A Phase I Clinical Trial of NKG2D-based CAR T-cells Injection for Subjects With Relapsed/Refractory NKG2DL+ Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- 试验地点
- 1
- 主要终点
- Number of Participants with severe cytokine release syndrome(CRS) as a Measure of Safety and Tolerability.
研究概览
简要总结
The primary objective of this study is to evaluate the safety and clinical activity of NKG2D-based CAR-T cells infusion in the treatment of relapsed/refractory NKG2DL+ solid tumors.
详细描述
The preclinical study clarified that NKG2D-based CAR-T cells showed strong cytotoxicity against NKG2DL+ cell lines in vitro as well as a therapeutic effect against NKG2DL+ cell xenografts in vivo. In addition, the data also demonstrated the safety of NKG2D-based CAR-T therapy. NKG2D-based CAR-T represent a potentially effective and safety therapeutic approach for patient with relapsed/refractory NKG2DL+ solid tumors. In this trial, the investigators researched the safety of administering NKG2D-based CAR-T which generated with CD8 hinge region and transmembrane region, 4-1BB costimulatory region and CD3 zeta region. The investigators also assessed that disease response was determined within the context of a phase I trial.
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
- 是
入选标准
- •Men or women≥18 years old,
- •Patient with NKG2DL+ cell tumors confirmed by pathology and histology，
- •Fail or unwilling to receive first-line treatment,
- •Disease must be measurable according to the corresponding guidelines,
- •Main organs function normally and meet following requirements:
- •Routine blood index（No Blood transfusion within 14 days） 1)HB≥90g/L; 2)ANC≥1.5×109/L; 3)PLT≥75×109/L； Serum biochemicals index 1) BIL <1.5 upper normal limit (ULN); 2) ALT and AST<2.5×ULN; In the case of liver metastasis, ALT and AST<5×ULN; 3) Serum Cr≤1×ULN, endogenous creatinine clearance≥50ml/min (Cockcroft-Gault formula); 4) ECOG physical condition score: 0-2
- •Expected survival time ≥3 months,
- •Patient with adequate bone marrow reserve, hepatic and renal functions,
- •No other uncontrolled diseases such as lung, kidney and liver infection before enrollment,
- •Women of child-bearing age must undergo a negative pregnancy test (serum or urine) within 7 days prior to enrollment and voluntarily use appropriate methods of contraception during the observation period and within 8 weeks after the last dose; men should agree to contraception during the observation period and within 8 weeks of the last dose,
- •Patients voluntarily participated in this trial and sign the informed consent form,
- •Patients with compliance and expected to follow up the efficacy and adverse reactions as required by the protocol.
排除标准
- •Pregnant or lactating women,
- •Patients who need to use systemic steroids at the same time,
- •Under following treatment conditions currently: 1) during the other anti- tumor clinical observation period within 14 days before blood collection; 2) patient has not recovered from acute side effects of the previous treatment;
- •Receive radiotherapy within 4 weeks before enrollment,
- •Patients who received any other cell therapy before,
- •Patients with unqualified T cell amplification efficiency,
- •Uncontrolled symptoms or other illnesses, including but not limited to infection, congestive heart failure, unstable angina, arrhythmia, psychosis,
- •Patients with severe acute allergic reactions,
- •Patients who have received other cell therapies,
- •Other serious conditions that may limit patient's participation in the study.
- •Detailed disease specific criteria exist and can be discussed with contacts listed below.
结局指标
主要结局
Number of Participants with severe cytokine release syndrome(CRS) as a Measure of Safety and Tolerability.
时间窗: 0 to 28 days post infusion
The severe CRS post KD-025 CAR-T cells treatment will be evaluated and the maximum tolerated dose will be determined.
Copies numbers of CAR
时间窗: 1 year post infusion
Copies numbers of CAR in peripheral blood (PB)
次要结局
- Duration of response, (DoR)(2 years post infusion)
- overall survival (OS)(2 years post infusion)
- Progress Free Survival (PFS)(2 years post infusion)