LMP2 Antigen-specific High-affinity T Cell Receptor (TCR)-Transduced Autologous T-cell Therapy for Recurrent and Metastatic Nasopharyngeal Carcinoma, an Open-label, Single-center, Phase I Clinical Trial
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- To Determine the Maximum Tolerated Dose of TCR T-cell Therapy
研究概览
简要总结
In this study, a single-arm, open-labeled clinical trial will be performed to determine the safety and efficacy of EBV TCR-T cells in the treatment of recurrent/metastatic nasopharyngeal carcinoma with positive EBV infection in the Chinese population.
详细描述
All enrolled subjects will be infused with EBV TCR-T cells. The project which enrolls 27 patients, according to the patient's HLA subtypes will be divided into HLA-A2, HLA-A11, HLA-A24 three groups, 9 patients in each group. Using a dose climbing method, each group will be divided into three dose subgroups. In the first dose subgroup, 5×106/kg TCR-T cells will be returned, and in the second dose subgroup, 1×107/kg TCR-T cells will be returned. The third dose subgroup 5 x 107/kg TCR-T cells will be returned.
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
- •Patients with nasopharyngeal carcinoma diagnosed by pathology and EBV infection (EBERs positive ) ; 2.18-70 years old; 3.MHC-I is HLA-A2, HLA-A11 or HLA-A24 subtype;
- •Progression after second-line platinum-containing chemotherapy regimen, recurrent/metastatic nasopharyngeal carcinoma patients who are inoperable and non-radiable;
- •Based on the Response Evaluation Criteria in Solid Tumors version (RECIST 1.1), there are ≥ 1 measurable target lesions;
- •Expected survival time is more than 12 weeks;
- •ECOG score 0-2 points;
- •Patients with good bone marrow, kidney, liver, and heart, and lung function
- •Can establish the venous access required for the collection, no contraindications for white blood cell collection;
- •Male and female patients of the appropriate age must adopt a reliable method of contraception;
- •Those who understand the trial and have signed an informed consent form.
排除标准
- •Patients with symptomatic brain metastasis;
- •Other malignant tumors other than nasopharyngeal carcinoma within 5 years prior to enrollment, in addition to appropriate treatment of cervical carcinoma in situ, cutaneous basal or squamous cell carcinoma, localized prostate cancer or ductal carcinoma in situ after radical surgery ;
- •Hepatitis B or hepatitis C active period, HIV-infected;
- •Any other uncontrolled active disease that impedes participation in the trial;
- •Patients with severe heart and cerebrovascular diseases such as coronary heart disease, angina pectoris, myocardial infarction, arrhythmia, cerebral thrombosis, and cerebral hemorrhage;
- •2-3 grade hypertension or patients with poorly controlled hypertension;
- •Those with a history of mental illness that are difficult to control;
- •The investigator believes that it is not appropriate to participate in the trial;
- •Those who have been using immunosuppressive agents for a long time after organ transplantation, except for recent or current inhaled corticosteroids;
- •In the opinion of the investigator, the presence of medical history or mental state history or laboratory abnormalities may increase the risk associated with participating in the study or study drug administration, or may interfere with the interpretation of the results;
- •Screening indicates that the target cell transfection rate is less than 30%, or the T cell expansion is insufficient (less than 5 times) under CD3/CD28 stimulation conditions;
- •Unstable pulmonary embolism, deep vein thrombosis, or other major arterial/venous thromboembolic events occurred 30 days or 30 days prior to grouping. If receiving anticoagulant therapy, the subject's therapeutic dose must be stable before grouping;
- •A subject who is pregnant or breastfeeding, or who is planning a pregnancy during or after 2 months of treatment;
- •Subjects who are women of childbearing age who are reluctant to receive high-efficiency contraception (according to institutional standards) during treatment and at least 2 months after the end of treatment. Female subjects of childbearing age are required to provide a negative result of a serum or urine pregnancy test within 48 hours prior to treatment;
- •There are active or uncontrollable infections requiring systemic treatment within 14 or 14 days prior to grouping;
- •Subjects who are unwilling or unable to comply with the research requirements.
研究组 & 干预措施
LMP2 Antigen-specific TCR T cells
All enrolled subjects will be infused with EBV TCR-T cells. The project which enrolls 27 patients, according to the patient's HLA subtypes will be divided into HLA-A2, HLA-A11, HLA-A24 three groups, 9 patients in each group. Using a dose climbing method, each group will be divided into three dose subgroups. In the first dose subgroup, 5×106/kg TCR-T cells will be returned, and in the second dose subgroup, 1×107/kg TCR-T cells will be returned. The third dose subgroup 5 x 107/kg TCR-T cells will be returned.
干预措施: LMP2 Antigen-specific TCR T cells (Drug)
结局指标
主要结局
To Determine the Maximum Tolerated Dose of TCR T-cell Therapy
时间窗: 2 years
Verify the MTD of LMP2 Antigen-specific TCR T-cell Therapy
次要结局
未报告次要终点
研究者
Hai-Qiang Mai,MD,PhD
MD,PhD
Sun Yat-sen University