SurVaxM Vaccine Therapy and Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma

Inclusion Criteria:

* Have a Karnofsky performance status \>= 70 (i.e. the patient must be able to care for himself/herself with occasional help from others)
* Documented survivin-positive tumor status
* Pathologically confirmed diagnosis of glioblastoma multiforme (GBM); or World Health Organization (WHO) grade IV \[gliosarcoma\]
* Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L
* Platelets \>= 100 x 10\^9/L
* Hemoglobin (Hgb) \> 9.0 g/dL
* Serum total bilirubin: =\< 1.5 x upper limit of normal (ULN)
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 4.0 x ULN
* Patients on full-dose anticoagulants (e.g., warfarin or low molecular weight \[LMW\] heparin) must meet the following criteria:

  * No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
* Creatinine =\< 1.8 mg/dl
* Human leukocyte antigen (HLA)-A\*02, HLA-A\*03, HLA-A\*11 or HLA-A\*24 positive patients
* No evidence of progressive disease from the postoperative period to the post-chemoradiation period, based on changes in the neurologic exam, steroid use, or evident radiographic progression, according to RANO criteria; Patients with increased or new gadolinium enhancement may continue on protocol if in the investigator's judgment that enhancement is likely due to pseuodoprogresion. The use of correlative imaging studies (including PWI) or diffusion weighted imaging (DWI) and repeat imaging after an interval of 2-4 weeks is strongly encouraged to help distinguish between pseudoprogression and true progression.
* Magnetic resonance imaging (MRI) (ideally completed within 96 hours after surgery) documenting gross total resection consisting of no gadolinium enhancement; or subtotal resection consisting of linear enhancement with (or without) nodular gadolinium enhancement measuring no greater than 1 cm x 1 cm x 1 cm total volume or 100 mm\^2 in cross sectional area
* Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry, and have a negative pregnancy test prior to starting study treatment; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
* Dexamethasone dose less than or equal to 4 mg daily at time of study enrollment
* Patients must have completed initial radiation therapy (RT) and temozolomide (TMZ) for the treatment of their glioblastoma (i.e., completed 6-week course of RT and, completed \>= 75% of 6-week course of induction TMZ chemotherapy)
* Participant must understand the investigational nature of this study and sign an independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

Exclusion Criteria:

* The patient must not have received any immunotherapy for their brain tumor
* Patients with serious concurrent infection or medical illness, which in the treating physician's opinion would jeopardize the ability of the patient to receive the treatment outlined in this protocol with reasonable safety
* Patients who are pregnant or breast-feeding
* Patients receiving concurrent therapy for their tumor (i.e. chemotherapeutics or investigational agents) other than temozolomide
* Patients with a concurrent or prior malignancy are ineligible unless they are patients with curatively treated carcinoma-in-situ or basal cell carcinoma of the skin; patients who have been free of disease (any prior malignancy) for at least 3 years are eligible for this study
* Patients who have had repeat craniotomy for tumor therapy after receiving RT and TMZ treatment
* Patients who received other chemotherapeutics or investigational agents in addition to their radiation therapy and concomitant temozolomide treatment
* Patients who have received Gliadel wafers or alternating electrical field therapy (ETTF) are not eligible for this study
* Known history of an autoimmune disorder
* Known human immunodeficiency virus (HIV) positivity or acquired immunodeficiency syndrome (AIDS) related illness or other serious medical illness
* Patients who have contraindication to MRI
* Unwilling or unable to follow protocol requirements
* Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug
* Received an investigational agent within 30 days prior to registration