Vaccine Therapy in Treating Patients With Recurrent Glioblastoma

Inclusion Criteria:

* First or second recurrence of previously histologically confirmed glioblastoma (grade 4 astrocytoma)

  * NOTE: gliosarcomas and other grade 4 astrocytoma variants (e.g., giant cell) may be included, primitive neuroectodermal tumor (PNET) variants are excluded; grade 4 oligodendrogliomas or oligoastrocytomas are specifically excluded
* Prior craniotomy and gross total or sub-total resection of tumor at this recurrence NOTE: biopsy of this recurrence alone without attempt at resection does not meet this inclusion criteria (i.e. craniotomy and resection is still required).
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
* Absolute neutrophil count (ANC) \>= 1500/uL
* Monocytes \>= 300/uL
* Platelets (PLT) \>= 100,000/uL
* Hemoglobin (HgB) \>= 9.0 g/dL
* Total bilirubin =\< 1.5 x upper limit of normal (ULN)
* Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) =\< 3 x ULN
* Creatinine =\< 1.5 x ULN
* Negative pregnancy test done =\< 7 days prior to registration, for persons of childbearing potential only
* Ability to understand and willingness to sign written informed consent
* Willing to return to Mayo Clinic in Rochester, Minnesota for follow-up
* Willing to provide tissue and blood samples for mandatory correlative research purposes
* Fixed or decreasing dose of corticosteroids (or no corticosteroids) \>= 7 days prior to registration

Exclusion Criteria:

* Prior treatment

  * Current or prior treatment for this cancer with immunotherapy and/or any other investigational agents
  * Surgery =\< 2 weeks prior to registration
  * Radiotherapy =\< 12 weeks prior to registration
  * Treatment with bevacizumab or any cytotoxic chemotherapy =\< 8 weeks prior to registration
* Any of the following

  * Pregnant persons
  * Nursing persons
  * Persons of childbearing potential who are unwilling to employ adequate contraception
* Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
* Immunocompromised patients (other than that related to the use of corticosteroids) including patients known to be human immunodeficiency virus (HIV), human T-cell lymphotropic virus (HTLV), hepatitis B (HepB), or hepatitis C (HepC) positive
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* History of other malignancy other than glioma

  * EXCEPTIONS: non-melanotic skin cancer, carcinoma-in-situ of the cervix, or systemic cancer that has been in documented remission for \> 10 years
  * NOTE: if there is a history or prior malignancy, they must not be receiving other specific treatment for their cancer
* History of myocardial infarction =\< 180 days (6 months), or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
* Active infection =\< 5 days prior to registration or fever \>/= 38 degrees Celsius (C) within 5 days prior to registration
* History of tuberculosis or positive purified protein derivative (PPD) test
* Inability or unwillingness to have magnetic resonance imaging (MRI) scans performed (e.g. cardiac pacemaker-dependent)