vaccine therapy in treating patients with malignant glioma

Conditions: Brain and Central Nervous System Tumors

Summary: 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.

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.

Eligibility criteria:
inclusion criteria: * 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 * afebrile 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 * 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

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