Phase 1, Open-label, Single-arm, Dose-escalation Clinical Study Evaluating the Safety and Efficacy of ET190L1-ARTEMIS™2 in Relapsed, Refractory B Cell Leukemia and Lymphoma
试验速览
- 阶段
- 早期 1 期
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose
研究概览
简要总结
Clinical study to evaluate safety and pharmacokinetics (primary objectives) and efficacy (secondary objective) of ET190L1-ARTEMIS™2 T-cells in patients with Cluster of Differentiation (CD) 19+ B cell Leukemia and Lymphoma
详细描述
ARTEMIS™ is a novel chimeric T-cell therapy that in pre-clinical studies, functionally matches the efficacy of Chimeric Antigen Receptor (CAR) T cells, but dramatically reduces the release of cytokines upon killing of target positive tumors. The molecular target for ET190L1-ARTEMIS™ is Cluster of Differentiation 19 (CD19), which is expressed on B cell Lymphomas and B cell Leukemias. ET190L1-ARTEMIS™ is a second generation ARTEMIS™ receptor engineered with a human Fab antibody domain against CD19. This clinical study evaluates the safety and pharmacokinetics of ET190L1-ARTEMIS™ T-cells in patients with relapsed/refractory B-cell lymphoma and B-cell Leukemia.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Patients with relapsed/refractory CD19+ B-cell lymphoma or Leukemia, with no effective therapy available per National Comprehensive Cancer Network (NCCN) guidelines
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤2, expected survival time > 3 months per PIs opinion
- •Women of childbearing age should have a negative pregnancy test and agree to use effective contraception during treatment and 1 year after the last dose.
- •Peripheral venous access is available and no issues with apheresis for lymphocyte isolation
- •serum alanine aminotransferase(ALT)<200 Unit/L, ALT/Aspartate aminotransferase(AST)<3 normal range; serum creatinine (Cr)<2.5mg/dL
- •Voluntarily signed informed consent form
排除标准
- •Women in pregnancy and lactation
- •Unable to perform leukapheresis and iv infusion
- •With active infection
- •Major organ failure
- •Patients with dependence on corticosteroids
- •Continuously used glucocorticoids or other immunosuppressive agents within 2 weeks
- •T cell deficiency or T cells are difficult to be transduced
- •Patients currently receiving other investigational treatments (biotherapy, chemotherapy, or radiotherapy)
结局指标
主要结局
Maximum Tolerated Dose
时间窗: 28 days up to 2 years
Determine the safety, including potential dose limiting toxicities, of the ET190L1-ARTEMIS™ T cells. A dose limiting toxicity is defined as any toxicity that is considered to be primarily related to the ET190L1-ARTEMIS™ T cells, which is irreversible or life threatening or CTCAE Grade 3-5. Assessed at all visits.
Number of ET190L1-ARTEMIS™ T cells in peripheral blood
时间窗: 24 months
Duration of in vivo engraftment of ET190L1-ARTEMIS™ T cells. Number of ET190L1-ARTEMIS™ T cells in peripheral blood will be presented as Time to peak, Time to baseline level and so on.
% of ET190L1-ARTEMIS™ T cells in peripheral blood
时间窗: 24 months
Duration of in vivo engraftment of ET190L1-ARTEMIS™ T cells. % of ET190L1-ARTEMIS™ T cells in peripheral blood will be presented as Time to peak, Time to baseline level and so on.
Frequency of ARTEMIS T cell treatment-related adverse events
时间窗: until 24 weeks
Frequency of treatment-related adverse events that occurred at any time from the first day of infusion that are "possibly", "likely", or "definitely" related to the study, including infusion related toxicity and ET190L1-ARTEMIS™ T T cells related toxicity. Include but not limited to: Fever, chills, nausea, vomiting, jaundice and other gastrointestinal symptoms; Fatigue, hypotension, respiratory distress; Tumor lysis syndrome; Cytokine release syndrome; Neutropenia, thrombocytopenia; Liver and kidney dysfunction. Assessed at all visits.
次要结局
- Median Survival（MS）(4 months, 1 year and 2 years)
- Overall Survival（OS）(4 months, 1 year and 2 years)
- AUC of serum cytokine levels(24 weeks)
- Rate of disease response(28 days to 24 months)
- Progression free survival (PFS)(4 months, 1 year and 2 years)
- Tmax of serum cytokine levels(24 weeks)
- B cell depletion (%)(2 years)
- B cell depletion (Number)(2 years)
- Time to baseline for serum cytokine levels(24 weeks)