• 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 ]
  

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.