Pilot Feasibility and Safety Study of Cellular Immunotherapy for Recurrent/Refractory Malignant Glioma Using Genetically-Modified Autologous CD8+ T Cell Clones
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 3
- 主要终点
- Feasibility
研究概览
简要总结
RATIONALE: Cellular adoptive immunotherapy may stimulate the immune system in different ways and stop cancer cells from growing.
PURPOSE: This clinical trial is studying the side effects of cellular adoptive immunotherapy using genetically modified T-lymphocytes and to see how well it works in treating patients with recurrent or refractory high-grade malignant glioma.
详细描述
OBJECTIVES:
Primary
- To assess the feasibility and safety of cellular immunotherapy utilizing ex vivo expanded autologous CD8-positive T-cell clones genetically modified to express the IL-13 zetakine chimeric immunoreceptor and the Hy/TK selection/suicide fusion protein in patients with recurrent or refractory, high-grade malignant glioma.
Secondary
- To evaluate the antitumor activity of adoptively transferred clones in these patients.
- To screen for the development of anti-IL13 zetakine and anti-HyTK immune responses in these patients.
- To evaluate the efficacy of ganciclovir administration for ablating transferred clones in vivo should toxicity be encountered.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed malignant glioma at original diagnosis
- •Grade III or IV disease
- •Refractory or recurrent disease
- •Unifocal site of original disease in cerebral cortex
- •No clinical evidence of progressive encephalopathy
- •Has not undergone recent re-resection of recurrent or progressive disease
- •No communication between the tumor resection cavity and the ventricles and deep cerebrospinal fluid pathways as documented by post-operative MRI scan
- •PATIENT CHARACTERISTICS:
- •Karnofsky performance status 70-100%
- •Life expectancy > 3 months
- •WBC ≥ 2,000/dL
- •ANC > 1,000/dL
- •Platelet count ≥ 100,000/dL (unsupported by transfusion or growth factor)
- •Creatinine < 1.6 mg/dL
- •Bilirubin < 1.5
- •SGOT and SGPT < 2 times upper limit of normal
- •Not pregnant
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •Able to understand protocol basic elements and/or risks/benefits of participating in this pilot study
- •No requirement for supplemental oxygen to keep saturation > 95% that is not expected to resolve within 2 weeks
- •No uncontrolled cardiac arrhythmia
- •No hypotension requiring pressor support
- •No renal dialysis dependency
- •No refractory seizure disorder
- •No concurrent non-malignant illness that is poorly controlled with treatment or is of such severity the investigators deem it unwise to enter the patient on protocol
- •No severe infection for which patient is being treated
- •No history of ganciclovir and/or Prohance contrast allergy or intolerance
- •No HIV positivity within the past 3 months
- •PRIOR CONCURRENT THERAPY:
- •See Disease Characteristics
- •Must have recovered from major surgery
- •At least 4 weeks since primary therapy and no steroid dependence
- •At least 2 weeks since prior adjuvant cytotoxic chemotherapy and recovered
- •No concurrent systemic corticosteroids, except for use in managing T-cell therapy toxicity
- •No concurrent immunotherapy (i.e., interferons, vaccines, or other cellular products)
- •No concurrent pentoxifylline
- •No other concurrent investigative agents
- •No concurrent ganciclovir or ganciclovir derivative
- •No concurrent acyclovir for non-life threatening herpes virus infection
排除标准
- 未提供
研究组 & 干预措施
Treatment (therapeutic autologous lymphocytes)
Patients receive an infusion of autologous antigen-specific CD8+ cytotoxic T-lymphocyte clones over 5-10 minutes on days 1, 3, and 5 of weeks 1 and 2. Treatment repeats every 3 weeks for a total of 2 courses in the absence of disease progression or unacceptable toxicity.
干预措施: therapeutic autologous lymphocytes (Biological)
Treatment (therapeutic autologous lymphocytes)
Patients receive an infusion of autologous antigen-specific CD8+ cytotoxic T-lymphocyte clones over 5-10 minutes on days 1, 3, and 5 of weeks 1 and 2. Treatment repeats every 3 weeks for a total of 2 courses in the absence of disease progression or unacceptable toxicity.
干预措施: gene expression analysis (Genetic)
Treatment (therapeutic autologous lymphocytes)
Patients receive an infusion of autologous antigen-specific CD8+ cytotoxic T-lymphocyte clones over 5-10 minutes on days 1, 3, and 5 of weeks 1 and 2. Treatment repeats every 3 weeks for a total of 2 courses in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Feasibility
时间窗: 1 year after the end of treatment on study
Safety
时间窗: 1 year after the end of treatment on study
次要结局
- Anti-tumor activity of adoptively transferred clones(1 year after the end of treatment on study)
- Efficacy of ganciclovir for clone ablation (in the event of toxicity)(1 year after the end of treatment on study)
- Anti-IL 13 zetakine and anti-HyTK immune response in patients(1 year after the end of treatment on study)