NCT03726515已完成1 期
Phase 1 Study of EGFRvIII-Directed CAR T Cells Combined With PD-1 Inhibition in Patients With Newly Diagnosed, MGMT-Unmethylated Glioblastoma
适应症
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 7
- 试验地点
- 2
- 主要终点
- Number of subjects with treatment-related adverse events, using NCI CTCAE v5.0.
研究概览
简要总结
This is an open-label, phase 1 study to assess the safety and tolerability of EGFRvIII T cells in combination with pembrolizumab (PD-1 Inhibitor) in patients with newly diagnosed, EGFRvIII+, MGMT-unmethylated glioblastoma.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •One of the following diagnoses of GBM:
- •a. Newly diagnosed glioblastoma multiforme that is histologically confirmed by pathology review of surgically resected tissue; OR b. An integrated molecular/pathologic diagnosis of diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, WHO grade IV. This diagnosis requires patients have one of the following: i. High-level amplification of EGFR; OR ii. Combined whole chromosome 7 gain and whole chromosome 10 loss (+7/-10); OR iii. TERT promoter mutation.
- •Undergone tumor resection.
- •No prior systemic therapies, radiation, tumor-treating fields, or intratumoral therapeutic agents including Gliadel wafers are allowed. Tumor resection must be the only tumor-directed treatment that the patient has received for glioboblastoma.
- •Tumor tissue is positive for EGFRvIII expression, as performed by either the University of Pennsylvania's in-house fusion transcript panel (RNA-based assay using Illumina HiSeq platform) or NeoGenomics Laboratories (quantitative RT-PCR assay).
- •Tumor tissue is negative for MGMT promoter methylation (i.e. the tumor is MGMT-unmethylated), as performed by either the University of Pennsylvania's in-house pyrosequencing protocol or NeoGenomics Laboratories.
- •Patients ≥ 18 years of age
- •ECOG performance status 0-1
- •Provides written informed consent
- •Must have adequate organ function as measured by:
- •White blood count ≥ 2500/mm3; platelets ≥ 100,000/mm3, hemoglobin ≥ 9.0 g/dL; without transfusion or growth factor support
- •AST, ALT, LDH, alkaline phosphatase within 2.5 x upper normal limit, and total bilirubin ≤ 2.0 mg/dL
- •Serum creatinine < 1.5 x upper limit of normal
- •Adequate cardiac function (LVEF ≥ 45%)
- •Subjects of reproductive potential must agree to use acceptable birth control methods.
排除标准
- •Pregnant or lactating women
- •Inadequate venous access for or contraindications to leukapheresis.
- •Active Hepatitis B, hepatitis C, or HIV infection, or other active, uncontrolled infection
- •History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40)
- •History of severe hypersensitivity reactions to other monoclonal antibodies which in the opinion of the investigator may post an increased risk of serious infusion reactions.
- •Requirement for immunosuppressive agents including but not limited to cyclosporine, MMF, tacrolimus, rapamycin, or anti-TNF agents within 4 weeks of eligibility confirmation by the physician-investigator.
- •Subjects with a history of known or suspected, severe or uncontrolled autoimmune or connective tissue disease. Patients with vitiligo, controlled type 1 diabetes mellitus (on stable insulin dose), residual autoimmune-related hypothyroidism (due to autoimmune condition only requiring hormone replacement), or psoriasis (not requiring systemic treatment), or conditions not expected to recur in the absence of an external trigger, are permitted to enroll.
- •Known history or current interstitial lung disease or non-infectious pneumonitis
- •Prior allogenic bone marrow or solid organ transplant
- •Any uncontrolled active medical or psychiatric disorder that would preclude participation as outlined.
- •Severe, active co-morbidity in the opinion of the physician-investigator would preclude participation in this study, including but not limited to the following:
- •Unstable angina within 6 months prior to eligibility confirmation by the physician-investigator
- •Transmural myocardial infarction within the last 6 months prior to eligibility confirmation by the physician-investigator
- •New York Heart Association grade II or greater congestive heart failure requiring hospitalization within 12 months prior to eligibility confirmation by the physician-investigator.
- •Serious and inadequately controlled cardiac arrhythmia
- •Serious or non-healing wound, ulcer, or history of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to eligibility confirmation by the physician-investigator, with the exception of the craniotomy for tumor resection.
- •Patients with tumors primarily localized to the brain stem or spinal cord.
结局指标
主要结局
Number of subjects with treatment-related adverse events, using NCI CTCAE v5.0.
时间窗: 15 Years
次要结局
- Progression-free survival (PFS)(15 Years)
- Overall survival Rate(15 Years)
- Objective response rate (ORR)(15 Years)
研究者
研究点 (2)
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