To Investigate the Safety and Preliminary Efficacy of EBV CAR-T Cells in the Treatment of Relapsed/Refractory EBV-positive Nasopharyngeal Carcinoma
试验速览
- 阶段
- 早期 1 期
- 状态
- 招募中
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Dose-limiting toxicity（DLT）
研究概览
简要总结
The aim of this study is to investigate the safety and preliminary efficacy of EBV CAR-T cells in the treatment of relapsed/refractory NPC
详细描述
The investigators designed a single-arm, open-label, "3+3" dose-escalation exploratory study. According to the subject and dose escalation test, the maximum dose or the best effective dose was determined to verify the safe and effective number of cells per body weight. A "3+3" dose escalation design was used to set three dose groups of gradually increasing CAR-T cells for therapeutic evaluation. The dose groups were 3.0×10^6cells/kg, 9.0×10^6cells/kg and 1.5×10^7cells/kg, respectively. Cell reinfusion will take place on day 0 (d0) and each subject will be observed for at least 4 weeks after receiving cell reinfusion (DLT observation period).
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
- •Voluntarily sign written informed consent;
- •Age ≥18, ≤75 years old, male and female;
- •3 )Estimated survival ≥ 3 months;
- •ECOG physical fitness score was 0-2;
- •EBV positive nasopharyngeal carcinoma was diagnosed;
- •Positive target detection;
- •At least one measurable lesion according to RECIST V1.1 solid tumor evaluation criteria;
- •Patients with recurrent/metastatic nasopharyngeal carcinoma who had previously failed second-line or higher systemic therapy;
- •Monopheresis or venous blood collection venous access can be established, and there are no other contraindications for blood cell separation;
- •Full organ and bone marrow function,
- •Toxicity and side effects left by previous anti-tumor therapy (radiotherapy, chemotherapy, targeted therapy, etc.) ≤ grade 1 (CTCAE 5.0);
- •Fertile subjects (male or female) must use effective medical contraception during the study period and for 6 months after the end of administration. In female subjects of reproductive age, a negative pregnancy test should be performed within 72 h prior to the first dose.
排除标准
- •There are active CNS metastases (except those stabilized by treatment);
- •HIV positive, HBsAg positive, HBV DNA copy number positive (quantitative test ≥1000cps/ mL), HCV antibody positive and HCV RNA positive;
- •Those with mental or psychological diseases who cannot cooperate with treatment and efficacy evaluation;
- •subjects with severe autoimmune diseases and long-term use of immunosuppressants;
- •Within 14 days prior to enrollment, there were active or uncontrollable infections requiring systemic treatment;
- •Any unstable systemic disease
- •Complicated with lung, brain, kidney and other important organ dysfunction;
- •Subjects have undergone major surgery or trauma in the 4 weeks prior to receiving cell therapy, or are expected to undergo major surgery during the study period;
- •Subjects received their last radiotherapy or anti-tumor therapy (chemotherapy, targeted therapy, or immunotherapy) within 4 weeks prior to receiving cell therapy;
- •The subject currently has or has had other malignancies that cannot be cured within 3 years, except cervical carcinoma in situ or basal cell carcinoma of the skin, and other malignancies with disease-free survival of more than 5 years;
- •T cells modified with chimeric antigen receptor (CAR T, TCR-T) within six months;
- •Combined graft versus host disease (GVHD);
- •Subjects who were receiving systemic steroids prior to screening and determined by the investigator to require long-term systemic steroid use during treatment (other than inhalation or topical use); And subjects who were treated with systemic steroids (except for inhalation or topical use) within 72 h prior to cell infusion;
- •A history of severe allergies or allergies;
- •Subjects requiring anticoagulant therapy;
- •Women who are pregnant or breast-feeding, or have a pregnancy plan within six months (for both men and women);
- •Researchers believe that there are other reasons not to include patients in the treatment.
研究组 & 干预措施
CAR-T Cell Injection
A total of 24 patients with recurrent or refractory NPC received a single intravenous infusion of CAR-T cells at doses of 3.0 × 10^6cells/kg, 9.0 × 10^6cells/kg, and 1.5 × 10^7cells/kg, respectively, and were enrolled according to the conventional "3+3" dose escalation.
干预措施: CAR-T Cell Injection (Biological)
CAR-T Cell Injection
A total of 24 patients with recurrent or refractory NPC received a single intravenous infusion of CAR-T cells at doses of 3.0 × 10^6cells/kg, 9.0 × 10^6cells/kg, and 1.5 × 10^7cells/kg, respectively, and were enrolled according to the conventional "3+3" dose escalation.
干预措施: Fludarabine (Drug)
CAR-T Cell Injection
A total of 24 patients with recurrent or refractory NPC received a single intravenous infusion of CAR-T cells at doses of 3.0 × 10^6cells/kg, 9.0 × 10^6cells/kg, and 1.5 × 10^7cells/kg, respectively, and were enrolled according to the conventional "3+3" dose escalation.
干预措施: cyclophosphamide (Drug)
结局指标
主要结局
Dose-limiting toxicity（DLT）
时间窗: From day 0 to day 28
Adverse events related to cell therapy were observed on 28 days after CAR-T cell injection , as specified in the protocol
次要结局
- Tmax(12 months)
- AUC(Day 0 to Day 28)(From day 0 to day 28)
- ORR(12 months)
- Cmax(12 months)
- PFS(12 months)
- OS OS(12 months)