Phase I/II Study To Test The Safety and Efficacy of TVI-Brain-1 As A Treatment For Recurrent Grade IV Glioma

• Relative toxicity [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
  To determine the relative toxicity (safety) of vaccinating recurrent grade IV glioma patients four times with live, attenuated cancer cells combined with granulocyte-macrophage colony-stimulating factor (GM-CSF). Toxicity will be assessed following delivery of each treatment component.
• Progression free survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  Evaluate progression free survival at 6 months as a surrogate for overall survival.

• Immunogenicity [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  The potency of the modified vaccination regimen will be assessed by measuring immune responses following each vaccination. The study is designed to determine whether vaccinating recurrent grade IV glioma subjects four times with attenuated cancer cells stimulates more powerful immune responses than vaccinating subjects twice. Clinical effects also will be measured to determine whether the treatment causes the cancer to regress.
• Overall survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  Evaluate overall survival of patients

TVI-Brain-1 is an experimental treatment that takes advantage of the fact that your body can produce immune cells, called 'killer' white blood cells that have the ability to kill large numbers of the cancer cells that are present in your body. TVI-Brain-1 is designed to generate large numbers of those 'killer' white blood cells and to deliver those cells into your body so that they can kill your cancer cells.

TVI-Brain-1 involves several steps. First, the patient's cancer will be surgically removed to provide cells for the vaccine. Second, the patient will be vaccinated twice with those cells and GM-CSF. Third, the patient's blood will be filtered for white cells which will then be cultured and stimulated to reach a higher (killer) activity level. Fourth, the activated white blood cells will be infused into the patient's bloodstream so that they will be able to attack the cancer. Fifth, the patient will receive a course of low-dose interleukin-2 (IL-2), which stimulates the activated white blood cells to continue to multiply after they are in the body. Finally, the entire process starting with vaccination and ending with IL-2 injections will be repeated, for a total of two rounds of therapy.

• Glioma
• High Grade Astrocytoma
• Glioblastoma Multiforme

Inclusion Criteria:

• Age > 18
• Informed consent
• Diagnosis of grade IV glioma with progression following standard treatment.
• Must be able to tolerate surgery to provide tumor tissue for vaccine.
• Must be able to produce viable vaccine from tumor tissue.
• Eastern Cooperative Oncology Group (ECOG) performance status must be < 2 or Karnofsky Performance Status must be 70 or greater.
• Negative HIV test.
• Negative for hepatitis B and C virus.
• Respiratory reserve must be reasonable.
• Sufficient renal function.
• Satisfactory blood counts.
• Negative pregnancy test for women of childbearing potential.

Exclusion Criteria:

• Surgically removed cancer reveals that it is not grade IV glioma.
• Concomitant life-threatening disease.
• Active autoimmune disease.
• Currently receiving chemotherapy or biological therapy for the treatment of cancer.
• Currently receiving immunosuppressive drugs for any reason.
• Prior treatment with Avastin or other anti-angiogenesis treatment within 6 months.
• Prior treatment with Gliadel wafers.
• Corticosteroids beyond peri-operative period.
• Psychological, familial, sociological or geographical conditions that do not permit adequate medical follow-up and compliance with the study protocol.