Clinical Study of an Dendritic and Glioma Cells Fusion Vaccine With IL-12 for Treatment-naïve GBM Patients.

Study Overview
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Brief Summary
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A multi-center, open-label, single-arm, phase I/II clinical study is designed to test the safety and immunogenicity of an investigational Dendritic and Glioma Cells Fusion vaccine given with IL-12 for treatment-naïve patients after resection of glioblastoma.

Detailed Description
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This clinical trail includes two phases: basic treatment phase and immunotherapy phase. In basic treatment phase, patients will receive concomitant radiation and TMZ-chemotherapy. In immunotherapy phase, besides maintenance chemotherapy with TMZ, Fusion cells will be administered with IL-12 to enhance the immunity of patients.

Official Title
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Clinical Study of an Dendritic and Glioma Cells Fusion Vaccine With IL-12 for Treatment-naïve GBM Patients.

Conditions
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Glioblastoma, Glioma, Neoplasms, Neuroepithelial, Neuroectodermal Tumors, Neoplasms, Neoplasms, Nerve Tissue, Vaccines, Immunologic Factors

Intervention / Treatment
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* Biological: Dendritic Cell/Tumor Fusion Vaccine
* Drug: Interleukin-12
* Drug: Temozolomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years; Male or Female. Treatment-naïve patients after Resection of Glioblastoma. Histologically confirmed Glioblastoma. KPS ≥ 60 White blood cell count (WBC) ≥ 3.0 x 109/L; peripheral blood lymphocyte (PBL) ≥ 25%. Echocardiographic assessment of left ventricular ejection fraction (LVEF) ≥ 40% within 1 month of enrollment. Patients must be able to understand the investigational nature of the study and provide informed consent. Exclusion Criteria: Those who are allergic constitution, or allergic to biological products, or have contraindications to CT and MRI1 contrast agents. Those with severe autoimmune diseases or immunodeficiency diseases. Those who are expected to take systemic corticosteroids within three months. Those who needs long-term usage of immunosuppressive agents. Those with infectious diseases, including syphilis, AIDS, hepatitis B, hepatitis C, etc. Those who plan to receive any other anti-tumor treatment during the trial. Combined with serious primary diseases of cardiovascular, liver and kidney, and liver function (ALT, AST, Y-GT) exceeding 1.5 times of the upper limit: BUN or Cr exceeding 1.5 times of the upper limit of normal value. Patients with other malignant tumors. Those with active infections, etc. Suspected or confirmed a history of alcohol and drug abuse. Psychiatric illness, intellectual and language disabilities that compromise the informed consent process, at the discretion of the investigator. Women who are pregnant or nursing. Women of childbearing age who refuse to contraception. Active participation in another clinical treatment trials. According to the judgment of the investigator, other conditions that the plan cannot be followed.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Safety Evaluation Group<br>Basic treatment phase: The patients have surgery followed by concomitant radiation (2 Gy/day x 30 days) and TMZ-chemotherapy (75 mg/m2/ day x 42 days). Immunotherapy phase: Maintenance chemotherapy with TMZ will be administered at 150-200 mg/m2/day for 5 days in each 28-day cycle. Fusion cells will be suspended in 0.5 mL normal saline and then injected intradermally close to a cervical lymph node. IL-12 will be injected subcutaneously at the same side at dose of 6ug twice for interval of one hour. | Biological: Dendritic Cell/Tumor Fusion Vaccine<br>* Vaccine is derived from the participants dendritic cells and tumor cells.<br>* Other names: DC/tumor cell fusion vaccine;Drug: Interleukin-12<br>* Given subcutaneously at dose of 6ug twice for interval of one hour.<br>* Other names: IL-12;Drug: Temozolomide<br>* Following concomitant radiation (2 Gy/day x 30 days) and TMZ-chemotherapy (75 mg/m2/ day x 42 days) , maintenance chemotherapy with TMZ will be administered at 150-200 mg/m2/day for 5 days in each 28-day cycle.<br>* Other names: TMZ;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events (AE) / Serious Adverse Events (SAE) | AE/SAE associated with the intervention will be captured throughout the treatment portion of the study. All adverse events will be then compiled and these patients will be recorded. | 2-3 years | 
| Progression free survival (PFS) at 6 months | Assessed from this study start date to the date of the first observation of clinical or radiographic disease progression or death due to any cause. Patients will be censored at the time they are last known to be alive and progression free (if withdrawn or lost to follow-up). | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunological Assays | Assays including Flow Cytometry and Elispot will be employed to determine if cellular and humoral immunity were induced by serial vaccination with DC/Tumor Fusion Cells and IL-12. | 2-3 years | 
| Overall survival (OS) time | Assessed from this study start date to date of death of any cause. Patients will be censored at the time that they are last known to be alive (if withdrawn or lost to follow-up). | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 120 months |