Glioblastoma
Conditions
Keywords
Glioblastoma, DC vaccine, tumor antigen, personalized vaccine
Brief summary
Dendritic cell-based cellular vaccine for tumor therapy has shown efficacy. This study is designed to perform a personalized clinical trial by first analyzing the expression of tumor associated antigens in patients with newly diagnosed glioblastoma and then immunizing the patients with personalized DC-based cellular vaccine. Immune responses to tumor antigens will be monitored. Safety and efficacy will be observed in the study.
Detailed description
This is an open label, single-arm, single-institution, Phase I study designed to investigate the safety and efficacy of personalized cellular tumor vaccine for patients with newly diagnosed glioblastoma (GBM). Newly diagnosed GBM patients will undergo tumor resection. The tumors will be analyzed for the expression of a panel of glioma-associated antigens and immune-related genes. Post surgical treatment will be 6 weeks standard chemotherapy with temozolomide and concurrent radiotherapy and continue cycles of temozolomide within a 28-day window. Patients will undergo leukapheresis either after surgery or after concurrent radio/chemotherapy. Based on individual tumor antigen expression, in vitro transcribed mRNA will be generated and used to pulse in vitro generated DCs. The patients will be immunized i.d. and i.v. biweekly with DC cellular vaccines. Safety and efficacy will be monitored. The primary objective is to assess the safety of the personalized cellular vaccines. The secondary objective is to assess the specific T cell response to immunized vaccines. In addition, the antitumor efficacy of the vaccines will be measured using iRANO criteria, progression-free survival and overall survival.
Interventions
BIOLOGICALPersonalized cellular vaccine
Biological: DC-based cellular vaccine. Subjects will undergo surgical resection and standard 6-week chemo/radiotherapy and cycles of TMZ treatment. They will receive biweekly cellular vaccines.
Sponsors
Jinan University Guangzhou
Beijing Tricision Biotherapeutics Inc
Zhuhai Trinomab Pharmaceutical Co., Ltd.
Guangdong 999 Brain Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Newly diagnosed glioblastoma grade IV * Patients at the age of 18-65. * Patients must have undergone maximal surgical resection of the tumor. * Patients with Karnofsky scores \> or =70 * Patients with normal range of hematologic and metabolic test results. * Patients must have no corticosteroids treatment at least one week before vaccination. * Patients capable of understanding the study and signed informed consent.
Exclusion criteria
* Breast feeding females. * Pregnant women. * Infectious diseases HIV, HBV, HCV * Documented immunodeficiency * Documented autoimmune disease * Any serious or uncontrolled medical or psychiatric conditions, for example, severe pulmonary, cardiac or other systemic disease. * Patient inability to participate as determined by PI discretion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of treatment-emergent adverse events and severe adverse events [safety and Tolerability] | 3 years since the beginning of the first vaccine | Incidence of adverse events and severe adverse events to measure safety and tolerability of mRNA-TAA pulsed autologous DC cellular vaccine |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Antitumor antigen specific T cell response | 4 weeks after the last vaccine | The frequency of peripheral CD8+ and CD4+ T cell response to the vaccine. |
| Progression-free survival | 12 months since the beginning of the first vaccine. | Progression-free survival will be monitored for 1year. |
| Overall survival | 3 years since the beginning of the first vaccine | Overall survival will be monitored for 3 years. |
Countries
China
Outcome results
None listed