Clinical Trial Finder

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

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.

Arms

Experimental: BTSC mRNA-loaded DCs

BTSC mRNA-loaded DCs administered intradermally weekly for first 3 vaccines, then monthly until progression or withdrawal.

Interventions

Biological: - BTSC mRNA-loaded DCs

An escalating total dose of BTSC mRNA-loaded DCs (2x10^6, 5x10^6, and 2x10^7 per vaccination) will be evaluated for purpose of establishing a maximum tolerated dose (MTD) and a dose-limiting toxicity (DLT).