A Phase I Study of Anti-CD3 x Cetuximab-Armed Activated T Cells, Low Dose IL-2, and GM-CSF for EGFR-Positive, Advanced Non-Small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 5
- 试验地点
- 2
- 主要终点
- Determination of immunologic changes by evaluation of cytokine profiles obtained before and after stimulation with OKT3 in vitro
研究概览
简要总结
RATIONALE: Giving autologous lymphocytes that have been treated in the laboratory with antibodies may stimulate the immune system to kill tumor cells. Aldesleukin may stimulate the lymphocytes to kill tumor cells. Colony-stimulating factors, such as GM-CSF, may increase the number of immune cells found in bone marrow or peripheral blood. Giving laboratory-treated autologous lymphocytes together with aldesleukin and GM-CSF may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of laboratory-treated autologous lymphocytes when given together with aldesleukin and GM-CSF in treating patients with recurrent, refractory, or metastatic non-small cell lung cancer.
FUNDING SOURCE--FDA OOPD
详细描述
OBJECTIVES:
Primary
- Determine the safety and maximum tolerated dose of EGFRBi-armed autologous activated T-cells (ATC) when administered in combination with low-dose aldesleukin and sargramostim (GM-CSF) in patients with recurrent, refractory, or extensive (metastatic) non-small cell lung cancer (NSCLC).
Secondary
- Assess clinical outcome based on tumor responses, overall survival, and progression-free survival.
- Monitor changes in sera concentrations of the tumor marker in association with EGFRBi-armed ATC administration throughout the study and at time points thereafter in patients with elevated levels of carcinoembryonic antigen (CEA) prior to beginning the study.
- Monitor patient sera for human anti-mouse antibodies (HAMA).
- Evaluate immune response, which may reflect immune augmentation in response to EGFRBi-armed ATC infusions, in peripheral blood mononuclear cell (PBMC) samples as well as purified immune cell populations.
- Investigate proliferation in response to ex vivo stimulation with NSCLC tumor-associated antigens, sera cytokine profiles (Th1 vs Th2), cytotoxicity of patient PBMC, and interferon gamma ELISPOTS as a surrogate marker for assessing generation of EGFR-specific cytotoxic T-lymphocytes (CTL).
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
T-cells
EGFRBi-armed autologous activated T cells
干预措施: EGFRBi-armed autologous activated T cells (Biological)
结局指标
主要结局
Determination of immunologic changes by evaluation of cytokine profiles obtained before and after stimulation with OKT3 in vitro
时间窗: 4 weeks
Safety
时间窗: 4 weeks
Maximum tolerated dose of EGFRBi-armed autologous activated T-cells
时间窗: 4 weeks
次要结局
- Evaluation of tumor markers and human anti-mouse antibody responses as assessed by carcinoembryonic antigen (CEA) levels in serum samples and development of IgG and IgM anti-mouse antibody responses to the Bi-antibodies(4 weeks)
- Determination of immunologic changes by evaluation of peripheral blood lymphocytes(4 weeks)
- Determination of immunologic changes by evaluation of cytotoxic T-lymphocytes as measured by interferon gamma ELISPOTS directed at autologous tumor or lung cancer cell lines(4 weeks)
- Progression-free survival(2 years)
- Overall survival(2 years)
- Determination of immunologic changes by evaluation of phenotypes of peripheral blood mononuclear cells before and after immunotherapy(4 weeks)