• Response [ Designated as safety issue: No ]
• Time to tumor progression [ Designated as safety issue: No ]
• Survival [ Designated as safety issue: No ]

• Response
• Time to tumor progression
• Survival

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.

DISEASE CHARACTERISTICS:

• 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

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 60-100%

Life expectancy

• At least 8 weeks

Hematopoietic

• Hemoglobin at least 10 g/dL
• Absolute granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• 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

Renal

• BUN no greater than 1.5 times normal OR
• Creatinine no greater than 1.5 times normal

Immunologic

• HIV negative
• Syphilis serology negative
• Afebrile
• No active infection
• No immunodeficiency

• No 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
• No allergy to study agents

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No underlying condition that would contraindicate study therapy
• No concurrent severe or unstable medical condition that would preclude giving informed consent
• No psychiatric condition that would preclude study participation or giving informed consent
• No 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 CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• At least 2 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered
• No concurrent chemotherapy during and for 2 weeks after administration of study vaccine

Endocrine therapy

• At least 2 weeks since prior corticosteroids
• No concurrent corticosteroids

Radiotherapy

• See Disease Characteristics
• At least 2 weeks since prior radiotherapy and recovered

Surgery

• See Disease Characteristics
• No prior organ allograft

Other

• More than 72 hours since prior systemic antibiotics
• No antihistamine therapy within 5 days before or after administration of study vaccine
• No other concurrent investigational agents
• No concurrent adjuvant therapy during and for 2 weeks after administration of study vaccine