Glioblastoma Multiforme, Grade IV Astrocytoma, Grade IV Glioma
Conditions
Keywords
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
Brief summary
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
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.
Interventions
BIOLOGICALTVI-Brain-1
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.
Sponsors
TVAX Biomedical
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression of Disease | 6-months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | 12 weeks | 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. |
| Time to Progression of Tumor Per MRI | 32-months | 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 |
| Overall Survival | 32 months | All patients will be followed until death or the end of the study to measure overall survival. |
| Delayed-type Hypersensitivity (DTH) Skin Testing | 48 hours | 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 |
| Quality of Life as Measured by FACT-Br Tool Score | 32 months | Quality of life data using the FACT-Br score tabulation from responses on validated tool |
| Objective Response Rate | 32-months | 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 |
Countries
United States
Participant flow
Recruitment details
The recruitment was prematurely closed to allow a change in protocol design based on clinical findings from the small study. The data justified change in protocol design (study #008) to treat subjects with minimal residual disease and healthy immune system.
Participants by arm
| Arm | Count |
|---|---|
| TVI-Brain-1 All patients will receive the full TVI-Brain-1 treatment.
TVI-Brain-1: 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. | 14 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lack of sufficient efficacy as patients were immunocompromised | 7 |
Baseline characteristics
| Characteristic | TVI-Brain-1 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 13 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 14 / 14 |
| other Total, other adverse events | 5 / 14 |
| serious Total, serious adverse events | 9 / 14 |
Outcome results
Primary
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.
Time frame: 6-months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TVI-Brain-1 | Progression of Disease | 14 Participants |
Secondary
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
Time frame: 48 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TVI-Brain-1 | Delayed-type Hypersensitivity (DTH) Skin Testing | 14 Participants |
Secondary
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.
Time frame: 12 weeks
Population: Toxicity was assessed throughout the study by recording clinical symptoms, physical examinations, vital signs, clinical laboratory tests, including blood counts and differentials, blood chemistries and autoimmune profiles. Patients were monitored for toxicities during the study and for one month following removal from the study for any reason.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TVI-Brain-1 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | 14 Participants |
Secondary
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
Time frame: 32-months
Population: MRI data not collected nor analyzed
Secondary
Overall Survival
All patients will be followed until death or the end of the study to measure overall survival.
Time frame: 32 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TVI-Brain-1 | Overall Survival | 0 Participants |
Secondary
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
Time frame: 32 months
Population: QOL tool data was not collected
Secondary
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
Time frame: 32-months
Population: MRI data not collected