NCT05063682Unknown1 期
A Phase 1 Study to Evaluate EGFRvIII -Targeted Chimeric Antigen Receptor (CAR) T Cells for Adult Patients With Leptomeningeal Glioblastoma
Chembrain LTD3 个研究点 分布在 2 个国家目标入组 10 人开始时间: 2020年5月15日最近更新:
适应症
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 10
- 试验地点
- 3
- 主要终点
- Incidence of adverse events
研究概览
简要总结
This phase I trial investigates the efficacy and safety of brain-targeting epidermal growth factor receptor chimeric antigen receptor immune cells (EGFRvIII-CAR T cells) in treating patients with leptomeningeal disease from glioblastoma. T cells are part of the immune system and help the body fight malignant tumours. Immune cells can be genetically modified to destroy brain tumor cells in the laboratory. EGFRvIII -CAR T cells are brain tumor specific and can enter and express its genes in immune cells. Administering patients EGFRvIII -CAR T cells may help to recognize and destroy brain tumor cells in patients with leptomeningeal disease from glioblastoma.
详细描述
PRIMARY OBJECTIVES:
- Examine and describe the safety and feasibility of EGFRvIII-specific hinge-optimized CD3 ζ-stimulatory/41BB-co-stimulatory Chimeric Antigen Receptor autologous T-lymphocytes (EGFRvIII -CAR T cells) through intracerebroventricular (ICV) delivery as adjuvant therapy in participants with EGFRvIII+ leptomeningeal disease from glioblastoma.
- Determine the activity of EGFRvIII -CAR T cells based on survival rate at 12 months for both arms.
SECONDARY OBJECTIVES:
- Describe persistence, expansion and phenotype of endogenous and EGFRvIII -CAR T cells in peripheral blood (PB), tumor cyst fluid (TCF) and cerebral spinal fluid (CSF) at applicable time points
- Describe cytokine levels in PB, TCF, and CSF at applicable time points
- Estimate the rate of disease response by Response Assessment in Neuro-Oncology Leptomeningeal Metastases (RANO LM) criteria
- Estimate rate of progression free survival at 6 months. Estimate rate of overall survival (OS) at 12 months by study arm.
- Estimate time to next treatment
- Evaluate EGFRvIII -CAR T cell persistence in the tumor tissue and the location of the EGFRvIII -CAR T cells with respect to the infusion site.
- Evaluate biomarkers and cytokine levels
OUTLINE:
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
- •Participant has been treated for leptomeningeal metastases after intrathecal chemotherapy and/or radiation OR refuses to undergo additional radiation and/or intrathecal chemotherapy
- •Participant must have a Karnofsky performance status (KPS) >= 60
- •Participant must have a life expectancy of >= 2 months
- •Women of child-bearing potential must have negative serum pregnancy test and agree to use a reliable form of birth control prior to study entry and for at least two months following study treatment. Male research participants must agree to use a reliable form of birth control and not donate sperm during the study and for at least two months following study treatment
- •Participant has a histologically confirmed EGFRvII+ (epidermal growth factor receptor) tumor expression by immunohistochemistry (IHC) at the initial tumor presentation or recurrent disease (H-score >= 50)
- •Participant or legal guardian must have the ability to understand and the willingness to sign a written informed consent
排除标准
- •Research participant requires supplemental oxygen to keep saturation greater than 95%
- •Research participant requires dialysis
- •Research participant has uncontrolled seizure activity and/or clinically evident progressive encephalopathy
- •Failure of research participant or legal guardian to understand the basic elements of the protocol and/or the risks/benefits of participating in the study.
- •Participant is unwilling to stop treatment with chemotherapy or endocrine therapy and/or radiation one week prior and during the first 4 cycles of the study
- •Participant has ventriculoperitoneal shunt
- •Participant has a coagulopathy or bleeding disorder
- •Participant is HIV+ (human immunodeficiency virus) or has acute CMV (cytomegalovirus) infection
- •Participant has any uncontrolled illness, including ongoing or active infection; participant has known active hepatitis B or C infection; participants with any signs or symptoms of active infection, positive blood cultures or radiological evidence of infections
- •Participant has an autoimmune disease that requires constant treatment
- •Participant has another active malignancy
- •Participant is unable to undergo a brain magnetic resonance imaging (MRI)
- •Participant is pregnant or breast feeding
结局指标
主要结局
Incidence of adverse events
时间窗: Up to 10 years
Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Overall survival
时间窗: 12 months
次要结局
- CAR (chimeric antigen receptor) T cell levels detected in tumor cyst fluid (TCF), peripheral blood (PB), and cerebrospinal fluid (CSF)(Up to 6 cycles (3 months), at the end of each cycle 1 (each cycle is 14 days))
- Endogenous T cell levels detected in tumor cyst fluid (TCF), peripheral blood (PB), and cerebrospinal fluid (CSF)(Up to 6 cycles (3 months), at the end of each cycle 1 (each cycle is 14 days))
- Cell phenotype detected in tumor cyst fluid (TCF), peripheral blood (PB), and cerebrospinal fluid (CSF)(Up to 6 cycles (3 months), at the end of each cycle 1 (each cycle is 14 days))
- Cytokine levels (Procartaplex panel) in PB, TCF and CSF(Up to 6 cycles (3 months), at the end of each cycle 1 (each cycle is 14 days))
- CAR T and endogenous cells detected in tumor tissue(Baseline and additional time points according to response (through study completion, up to 10 years by as needed basis))
- EGFRvII (epidermal growth factor receptor) antigen expression levels in tumor tissue.(Baseline and additional time points according to response (through study completion, up to 10 years by as needed basis))
- Disease response(Up to 10 years)
- Time to progression(Up to 10 years)
- Overall survival(Up to 10 years)
研究者
研究点 (3)
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