Brain and Central Nervous System Tumors
Conditions
Keywords
adult glioblastoma, adult anaplastic astrocytoma, adult brain tumor, adult giant cell glioblastoma, adult gliosarcoma, adult anaplastic oligodendroglioma
Brief summary
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
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.
Interventions
BIOLOGICALtherapeutic autologous dendritic cells
Sponsors
National Institutes of Health (NIH)
Jonsson Comprehensive Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose Limiting Toxicity | 4 weeks |
Secondary
| Measure | 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 |
Countries
United States
Outcome results
None listed