• Humoral and cellular immune response [ Designated as safety issue: No ]
• Clinical efficacy of vaccination, in terms of progression-free survival [ Designated as safety issue: No ]

• Response to vaccination [ Designated as safety issue: No ]
• Toxicity [ Designated as safety issue: Yes ]

RATIONALE: Vaccines made from a peptide may help the body build an effective immune response to kill tumor cells. Colony-stimulating factors, such as GM-CSF, increase the number of white blood cells and platelets found in bone marrow or peripheral blood. Giving vaccine therapy after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This randomized phase II trial is studying how well vaccine therapy works in treating patients with newly diagnosed glioblastoma multiforme.

OBJECTIVES:

Primary

• To assess humoral and cellular immune responses to adjuvant PEP-3-KLH conjugate vaccine in patients with newly diagnosed glioblastoma multiforme (GBM).
• To assess the clinical efficacy of the PEP-3-KLH conjugate vaccine, in terms of progression-free survival, in patients with newly diagnosed GBM.

Secondary

• To determine whether patients with GBM, who are known to be at least mildly immunosuppressed, can respond to standard and proven vaccine strategies.
• To assess for any potential toxicity to the PEP-3-KLH conjugate vaccine in patients with newly diagnosed GBM.

OUTLINE: This is a 2-part, multicenter study. Patients are stratified according to participating center.

• Part 1: Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive PEP-3-KLH conjugate vaccine and sargramostim (GM-CSF) intradermally on days 1, 15, and 29 and then monthly in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients receive placebo vaccine intradermally on days 1, 15, and 29. Patients then receive PEP-3-KLH conjugate vaccine and GM-CSF monthly in the absence of disease progression or unacceptable toxicity.
• Part 2: Patients receive PEP-3-KLH conjugate vaccine and GM-CSF intradermally on days 1, 15, and 29 and then monthly in the absence of disease progression or unacceptable toxicity. Alternatively, patients receive PEP-3-KLH conjugate vaccine and GM-CSF intradermally on days 1, 8, and 15, followed 1 week later by radiotherapy 5 days a week and oral temozolomide once daily for up to 7 weeks. Patients with no evidence of disease progression after completion of radiotherapy then receive PEP-3-KLH conjugate vaccine and GM-CSF intradermally monthly in the absence of disease progression or unacceptable toxicity. Beginning approximately 4 weeks after the completion of radiotherapy or after the fourth vaccination, all patients receive oral temozolomide on days 1-5 or days 1-21. Treatment with temozolomide repeats every 28 days for at least 6 months.

Patients undergo delayed-type hypersensitivity (DTH) skin testing* at baseline, after the third vaccination, and then monthly thereafter. Patients also undergo leukapheresis to obtain sufficient peripheral blood lymphocytes for immunologic monitoring at baseline, after the third vaccination, and then, if applicable, at the time of positive DTH response, disease progression, or after the sixth course of post-radiotherapy temozolomide. Methods used for immunologic monitoring include ELISPOT assays, cytotoxicity assays, fluorescence activated cell sorting (FACS), and ELISA.

NOTE: *Patients with positive DTH skin testing, also undergo skin punch biopsies.

After completion of study therapy, patients are followed periodically.

• Biological: PEP-3-KLH conjugate vaccine
• Biological: sargramostim
• Other: placebo

• Experimental: Patients receive PEP-3-KLH conjugate vaccine and sargramostim (GM-CSF) intradermally on days 1, 15, and 29 and then monthly in the absence of disease progression or unacceptable toxicity.
• Active Comparator: Patients receive placebo vaccine intradermally on days 1, 15, and 29. Patients then receive PEP-3-KLH conjugate vaccine and GM-CSF monthly in the absence of disease progression or unacceptable toxicity.

DISEASE CHARACTERISTICS:

• Histologically confirmed newly diagnosed glioblastoma multiforme

• Has undergone prior gross total resection (GTR) followed by conformal radiotherapy* with or without concurrent chemotherapy

  • GTR is defined as ≥ 95% volumetric resection of the contrast-enhancing component on the preoperative MRI
  • Residual radiographic contrast enhancement on post-resection CT scan or MRI must be ≤ 1 cm in maximal diameter in any two perpendicular axial planes
  • No evidence of disease progression after completion of radiotherapy* NOTE: *Patients may enroll in part 2 of the study within 2 weeks after surgery; these patients will receive radiotherapy with concurrent chemotherapy during the study
• EGFRvIII-positive tumor by immunohistochemistry, polymerase chain reaction, or related molecular techniques
• No diffuse leptomeningeal disease

PATIENT CHARACTERISTICS:

• Karnofsky performance status 80-100%
• Curran group status I-IV
• ANC > 1,000/mm³
• Platelet count > 50,000/mm³
• PT/PTT < 1.5 times normal
• Negative hepatitis B surface antigen (HbsAg), antibody to hepatitis B surface antigen (anti-HBs), and antibody to hepatitis B core antigen (anti-HBc)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active infection requiring treatment
• No unexplained febrile illness (T_max > 101.5 F)
• No inflammatory bowel disease, lupus erythematosus, rheumatoid arthritis, or other autoimmune disease
• No known immunosuppressive disease
• No known HIV infection
• No unstable or severe concurrent medical condition, such as severe heart and lung disease or active hepatitis
• No demonstrated allergy to temozolomide or inability to tolerate temozolomide for reasons other than lymphopenia

PRIOR CONCURRENT THERAPY:

• No concurrent corticosteroids (except for nasal or inhaled steroids) at a dose above physiologic levels (> 2 mg of dexamethasone/day)