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:

• 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