Vaccine Therapy in Treating Patients Undergoing Surgery for Recurrent Glioblastoma Multiforme

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