RATIONALE: Vaccines made from a person's tumor cells and 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 of vaccine therapy in treating patients undergoing surgery for recurrent glioblastoma multiforme (GBM).

OBJECTIVES:

Primary

• To evaluate the feasibility and safety of an autologous brain tumor stem cell messenger ribonucleic acid (mRNA)-loaded dendritic cell vaccine in adult patients with recurrent glioblastoma multiforme.

Secondary

• To assess humoral and cellular immune responses to vaccination.
• To compare the proportion of vaccinated patients alive at 6 months from the time of surgery for recurrent tumor with matched historical cohorts.

OUTLINE: Patients undergo surgical resection of tumor. Tumor tissue samples are collected to isolate brain tumor stem cells (BTSCs) and for extraction and amplification of BTSC-specific mRNA. Within 4 weeks after surgical resection, patients undergo leukapheresis over 4 hours to generate dendritic cells (DCs). Patients also undergo leukapheresis at 1 week after the third vaccination and then at least every 3 months as needed for generation of additional DCs.

Patients receive autologous BTSC mRNA-loaded DC vaccine intradermally once weekly for 3 weeks and then once monthly in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

Inclusion Criteria:

• Age >18 years of age
• First recurrence of GBM (WHO Grade IV glioma or astrocytoma) in surgically accessible areas with prior histologic diagnosis of GBM
• No known contraindications to receiving Avastin
• Karnofsky Performance Status (KPS) of > 70%
• Radiation Therapy (RT) with ≥ 45 Gy tumor dose, completed ≥ 8 weeks prior to study entry

Exclusion Criteria:

• Contrast-enhancing tumor component crossing the midline, multi-focal tumor, or tumor dissemination (subependymal or leptomeningeal)
• Clinically significant increased intracranial pressure (e.g., impending herniation), uncontrolled seizures, or requirement for immediate palliative treatment
• Pregnant or need to breast feed during the study period (Negative beta-human chorionic gonadotropin (HCG) test required), or unable to maintain use of contraception while on study
• Active infection requiring treatment or an unexplained febrile (> 101.5 degrees F) illness
• Known immunosuppressive disease, autoimmune disease or human immunodeficiency virus infection, Hepatitis B or Hepatitis C
• Unstable or severe intercurrent medical conditions such as severe heart (New York Association Class 3 or 4) or lung (FEV1 < 50%) disease, uncontrolled diabetes mellitus
• Prior brachytherapy, carmustine wafer therapy, radiolabeled monoclonal antibodies, or stereotactic radiosurgery
• Prior inguinal lymph node dissection

Avastin-Specific Exclusion Criteria

Subjects meeting any of the following criteria are ineligible for study entry:

• Inadequately controlled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure > 100 mmHg)
• Prior history of hypertensive crisis or hypertensive encephalopathy
• New York Heart Association (NYHA) Grade II or greater congestive heart failure
• History of myocardial infarction or unstable angina within 6 months prior to enrollment
• History of stroke or transient ischemic attack within 6 months prior to enrollment
• Significant vascular disease (e.g. aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) (within 6 months prior to enrollment)
• History of hemoptysis (> or = 1/2 teaspoon of bright red blood per episode) within 28 days prior to enrollment
• Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to enrollment
• Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to enrollment
• Serious, non-healing wound, active ulcer or untreated bone fracture
• Proteinuria as defined by > +1 on urinalysis dipstick
• Known hypersensitivity to any component of Avastin
• Pregnant (positive pregnancy test) or lactation