Phase I Study of Glioma-Associated Antigen (GAA) Peptide-pulsed Dendritic Cell Vaccination in Malignant Glioma Patients
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 8
- 试验地点
- 2
- 主要终点
- Tumor progression
研究概览
简要总结
RATIONALE: Vaccines made from peptides and a person's dendritic cells may help the body build an effective 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 dendritic cells pulsed with synthetic glioma-associated antigen (GAA) peptides in patients with malignant gliomas.
- Determine survival, tumor progression, and cellular immune response in patients treated with this regimen.
OUTLINE: 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 (IL-4), matured with a cytokine cocktail, and pulsed with synthetic glioma-associated antigen (GAA) peptides. Cohorts of patients receive escalating doses of GAA peptide-pulsed autologous dendritic cell vaccine until the maximum tolerated dose is determined.
After completion of study treatment, patients are followed every 2 months for 1 year.
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
- •Histologically confirmed diagnosis of 1 of the following malignant gliomas:
- •Anaplastic astrocytoma
- •Glioblastoma multiforme
- •Oligodendroglioma
- •Oligoastrocytoma
- •WHO grade III or IV disease
- •Newly diagnosed or recurrent disease
- •Bidimensionally measurable disease by contrast-enhancing MRI
- •Surgically accessible tumor for which resection is indicated
- •Previously treated with or planning to undergo treatment with conventional external beam radiotherapy
- •HLA-A*201 positive
- •Karnofsky performance status 60-100%
- •Life expectancy ≥ 8 weeks
- •Hemoglobin ≥ 10 g/dL
- •Absolute granulocyte count ≥ 1,500/mm³
- •Platelet count ≥ 100,000/mm³
- •SGOT and SGPT ≤ 2 times normal
- •Alkaline phosphatase ≤ 2 times normal
- •Bilirubin ≤ 1.5 mg/dL
- •BUN ≤ 1.5 times normal OR creatinine ≤ 1.5 times normal
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •Hepatitis B negative
- •Hepatitis C negative
- •HIV negative
- •Syphilis serology negative
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
- •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
- •prior chemotherapy (6 weeks for nitrosoureas) within last 4 weeks of starting treatment
- •concurrent corticosteroids within 2 weeks prior to treatment
- •radiotherapy within 2 weeks prior to treatment
- •systemic antibiotics within 72 hours prior to treatment
- •prior organ allograft
- •antihistamine therapy within 5 days before or after administration of study vaccine
- •chemotherapy during and for 4 weeks after administration of study vaccine
- •adjuvant therapy during and for 4 weeks after administration of study vaccine
- •other concurrent investigational agents
结局指标
主要结局
Tumor progression
时间窗: 1 year
Dose-limiting toxicity and maximum tolerated dose of autologous dendritic cells pulsed with synthetic glioma-associated antigen (GAA) peptides
时间窗: 3 months
Survival
时间窗: 1 year
次要结局
未报告次要终点