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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Standard of Care | Active Comparator | Subjects will have standard surgery which will be followed approximately 5 weeks later by combined radiotherapy and chemotherapy consisting of temozolomide 75 mg/m2 dosed once daily beginning on the first day of radiotherapy and continuing until the final day of radiotherapy. Subjects will receive adjuvant temozolomide, and proceed with post therapy surveillance. |
|
| Interventional TVI-Brain-1 Autologous Vaccine and activated autologous blood-derived t cells | Experimental | TVI-Brain-1 immunotherapy is integrated with radiation and temozolomide in the test group in the following manner: 1) Subjects undergo surgical resection of their cancer and are tapered off steroids. 2) Subjects receive the first vaccination of TVI-Brain-1 as soon as the laboratory prepared vaccine is available for use (approximately 7 - 14 days following surgery). 3) Subjects receive a second vaccination 7-10 days later. 4) Subjects are leukapheresed to obtain immune T cells for ex vivo-activation. 5) Subjects' T cells are stored frozen until after chemoradiotherapy is completed. 6) Following chemoradiotherapy Subjects are infused with activated effector T cells followed by a 10-day course of low-dose interleukin 2 (IL-2). 7) Subjects then proceed with post therapy surveillance. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TVI-Brain-1 | Biological | Attenuated autologous cancer cells and activated autologous blood-derived t cells |
|
| Measure | Description | Time Frame |
|---|---|---|
| Survival | All Subjects will be evaluated and contacted to evaluate their status | From date of randomization until the date of death from any cause assessed up to 24 months after randomization. |
| Measure | Description | Time Frame |
|---|---|---|
| Progression-free survival | 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 | From date of randomization until the date of first documented progression assessed up to 24 months after randomization |
| Measure | Description | Time Frame |
|---|---|---|
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | Assessment of changes in patient through Physical Examination | Through study completion, an average of 2 years |
| Immunogenicity |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jean Aguiar, APRN | TVAX Biomedical, Inc | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Center for Neurosciences | Tucson | Arizona | 85718 | United States | ||
| Cedar-Sanai Medical Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 1407433 | Background | Holladay FP, Heitz T, Chen YL, Chiga M, Wood GW. Successful treatment of a malignant rat glioma with cytotoxic T lymphocytes. Neurosurgery. 1992 Sep;31(3):528-33. doi: 10.1227/00006123-199209000-00015. | |
| 1403119 | Background | Holladay FP, Heitz T, Wood GW. Antitumor activity against established intracerebral gliomas exhibited by cytotoxic T lymphocytes, but not by lymphokine-activated killer cells. J Neurosurg. 1992 Nov;77(5):757-62. doi: 10.3171/jns.1992.77.5.0757. |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| ICF | No | No | Yes | Informed Consent Form | Sep 16, 2022 | Dec 22, 2022 |
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Blinded over-read of sequential MRI assessments
| Standard of Care | Procedure | Surgery for tumor removal or debulking to minimize tumor burden |
|
| Radiotherapy | Radiation | 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. |
|
| Temozolomide | Drug | 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 . |
|
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Delayed-type hypersensitivity (DTH) skin testing using attenuated autologous cancer cells will be performed to assess the immunogenicity of the Subject's cancer.
| Assessed at 24 hours after each vaccine administration |
| Other genetic and immunologic parameters | 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 | Assessed at 24 hours after each vaccine administration |
| Los Angeles |
| California |
| 90048 |
| United States |
| University of Southern California Keck School of Medicine | Los Angeles | California | 90048 | United States |
| Moffitt Cancer Center | Tampa | Florida | 33612 | United States |
| Aaron Mammoser | Atlanta | Georgia | 30309 | United States |
| University of Kansas Medical Center | Kansas City | Kansas | 66061 | United States |
| Capital Health | Pennington | New Jersey | 08534 | United States |
| Providence St. Vincent | Portland | Oregon | 97225 | United States |
| 9225000 | Background | Plautz GE, Touhalisky JE, Shu S. Treatment of murine gliomas by adoptive transfer of ex vivo activated tumor-draining lymph node cells. Cell Immunol. 1997 Jun 15;178(2):101-7. doi: 10.1006/cimm.1997.1140. |
| 16817692 | Background | Sloan AE, Dansey R, Zamorano L, Barger G, Hamm C, Diaz F, Baynes R, Wood G. Adoptive immunotherapy in patients with recurrent malignant glioma: preliminary results of using autologous whole-tumor vaccine plus granulocyte-macrophage colony-stimulating factor and adoptive transfer of anti-CD3-activated lymphocytes. Neurosurg Focus. 2000 Dec 15;9(6):e9. doi: 10.3171/foc.2000.9.6.10. |
| 10570748 | Background | Wood GW, Turner T, Wang YY, Holladay FP. Immune rejection of intracerebral gliomas using lymphocytes from glioma-bearing rats. J Immunother. 1999 Nov;22(6):497-505. doi: 10.1097/00002371-199911000-00004. |
| ICF_000.pdf |
| ID | Term |
|---|---|
| D059039 | Standard of Care |
| D011878 | Radiotherapy |
| D000077204 | Temozolomide |
| D004358 | Drug Therapy |
| ID | Term |
|---|---|
| D019984 | Quality Indicators, Health Care |
| D011787 | Quality of Health Care |
| D006298 | Health Services Administration |
| D017530 | Health Care Quality, Access, and Evaluation |
| D013812 | Therapeutics |
| D003606 | Dacarbazine |
| D014226 | Triazenes |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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