Study To Test the Safety and Efficacy of TVI-Brain-1 As A Treatment for Recurrent Grade IV Glioma

Study Overview
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Brief Summary
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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.

Detailed Description
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The TVI-Brain-1 treatment involves several steps. First, the patient's cancer will be surgically removed to provide cells for the vaccine. Second, the patient will be vaccinated with the vaccine formulation. Third, the patient's blood will be filtered for killer T cell precursors which will then be cultured and stimulated to reach a higher (killer) activity level. Fourth, the activated cells will be infused into the patient's bloodstream so that they will be able to attack the cancer.

Official Title
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Phase 2 Study To Test The Safety and Efficacy of TVI-Brain-1 As A Treatment For Recurrent Grade IV Glioma

Conditions
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Grade IV Glioma, Grade IV Astrocytoma, Glioblastoma Multiforme

Intervention / Treatment
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* Biological: TVI-Brain-1


Participation Criteria
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Eligibility Criteria
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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. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TVI-Brain-1<br>All patients will receive the full TVI-Brain-1 treatment. | Biological: TVI-Brain-1<br>* Following surgery, tumor tissue is used to generate a cancer vaccine. Patients are vaccinated with neutralized cells to initiate an immune response. Following vaccinations, the patient's white blood cells are collected, the white blood cells are stimulated and expanded, and are then reinfused into the patient's blood.<br>* Other names: Cancer vaccine plus immune adjuvant plus activated WBC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression of Disease | To assess the efficacy of TVI-Brain-1 on patients to evaluate progression free survival. MRI data is used to evaluate tumor progression; success is defined if a patient is still alive and has < 25 % increase in Tumor volume in MRI collected at 6 month timepoint. | 6-months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | All patients will be followed until death or the end of the study to measure overall survival. | 32 months | 
| Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | Toxicity will be assessed throughout the study by recording clinical symptoms, performing physical examinations, measuring vital signs and performing clinical laboratory tests, including complete blood counts and differentials, blood chemistries and autoimmune profiles. | 12 weeks | 
| Time to Progression of Tumor Per MRI | Time to progression is defined date of evidence of increase in tumor volume as evaluated by review and analysis of imaging, using MacDonald Criteria in review of serial MRI's taken at specific timepoints | 32-months | 
| Objective Response Rate | Time to progression is defined as assessed by neurologists and radiologists evaluation of time to worsening of patient's neurological status and/or increase in tumor volume measurements as evaluated by review and analysis of serial physical exams and MRI's taken at specific timepoints | 32-months | 
| Delayed-type Hypersensitivity (DTH) Skin Testing | Skin Test using attenuated autologous cancer cells will be performed to assess the immunogenicity of the Subject's cancer. Evidence of a Resulting wheal or flare reaction from sub-cutanous injection of test will be evaluated in each patient | 48 hours | 
| Quality of Life as Measured by FACT-Br Tool Score | Quality of life data using the FACT-Br score tabulation from responses on validated tool | 32 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Brain Neoplasms, Central Nervous System Neoplasms, Brain Diseases, Neoplasms, Nervous System Neoplasms, Glioblastoma, Astrocytoma, Nervous System Diseases, Central Nervous System Diseases, Glioma, Recurrent astrocytoma, Recurrent glioma, Cancer vaccine, Immunotherapy, Killer T cells, Activated T cells, GM-CSF, Activated lymphocytes