Vaccine Therapy in Treating Patients With Malignant Glioma

Study Overview
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Brief Summary
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RATIONALE: Vaccines made from peptides and a person's dendritic cells may help the body build an effective immune response to kill tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of vaccine therapy in treating patients with malignant glioma.

Detailed Description
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OBJECTIVES: Determine the dose-limiting toxicity and maximum tolerated dose of autologous dendritic cells pulsed with synthetic glioma-associated antigen (GAA) peptides in patients with malignant gliomas. Determine survival, tumor progression, and cellular immune response in patients treated with this regimen. OUTLINE: Patients undergo leukapheresis for the collection of peripheral blood mononuclear cells (PBMC). Autologous dendritic cells (DC) are prepared from autologous PBMC exposed to sargramostim (GM-CSF) and interleukin-4 (IL-4), matured with a cytokine cocktail, and pulsed with synthetic glioma-associated antigen (GAA) peptides. Cohorts of patients receive escalating doses of GAA peptide-pulsed autologous dendritic cell vaccine until the maximum tolerated dose is determined. After completion of study treatment, patients are followed every 2 months for 1 year.

Official Title
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Phase I Study of Glioma-Associated Antigen (GAA) Peptide-pulsed Dendritic Cell Vaccination in Malignant Glioma Patients

Conditions
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Brain and Central Nervous System Tumors

Intervention / Treatment
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* Biological: glioma-associated antigen peptide-pulsed autologous dendritic cell vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed diagnosis of 1 of the following malignant gliomas: Anaplastic astrocytoma Glioblastoma multiforme Oligodendroglioma Oligoastrocytoma WHO grade III or IV disease Newly diagnosed or recurrent disease Bidimensionally measurable disease by contrast-enhancing MRI Surgically accessible tumor for which resection is indicated Previously treated with or planning to undergo treatment with conventional external beam radiotherapy HLA-A*201 positive Karnofsky performance status 60-100% Life expectancy ≥ 8 weeks Hemoglobin ≥ 10 g/dL Absolute granulocyte count ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ SGOT and SGPT ≤ 2 times normal Alkaline phosphatase ≤ 2 times normal Bilirubin ≤ 1.5 mg/dL BUN ≤ 1.5 times normal OR creatinine ≤ 1.5 times normal Negative pregnancy test Fertile patients must use effective contraception Hepatitis B negative Hepatitis C negative HIV negative Syphilis serology negative Afebrile Exclusion Criteria: active infection immunodeficiency autoimmune disease that may be exacerbated by immunotherapy, including any of the following: Rheumatoid arthritis Systemic lupus erythematosus Vasculitis Polymyositis-dermatomyositis Scleroderma Multiple sclerosis Juvenile-onset insulin-dependent diabetes allergy to study agents underlying condition that would contraindicate study therapy concurrent severe or unstable medical condition that would preclude giving informed consent psychiatric condition that would preclude study participation or giving informed consent other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, localized prostate cancer, or carcinoma in situ of the cervix prior chemotherapy (6 weeks for nitrosoureas) within last 4 weeks of starting treatment concurrent corticosteroids within 2 weeks prior to treatment radiotherapy within 2 weeks prior to treatment systemic antibiotics within 72 hours prior to treatment prior organ allograft antihistamine therapy within 5 days before or after administration of study vaccine chemotherapy during and for 4 weeks after administration of study vaccine adjuvant therapy during and for 4 weeks after administration of study vaccine other concurrent investigational agents

Ages Eligible for Study
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Minimum Age: 18 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: dendritic cell vaccine<br> | Biological: glioma-associated antigen peptide-pulsed autologous dendritic cell vaccine<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicity and maximum tolerated dose of autologous dendritic cells pulsed with synthetic glioma-associated antigen (GAA) peptides |  | 3 months | 
| Survival |  | 1 year | 
| Tumor progression |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adult anaplastic astrocytoma, adult glioblastoma, adult giant cell glioblastoma, adult gliosarcoma, adult anaplastic oligodendroglioma, recurrent adult brain tumor, adult mixed glioma