Phase I Dose Escalation Study of Autologous Tumor Lysate-Pulsed Dendritic Cell Immunotherapy for Malignant Gliomas
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- Dose Limiting Toxicity
研究概览
简要总结
RATIONALE: Vaccines made from a person's white blood cells mixed with tumor proteins may make the body build an immune response to kill tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of vaccine therapy in treating patients with malignant glioma.
详细描述
OBJECTIVES:
- Determine the dose-limiting toxicity and maximum tolerated dose of autologous tumor lysate-pulsed dendritic cells in patients with malignant gliomas.
- Determine survival, tumor progression, and cellular immune response in patients treated with this regimen.
OUTLINE: This is a dose-escalation study.
Patients undergo leukapheresis for the collection of peripheral blood mononuclear cells (PBMC). Autologous dendritic cells (DC) are prepared from autologous PBMC exposed to sargramostim (GM-CSF) and interleukin-4 and pulsed with autologous tumor lysate. Patients receive autologous tumor lysate-pulsed DC intradermally on days 0, 14, and 28 in the absence of unacceptable toxicity.
Cohorts of 6-12 patients receive escalating doses of autologous tumor lysate-pulsed DC until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
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
- •Eligibility Criteria:
- •Histologically confirmed diagnosis of one of the following malignant gliomas:
- •Anaplastic astrocytoma
- •Glioblastoma multiforme
- •Anaplastic oligodendroglioma
- •Malignant mixed oligoastrocytoma
- •WHO grade III or IV disease
- •Newly diagnosed disease
- •Bidimensionally measurable disease by contrast-enhancing MRI
- •Surgically accessible tumor for which resection is indicated
- •Previously treated with or plan to undergo treatment with conventional external beam radiotherapy
- •Age 18 and over
- •Performance status Karnofsky 60-100%
- •Life expectancy at least 8 weeks
- •Hemoglobin at least 10 g/dL
- •Absolute granulocyte count at least 1,500/mm^3
- •Platelet count at least 100,000/mm^3
- •SGOT and SGPT no greater than 2 times normal
- •Alkaline phosphatase no greater than 2 times normal
- •Bilirubin no greater than 1.5 mg/dL
- •Hepatitis B negative
- •Hepatitis C negative
- •BUN no greater than 1.5 times normal
- •Creatinine no greater than 1.5 times normal
- •HIV negative
- •Syphilis serology negative
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •At least 2 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered.
- •At least 2 weeks since prior corticosteroids
- •At least 2 weeks since prior radiotherapy and recovered
- •More than 72 hours since prior systemic antibiotics
排除标准
- •active infection
- •immunodeficiency
- •autoimmune disease that may be exacerbated by immunotherapy, including any of the following:
- •Rheumatoid arthritis
- •Systemic lupus erythematosus
- •Vasculitis
- •Polymyositis-dermatomyositis
- •Scleroderma
- •Multiple sclerosis
- •Juvenile-onset insulin-dependent diabetes
- •allergy to study agents
- •pregnant or nursing
- •underlying condition that would contraindicate study therapy
- •concurrent severe or unstable medical condition that would preclude giving informed consent
- •psychiatric condition that would preclude study participation or giving informed consent
- •other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, localized prostate cancer, or carcinoma in situ of the cervix
- •concurrent chemotherapy during and for 2 weeks after administration of study vaccine
- •concurrent corticosteroids prior organ allograft
- •antihistamine therapy within 5 days before or after administration of study vaccine
- •other concurrent investigational agents
- •concurrent adjuvant therapy during and for 2 weeks after administration of study vaccine
研究组 & 干预措施
autologous tumor lysate-pulsed DC
干预措施: therapeutic autologous dendritic cells (Biological)
结局指标
主要结局
Dose Limiting Toxicity
时间窗: 4 weeks
次要结局
- Time to tumor progression, overall survival and cellular immune responses in brain tumor patients injected with tumor lysate pulsed dendritic cells(2 years)