virus (HCV) antibody positive and peripheral blood HCV RNA positive; human immunodeficiency virus (HIV) antibody positive; syphilis test positive;
- •Severe mental disorders; history of CNS disorders (e.g., epileptic seizure, cerebrovascular ischemia/hemorrhage, dementia, cerebellar diseases, or any CNS-involved autoimmune disorders);
- •Active autoimmune disorders requiring immunotherapy, including but not limited to end organ damages caused by autoimmune disorders (e.g., Crohn's disease, rheumatoid arthritis, and systemic lupus erythematosus) in the past 2 years, or requiring systemic application of immunosuppressive drugs or other drugs for systemic control of diseases;
- •Primary immunodeficiency;
- •History of other malignancies;
- •Patients with severe cardiovascular disorders, including but not limited to those with lymphoma infiltration in the cardiac atrium or ventricles and those with a history of myocardial infarction, cardioangioplasty or stent implantation, unstable angina, or other clinically significant heart diseases within 12 months before enrollment;
- •History of deep venous thrombosis or pulmonary embolism within 6 months before enrollment;
- •Patients who are receiving oral anticoagulant therapy; prothrombin time (PT), activated partial thromboplastin time (APTT), or international normalized ratio (INR) > 1.5 × ULN without anticoagulant therapy;
- •Presence of any indwelling tube or catheter (e.g., tube or catheter for percutaneous nephrostomy, indwelling catheter, or catheter in pleural cavity/peritoneal cavity/pericardium). Dedicated central venous access catheters (e.g., Port-a-Cath or Hickman catheter) are permitted;
- •Lymphoma cells detected in cerebrospinal fluid, presence of brain metastases, history of CNS lymphoma, or history of lymphoma cells detected in cerebrospinal fluid or brain metastases;
- •Conditions (e.g., intestinal obstruction or vascular compression) requiring emergency treatment due to tumor masses;
- •History of severe immediate hypersensitivity to any drug to be used in this study;
- •Vaccination of live vaccines, excluding corona virus disease 2019 (COVID-19) vaccines, within ≤ 6 weeks before the start of the pretreatment regimen;
- •Any circumstances that possibly increase the risk of subjects or interfere with the study results as judged by the investigator.
研究组 & 干预措施
Treatment group
Experimental
5- 10.0×10^6/kgBW
干预措施: CD19-targeted non-viral PD1 site-specific integrated CAR-T cell injection (Drug)
结局指标
主要结局
DLT
时间窗: Within 28 Days After BRL-201 Infusion
The number and severity of dose-limiting toxicity (DLT) events
AEs
时间窗: Up to 24 Months After BRL-201 Infusion
The total number, incidence, and severity of AEs
RP2D
时间窗: Within 28 Days After BRL-201 Infusion
The recommended phase 2 dose
次要结局
未报告次要终点
研究者
研究点 (3)
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