Vaccine Therapy in Treating Patients With Malignant Glioma

Study Overview
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Brief Summary
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RATIONALE: Vaccines made from a person's white blood cells mixed with tumor proteins may make the body build an 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 tumor lysate-pulsed dendritic cells in patients with malignant gliomas. Determine survival, tumor progression, and cellular immune response in patients treated with this regimen. OUTLINE: This is a dose-escalation study. 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 and pulsed with autologous tumor lysate. Patients receive autologous tumor lysate-pulsed DC intradermally on days 0, 14, and 28 in the absence of unacceptable toxicity. Cohorts of 6-12 patients receive escalating doses of autologous tumor lysate-pulsed DC until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Patients are followed every 2 months for 2 years. PROJECTED ACCRUAL: A total of 3-18 patients will be accrued for this study within 9-18 months.

Official Title
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Phase I Dose Escalation Study of Autologous Tumor Lysate-Pulsed Dendritic Cell Immunotherapy for Malignant Gliomas

Conditions
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Brain and Central Nervous System Tumors

Intervention / Treatment
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* Biological: therapeutic autologous dendritic cells


Participation Criteria
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Eligibility Criteria
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Eligibility Criteria: Histologically confirmed diagnosis of one of the following malignant gliomas: Anaplastic astrocytoma Glioblastoma multiforme Anaplastic oligodendroglioma Malignant mixed oligoastrocytoma WHO grade III or IV disease Newly diagnosed disease Bidimensionally measurable disease by contrast-enhancing MRI Surgically accessible tumor for which resection is indicated Previously treated with or plan to undergo treatment with conventional external beam radiotherapy Age 18 and over Performance status Karnofsky 60-100% Life expectancy at least 8 weeks Hemoglobin at least 10 g/dL Absolute granulocyte count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 SGOT and SGPT no greater than 2 times normal Alkaline phosphatase no greater than 2 times normal Bilirubin no greater than 1.5 mg/dL Hepatitis B negative Hepatitis C negative BUN no greater than 1.5 times normal Creatinine no greater than 1.5 times normal HIV negative Syphilis serology negative Afebrile Negative pregnancy test Fertile patients must use effective contraception At least 2 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered. At least 2 weeks since prior corticosteroids At least 2 weeks since prior radiotherapy and recovered More than 72 hours since prior systemic antibiotics 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 pregnant or nursing 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 concurrent chemotherapy during and for 2 weeks after administration of study vaccine concurrent corticosteroids prior organ allograft antihistamine therapy within 5 days before or after administration of study vaccine other concurrent investigational agents concurrent adjuvant therapy during and for 2 weeks after administration of study vaccine

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: autologous tumor lysate-pulsed DC<br> | Biological: therapeutic autologous dendritic cells<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Limiting Toxicity |  | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to tumor progression, overall survival and cellular immune responses in brain tumor patients injected with tumor lysate pulsed dendritic cells |  | 2 years | 

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