Glioblastoma Multiforme, Glioma, High Grade Astrocytoma
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, Low dose IL-2, 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
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. Finally, the entire process starting with vaccination will be repeated, for a total of two rounds of therapy.
Interventions
BIOLOGICALCancer vaccine plus immune adjuvant
Tumor tissue is used for cancer vaccine. Following vaccinations, white blood cells are collected, stimulated and expanded, and are then reinfused. The infusion is followed by a course of low-dose IL-2.
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. * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing the Incidence of Grade One or Higher Adverse Events | 8 weeks | 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. |
| Immunogenicity as Measured by Delayed Type Hypersensitivity Reactions | 48 hours | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 12 months | Evaluate overall survival of patients |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| TVI-Brain-1 Biological/Vaccine: Cancer vaccine plus immune adjuvant, plus activated white blood cells | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | TVI-Brain-1 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants |
| Age, Continuous | 60 years STANDARD_DEVIATION 10 |
| Region of Enrollment Latvia | 1 participants |
| Region of Enrollment United States | 11 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 12 / 12 |
| other Total, other adverse events | 12 / 12 |
| serious Total, serious adverse events | 12 / 12 |
Outcome results
Primary
Immunogenicity as Measured by Delayed Type Hypersensitivity Reactions
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.
Time frame: 48 hours
Population: Ten patients developed an immunological response to their tumor as indicated by the delayed type hypersensitivity immune test.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TVI-Brain-1 | Immunogenicity as Measured by Delayed Type Hypersensitivity Reactions | 10 Participants |
Primary
Number of Participants Experiencing the Incidence of Grade One or Higher Adverse Events
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.
Time frame: 8 weeks
Population: Number of participants that completed treatment protocol
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TVI-Brain-1 | Number of Participants Experiencing the Incidence of Grade One or Higher Adverse Events | 12 participants |
Secondary
Overall Survival
Evaluate overall survival of patients
Time frame: 12 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| TVI-Brain-1 | Overall Survival | 6.3 months |