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