vaccine therapy in treating patients with malignant glioma

Conditions: Brain and Central Nervous System Tumors

Summary: 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.

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. patients are followed every 2 months for 2 years. projected accrual: a total of 3-18 patients will be accrued for this study within 9-18 months.

Eligibility criteria:
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 * afebrile * 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 exclusion criteria: * 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

Keywords: adult glioblastoma adult anaplastic astrocytoma adult brain tumor adult giant cell glioblastoma adult gliosarcoma adult anaplastic oligodendroglioma