Phase Ib, Open-Label Study of CART-EGFR-IL13Rα2 Cells Administered Following Lymphodepleting Chemotherapy or Prior to Surgical Resection in Patients With EGFR-Amplified Recurrent Glioblastoma
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 12
- 试验地点
- 3
- 主要终点
- Number of Subjects with treatment related adverse events using NCI Common Terminology Criteria for Adverse Events (CTCAE) V5.0
研究概览
简要总结
This is an open-label, phase 1b study to evaluate different approaches for CART-EGFR-IL13Ra2 dosing and further characterize the safety, feasibility, preliminary efficacy, and pharmacokinetics of CART-EGFR-IL13Ra2 cells in patients with EGFR-amplified glioblastoma that has recurred following prior radiotherapy.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed, written informed consent
- •Male or female age ≥ 18 years
- •Patients with glioblastoma, IDH-wildtype (as defined by WHO 2021 Classification of CNS Tumors) that has recurred following prior radiotherapy
- •For patients with tumors harboring methylation of the MGMT promoter, a t l east 1 2 w eeks must have elapsed since completion of first-line radiotherapy.
- •Tumor tissue positive for wild-type EGFR amplification by NeoGenomics Laboratories. Archival tumor from patient's initial surgery at time of original diagnosis or recently collected tumor from time of recurrence are acceptable.
- •Surgical tumor resection for disease control/management (Arms A, B, C) or tumor biopsy to confirm tumor recurrence (Arms A and B only) is clinically indicated in the opinion of the physician-investigator.
- •Adequate organ function defined as:
- •Serum creatinine ≤ 1.5 x ULN or estimated creatinine clearance ≥ 30 ml/min and not on dialysis.
- •ALT/AST ≤ 3 x ULN
- •Total bilirubin ≤ 2.0 mg/dL, except for patients in whom hyperbilirubinemia is attributed to Gilbert's syndrome (≤ 3.0 mg/dL)
- •Left Ventricular Ejection Fraction (LVEF) ≥ 45% confirmed by ECHO/MUGA
- •Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygen > 92% on room air
- •Karnofsky Performance Status ≥ 60%.
- •Subjects of reproductive potential must agree to use acceptable birth control methods, as described in protocol Section 4.3.
排除标准
- •Active hepatitis B or hepatitis C infection.
- •Any other active, uncontrolled infection.
- •Class III/IV cardiovascular disability according to the New York Heart Association Classification
- •Tumors primarily localized to the brain stem or spinal cord.
- •Severe, active co-morbidity in the opinion of the physician-investigator that would preclude participation in this study.
- •Receipt of bevacizumab within 3 months prior to physician-investigator confirmation of eligibility.
- •Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to ≥ 10 mg daily of prednisone. Patients with autoimmune neurological diseases (such as MS or Parkinson's) will be excluded.
- •Patients who are pregnant or nursing (lactating).
- •History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).
研究组 & 干预措施
Arm B
Subjects will receive repeated dose administration of CART-EGFR-IL13Ra2 cells following lymphodepletion.
干预措施: CART-EGFR-IL13Ra2 T cells (Biological)
Arm C
Subjects will receive a single fixed-dose administration of CART-EGFR-IL13Ra2 in the pre-operative setting.
干预措施: CART-EGFR-IL13Ra2 T cells (Biological)
Arm A
Subjects will receive a single fixed-dose administration of CART-EGFR-IL13Ra2 cells following lymphodepletion.
干预措施: CART-EGFR-IL13Ra2 T cells (Biological)
结局指标
主要结局
Number of Subjects with treatment related adverse events using NCI Common Terminology Criteria for Adverse Events (CTCAE) V5.0
时间窗: Up to 15 years following CART-EGFR-IL13Ra2 administration
Type, frequency, severity, and attribution of adverse events
Occurrence of treatment-limiting toxicities (Arms A and B only)
时间窗: Up to 28 days following CART-EGFR-IL13Ra2 administration
Type, frequency, severity, and attribution of treatment limiting adverse events as defined in protocol section 8.1.7
次要结局
- Duration of response (DOR)(Up to 15 years following CART-EGFR-IL13Ra2 administration)
- Evaluate the feasibility of different approaches for CART-EGFR-IL13Ra2 dosing(Up to 2 years)
- Progression-free Survival (PFS)(Up to 15 years following CART-EGFR-IL13Ra2 administration)
- Overall Survival (OS)(Up to 15 years following CART-EGFR-IL13Ra2 administration)
- Objective Response Rate (ORR)(Up to 15 years following CART-EGFR-IL13Ra2 administration)
- Evaluate the feasibility of different approaches for CART-EGFR-IL13Ra2 dosing(Up to 2 years)
- Progression-free Survival (PFS)(Up to 15 years following CART-EGFR-IL13Ra2 administration)
- Overall Survival (OS)(Up to 15 years following CART-EGFR-IL13Ra2 administration)
- Objective Response Rate (ORR)(Up to 15 years following CART-EGFR-IL13Ra2 administration)
- Duration of response (DOR)(Up to 15 years following CART-EGFR-IL13Ra2 administration)