Glioblastoma Multiforme of Brain
Conditions
Brief summary
This randomized study is designed to compare the combination of TVI-Brain-1 immunotherapy and standard therapy compared to standard therapy alone as a treatment for newly diagnosed MGMT unmethylated glioblastoma patients. The patients' own cancer cells collected after surgery are combined into a vaccine to produce an immune response that significantly increases the number of cancer neoantigen-specific effector T cell precursors in the patient's body. These cancer neoantigen-specific T cells are harvested from the blood, subsequently stimulated and expanded, and infused back into the patient.
Detailed description
This randomized study is designed to compare the combination of TVI-Brain-1 immunotherapy and standard therapy compared to standard therapy alone as a treatment for newly diagnosed MGMT unmethylated glioblastoma patients. The general procedures include the collection and testing of cancer tissue samples after surgery and chemoradiation therapy (radiation and temozolomide). For the patients randomized into the investigational study treatment group, they will also receive two vaccinations created from their own cancer cells, undergo leukapheresis to collect immune T-cells from their blood, and transfer of those activated effector T-cells after chemoradiation therapy. All patients are followed with MRIs at follow-up visits.
Interventions
BIOLOGICALTVI-Brain-1
Attenuated autologous cancer cells and activated autologous blood-derived t cells
PROCEDUREStandard of Care
Surgery for tumor removal or debulking to minimize tumor burden
RADIATIONRadiotherapy
Conformal radiotherapy consists of fractionated focal irradiation at a dose of 2 Gy per fraction given once daily five days per week (Monday through Friday) over a period of six weeks.
DRUGTemozolomide
All Subjects receive 75 mg/m2 of temozolomide daily beginning on the first day of radiotherapy and continuing until the completion of radiotherapy. Standard of care Subjects will also receive adjuvant temozolomide .
Sponsors
TVAX Biomedical
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Blinded over-read of sequential MRI assessments
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Newly diagnosed MGMT unmethylated glioblastoma multiforme (no prior treatment) * Sufficient cancer tissue obtained to allow for manufacture of autologous cancer cell vaccines * The attenuated autologous cancer cell product generated has satisfied the product release criteria as determined by the sponsor quality control department * Medical history, physical examination and laboratory testing performed within approximately 7 days before enrollment revealing kidney and liver organ function within normal limits * not currently receiving glucocorticoids and have been off glucocorticoids for at least 24 hours prior to vaccination as well as when they receive the T cell infusion. * Patient function assessment (Karnofsky score is \> 60) * a life expectancy of \> 12 weeks. * Hemoglobin is \> 10 g/dL (may be transfused) * White blood cell count is \> 3,000 cells/microliter (mcL) of blood. * Platelet count is \> 100,000 platelets per mcL of blood (transfusion independent) * Lymphocyte count is \> 1,000 cells/mcL of blood.
Exclusion criteria
* another concomitant life-threatening disease (not including glioblastoma multiforme) * a second malignancy that is not in remission as determined by the clinical investigator. Exception: squamous or basal cell carcinoma of the skin. * requirement for treatment with glucocorticoids to control brain swelling * presence of active autoimmune disease that is currently being actively treated. * psychological, familial, sociological or geographical conditions that do not permit adequate medical follow-up and compliance with the study protocol. * Current pregnancy or a plan to become pregnant within 1-year following the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Survival | From date of randomization until the date of death from any cause assessed up to 24 months after randomization. | All Subjects will be evaluated and contacted to evaluate their status |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival | From date of randomization until the date of first documented progression assessed up to 24 months after randomization | Time to progression is evaluated by review and analysis of serial MRI's taken at specific Time to progression is evaluated by review and analysis of serial MRI's taken at specific timepoints |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | Through study completion, an average of 2 years | Assessment of changes in patient through Physical Examination |
| Immunogenicity | Assessed at 24 hours after each vaccine administration | Delayed-type hypersensitivity (DTH) skin testing using attenuated autologous cancer cells will be performed to assess the immunogenicity of the Subject's cancer. |
| Other genetic and immunologic parameters | Assessed at 24 hours after each vaccine administration | The study is also designed to determine whether a wide variety of genetic and immunologic parameters that are monitored during and following treatment correlate with clinical outcomes |
Countries
United States
Outcome results
None listed