Clinical Study of CAIX-targeted CAR-T Cells in the Treatment of Advanced Renal Cell Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Effectiveness evaluation
研究概览
简要总结
This is an experimental study to evaluate the safety and efficacy of CAR T cells targeting CAIX in the treatment of advanced renal cancer.
详细描述
We designed a clinical study and divided the trial into two phases.
Phase 1 (climbing test) : 12 patients were randomly divided into 4 groups (n=3). 12 patients were treated with cyclophosphamide at the dose of 60mg/kg/d 8-7 days before CAR-T cell infusion, and fludalabine at the dose of 25mg/m^2/d 6-2 days before CAR-T cell infusion. 5 mg anti-human CAIX monoclonal antibody (G250) was injected into the hepatic artery of each patient by an interventional catheter on the day before CAR-T cells infusion. On Day 0, CAR T cells were injected into patients in group 1, 2, 3 or 4 at the dose of 1x10^7/ person, 1*10^8/ person, 1*10^9/ person or 1*10^10/ person, respectively. The infusion time is about 15-30min. On day 0-14, IL-2 (75000IU/kg) was injected subcutaneously once a day. From day 15-28, IL-2 (75000IU/kg) was subcutaneously injected into the patients three times a week. The purpose of this study is to assess subjects' MTD (maximum tolerated dose) against CAR T cells.
Phase 2: After determining the appropriate therapeutic dose for patients with renal cell carcinoma, 8 patients received the same pre-treatment of chemotherapy and G250 antibody. Then, the appropriate therapeutic dose of CAR T cells according to the results of phase 1 was infused on Day 0. On day 0-14,IL-2 (75000IU/kg) was given subcutaneously once a day. On day 15-28, IL-2 (75000IU/kg) was given subcutaneously three times a week.
Peripheral blood was collected every 4 weeks to evaluate proliferation and survival of CAR-T cells. After 6 months of close follow-up, subjects will undergo a medical history evaluation, physical examination, and blood tests quarterly for 2 years. After this assessment, subjects will be enrolled in an annual telephone follow-up and questionnaire study for up to five years to evaluate treatment for long-term health problems, such as recurrence of malignant tumors.
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
- •Male or female patients aged from 18 to 70 years old;
- •The patient's ECOG score is ≤ 2;
- •Patients with advanced or metastatic renal cell carcinoma:
- •(1) have received first-line and second-line targeted therapy in the past; (2) Previous immunization with PD-1/L1 and ≤2 regimens; (3) Unable to tolerate targeted therapy or immunotherapy. 4.There are measurable or evaluable lesions; 5.The main tissues and organs of patients function well:
- •liver function: ALT/AST< 3 times the upper limit of normal value (ULN);
- •Renal function: creatinine < 220 μmol/L;
- •Lung function: indoor oxygen saturation ≥ 95%;
- •Cardiac function: Left ventricular ejection fraction (LVEF)≥40% 6.Patients or their legal guardians voluntarily participate and sign informed consent.
排除标准
- •Infectious diseases (such as HIV, active hepatitis B or C infection, active tuberculosis, etc.);
- •Feasibility assessment and screening showed that the transfection of targeted lymphocytes was less than 10% or the amplification was insufficient (< 5 times) under the co-stimulation of CD3/CD
- •The vital signs are abnormal, and those who cannot cooperate with the examination;
- •Those who have mental or psychological diseases can not cooperate with treatment and efficacy evaluation;
- •Highly allergic constitution or severe allergic history, especially those who are allergic to IL-2;
- •Subjects with systemic infection or severe local infection who need anti-infection treatment;
- •Complicated with dysfunction of heart, lung, brain, liver, kidney and other important organs;
- •Patients with other tumors;
- •Doctors believe that there are other reasons that can not be included in the treatment.
结局指标
主要结局
Effectiveness evaluation
时间窗: 3 months after CAR-T cells infusion
In order to observe the efficacy of CAR-T cells after infusion, total remission rate (ORR), complete remission (CR), partial remission (PR), disease stability (SD) or progression (PD) will be used for evaluation.
Safety evaluation:Incidence and severity of adverse events
时间窗: First 1 month after CAR-T cells infusion
To evaluate the incidence and severity of possible adverse events within one month after targeted CAIX CAR-T infusion, including cytokine release syndrome and on-target toxicity.
次要结局
- Overall survival (OS)(24 months after CAR-T cells infusion)
- Progression-free survival (PFS)(24 months after CAR-T cells infusion)