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