Vaccine Therapy in Treating Patients With Malignant Glioma
Vaccine Therapy in Treating Patients With Malignant Glioma
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.
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.
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