Safety, Tolerability and Efficacy of Enhanced IL-13Rα2 Targeted Chimeric Antigen Receptor T Cell Immunotherapy Against Recurrent/Refractory Grade 4 Glioma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Safety of IL13Rα2 CAR-T
研究概览
简要总结
This is a dose exploration clinical trial to assess the safety and feasibility of the IL13Ra2-targeted CAR-T in glioma.
详细描述
Interleukin 13 receptor subunit alpha-2 (IL13Ra2A) is a high-affinity membrane receptor of the anti-inflammatory Th2 cytokine IL13, which is overexpressed in glioma and correlated with poor prognosis.
Chimeric antigen receptor (CAR) T cell therapy is a promising treatment approach for many malignancies. IL13Ra2-targeted CAR-T cells are under investigation in several clinical trials in primary CNS malignancies.
The investigators now designed a new structure CAR targeted IL13Ra2, and initiated a single arm, open, dose exploration clinical trial to evaluate the safety, tolerability, clinical efficacy, and pharmacokinetic characteristics of IL13Rα2 CAR-T for patients with glioma. This clinical trial will enroll 12-30 cases of patients with IL13α2-positive recurrent or refractory WHO grade 4 glioma (r/r WHO4 glioma), aiming to find the maximum tolerable dose (MTD), the recommended phase 2 dose (RP2D) and preliminary efficacy of the new structure IL13Ra2 CAR-T.
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
- •Male or female aged 18-75 years (including 18 and 75 years old).
- •Karnofsky scale score (KPS)≥
- •Subjects with WHO grade 4 gliomas who have relapsed or progressed during or after standard treatments such as surgery, radiotherapy, and chemotherapy.
- •Tumor with IL13Rα2 positive expression.
- •Availability in collecting peripheral blood mononuclear cells (PBMCs).
- •Adequate laboratory values and adequate organ function.
- •Patients with childbearing/fathering potential must agree to use highly effective contraception.
排除标准
- •Pregnant or breastfeeding females.
- •Contraindication to bevacizumab.
- •Within 5 days prior to the infusion of CAR-T cells, subjects receiving systemic administration of steroids with dosage more than 10mg/d prednisone or the equivalent doses of other steroids (not including inhaled corticosteroid).
- •Comorbid with other uncontrolled malignancy.
- •Active immunodeficiency virus (HIV) or hepatitis B virus or hepatitis C virus or tuberculosis infection.
- •Autoimmune diseases.
- •Severe or uncontrolled psychiatric diseases or condition that could increase adverse events or interfere the evaluation of outcomes.
- •Subjects who have previously received cell therapy (such as TCR-T, CAR-T, TIL, etc.).
- •Subjects with other conditions that would interfere trial participation at the investigator's discretion.
结局指标
主要结局
Safety of IL13Rα2 CAR-T
时间窗: Day 0 - Day 730
The safety of IL13Rα2 CAR-T will be assessed based on the totality of dose-limiting toxicity (DLT) and adverse event (AE) data collected during this phase.
次要结局
- Progression Free Survival (PFS)(Day 0 - Day 730)
- The levels of cytokines in the CSF and peripheral blood(Day 0 - Day 730)
- Duration of Response (DOR)(Day 0 - Day 730)
- Overall Survival (OS)(Day 0 - Day 730)
- Overall Response Rate (ORR)(Day 0 - Day 730)
- The levels of IL13Rα2 CAR-T cell and IL13Rα2 CAR in the CSF and peripheral blood(Day 0 - Day 730)
- Overall Survival (OS) at 12 months (OS12)(Day 0 - Day 365)
- Overall Survival (OS) at 6 months (OS6)(Day 0 - Day 180)
研究者
Yang Zhang
Clinical Professor
Beijing Tiantan Hospital