Randomized Phase 2b Study of Safety And Efficacy Of TVI-Brain-1 Combined With Conformal Radiotherapy And Temozolomide Vs Standard Therapy In Newly Diagnosed MGMT Negative Glioblastoma Multiforme (GBM)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 120
- 试验地点
- 8
- 主要终点
- Survival
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
Blinded over-read of sequential MRI assessments
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Standard of Care
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.
干预措施: Standard of Care (Procedure)
Standard of Care
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.
干预措施: Radiotherapy (Radiation)
Standard of Care
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.
干预措施: Temozolomide (Drug)
Interventional TVI-Brain-1 Autologous Vaccine and activated autologous blood-derived t cells
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.
干预措施: TVI-Brain-1 (Biological)
Interventional TVI-Brain-1 Autologous Vaccine and activated autologous blood-derived t cells
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.
干预措施: Standard of Care (Procedure)
Interventional TVI-Brain-1 Autologous Vaccine and activated autologous blood-derived t cells
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.
干预措施: Radiotherapy (Radiation)
Interventional TVI-Brain-1 Autologous Vaccine and activated autologous blood-derived t cells
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.
干预措施: Temozolomide (Drug)
结局指标
主要结局
Survival
时间窗: 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
次要结局
- Progression-free survival(From date of randomization until the date of first documented progression assessed up to 24 months after randomization)