A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Antitumor Activity of SNC-109 CAR-T Cell Therapy in Subjects With Recurrent Glioblastoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Incidence of treatment related adverse everts
研究概览
简要总结
This is a single arm clinical study to estimate the safety, tolerability and pharmacokinetic (PK) characteristics of Chimeric Antigen Receptor-modified T cells (CAR-T) SNC-109 in patients with recurrent glioblastoma (r-GBM) and preliminarily evaluate the effectiveness, the immunogenicity of the product, as well as their correlation between the changes of cytokines from baseline level after cellular infusion.
详细描述
It is planned to recruit about 16 patients with rGBM subjects. The protocol consists of screening period, Lymphocytes apheresis period, Operation period, pre-infusion evaluation (-2~-1 days), infusion (day 0), infusion observation (day 1-post infusion), and follow-up period (last infusion-720 days). The incidence of dose limitation toxicity (DLT) will be observed within 28 days after the first infusion. Subjects in this study will receive multiple infusions, starting with 2×104 CAR+ T cells/dose in the first subject, and the Safety Review Committee (SRC) will evaluate the subsequent dosing regimen, dose, infusion interval, and number of treatment cycles. Subsequent subjects will be evaluated by the SRC on the basis of available PK and safety data, and the SRC will determine the dosing regimen, dose, infusion interval and number of treatment cycles based on observed evidences.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 and ≤70，both sexes;
- •Diagnosed with a history of glioblastoma, and the recurrent glioblastoma has confirmed by histological/molecular pathology (including astrocytoma World Health Organization (WHO) Grade 4);
- •Karnofsky (KPS) ≥60;
- •The estimated survival time is ≥8 weeks;
- •Blood pregnancy tests for women of childbearing age are negative;
- •The patient himself/herself, and/or his/her legal guardian, agree to participate in the trial and sign the informed consent form.
排除标准
- •Known allergies to study drugs or drugs that may be used in the study;
- •Severe concurrent diseases in the heart, lungs, liver, or other vital organs;
- •Hypertension is poorly controlled or accompanied by hypertensive crisis or hypertensive encephalopathy;
- •In addition to the glioblastoma, with other severe central nervous system diseases or complications or aggressive malignancies;
- •Long-term use of immunosuppressant drugs, or large doses of steroids;
- •Received live or attenuated vaccine or other surgery had no related to GBM within 4 weeks prior to Lymphocytes apheresis;
- •Lymphocytes apheresis or cell infusion combined with infection or unexplained fever.
研究组 & 干预措施
SNC-109 CAR-T Cells
After the operation and pre-infusion evaluation, SNC-109 CAR-T Cells will be evaluated.
干预措施: SNC-109 CAR-T Cells (Drug)
结局指标
主要结局
Incidence of treatment related adverse everts
时间窗: Up to 28 days after first infusion
Incidence of adverse events associated with CAR-T cell transfusion within 28 days of the first infusion, abnormal and clinical significant laboratory results
Tmax of SNC-109 CAR vector copy number
时间窗: within 2 years after first infusion
SNC-109 CAR vector copy number (VCN) time to Cmax(Tmax) in peripheral blood (PB) and cerebrospinal fluid (CSF)
Cmax of SNC-109 Cell count
时间窗: within 2 years after first infusion
SNC-109 cell count maximum (Cmax) in peripheral blood (PB) and cerebrospinal fluid (CSF)
AUC of SNC-109 CAR vector copy number
时间窗: within 2 years after first infusion
SNC-109 CAR vector copy number (VCN) area under the curve (AUC) in peripheral blood (PB) and cerebrospinal fluid (CSF)
Tmax of SNC-109 Cell count
时间窗: within 2 years after first infusion
SNC-109 cell count time to Cmax(Tmax) in peripheral blood (PB) and cerebrospinal fluid (CSF)
AUC of SNC-109 Cell count
时间窗: within 2 years after first infusion
SNC-109 cell count area under the curve (AUC) in peripheral blood (PB) and cerebrospinal fluid (CSF)
Other relevant PK parameters
时间窗: within 2 years after first infusion
Other relevant PK parameters in peripheral blood (PB) and cerebrospinal fluid (CSF)
Cmax of SNC-109 CAR vector copy number
时间窗: within 2 years after first infusion
SNC-109 CAR vector copy number (VCN) maximum (Cmax) in peripheral blood (PB) and cerebrospinal fluid (CSF)
次要结局
- Efficacy assesment for the treatment according to iRANO(within 2 years after first infusion)
- Changes of Cytokines after infusion(within 2 years after first infusion)
- Objective response rate (ORR) after infusion(within 2 years after first infusion)
- Overall survival (OS) after infusion(within 2 years after first infusion)
- Concentration of Human anti-chimeric antibody (HACA)(within 2 years after first infusion)
- Progression free survival (PFS) after infusion(within 2 years after first infusion)