Personalized Cellular Vaccine for Recurrent Glioblastoma (PERCELLVAC2)

Study Overview
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Brief Summary
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The treatment option for recurrent glioblastoma is limited. Immune cell based therapy for glioblastoma has shown some efficacy. This study is designed to perform a personalized clinical trial by first analyzing the expression of tumor associated antigens in patients with recurrent glioblastoma and then immunizing the patients with personalized antigen pulsed DCs. Immune responses to the immunized antigens will be monitored. Safety and efficacy will be observed in this study.

Detailed Description
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This is an open label, single-arm, single-institution, Phase I study designed to investigate the safety and efficacy of personalized cellular vaccines for patients with recurrent glioblastoma (GBM). Recurrent 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. Patients will undergo leukapheresis to collect mononuclear cells for DC generation. Based on the expression profiles of tumor-associated antigens, in vitro transcribed mRNA will be generated to pulse autologous DCs. Patients will be conditioned with immune adjuvants before and during immunization. Patients will receive biweekly vaccines. The antitumor specific T cell responses will be measured. Safety and efficacy will be monitored. The objective is to assess the safety of the personalized cellular vaccines and T cell responses. The efficacy of the vaccines will be evaluated using iRANO criteria, progression-free survival and overall survival.

Official Title
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Personalized Cellular Vaccine Therapy in Treating Patients With Recurrent Glioblastoma (PerCellVac2)

Conditions
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Glioblastoma

Intervention / Treatment
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* Biological: Personalized cellular vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Recurrent glioblastoma grade IV Patients at the age of 18-65. Patients undergo tumor resection. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Personalized cellular vaccine<br>Subjects will undergo tumor resection. They will receive biweekly cellular vaccines consisting of mRNA tumor antigen pulsed autologous DCs. | Biological: Personalized cellular vaccine<br>* Patients with recurrent glioblastoma will undergo tumor resection and receive tumor antigen pulsed cellular vaccines.<br>* Other names: Tumor antigen pulsed DC autologous cellular vaccine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events and severe adverse events (safety and tolerability) | Incidence of adverse events and severe adverse events to measure safety and tolerability of mRNA-TAA pulsed autologous DC, allogeneic PBMCs and autologous tumor cellular vaccines. | 3 years since the beginning of the first vaccine | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antitumor antigen specific T cell response | The frequency of the peripheral CD8+ and CD4+ T cell response to the vaccine will be measured. | 4 weeks after the last vaccine | 
| Progression-free survival | Progression-free survival will be monitored for 1 year. | 12 months since the beginning of the first vaccine | 
| Overall survival | Overall survival will be monitored for 3 years. | 3 years since the beginning of the first vaccine | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Recurrent glioblastoma, DC vaccine, tumor antigen, personalized vaccine