Potential subjects with progressive Grade II primary brain tumor that have IDH1 positive testing from the primary tumor (initial diagnosis) will be offered this treatment study in order to test the safety of the PEPIDH1M vaccine in combination with standard chemotherapy (temozolomide).

After informed consent has been signed, subjects will undergo standard of care vaccination with 0.5 mL of Td (tetanus and diphtheria toxoids adsorbed) intramuscularly into the deltoid muscle to ensure adequate immunity to the tetanus antigen.

Eligible subjects will undergo a 1-2 hour leukapheresis (to pull off white blood cells) for immune monitoring. Within 48 hours of leukapheresis, subjects will receive vaccine site pre-conditioning as a single dose of Td toxoid (in a total volume of 0.4 mLs salt water/saline) given in the intradermal space (just under the surface of the skin) to the right groin area. The pre-conditioning will be administered one day prior to receiving PEPIDH1M vaccine. The peptide vaccine is administered in the upper thigh area approximately 4 inches below the groin in the intradermal space as vaccine # 1. Subsequent vaccines will be given on day 15 ±3 days (vaccine #2) and day 29 ±3 days (vaccine #3). Each injection of the peptide vaccine will be given half on the right groin and half on the left groin. The first 3 peptide vaccine injections will occur without temozolomide (standard of care chemotherapy).

Seven to twelve days after the 3rd vaccine, subjects will have standard of care surgery to remove the tumor. Tumor samples will be evaluated for the IDH1 markers and analyzed for other cells that may have entered the tumor.

Based on the the tissue obtained at surgery, subjects with stable histologic grade at recurrence will then be treated with vaccine and temozolomide. During monthly cycles of temozolomide, subjects will receive the vaccine on day 22 (+ 2 days) for a maximum of 15 total vaccines (which includes the first 3 bi-weekly vaccines). Patients that have transitioned to a higher grade brain tumor at the time of surgery will receive temozolomide and radiation therapy per standard of care and monthly vaccines (vaccines #4-6). After completion of radiation therapy, subjects in this treatment group will receive vaccines monthly on day 22 (+2 days) with post-RT cycles of TMZ to a maximum of 15 vaccines.

All Adverse Events will be collected from time of consent until off study. The treatment phase of the study will end 1 month after the last vaccine. Patients will be followed only for overall survival, progression-free survival, and subsequent therapies thereafter.

Subjects will have blood collected for immune monitoring and biomarker testing during the following times: prior to initiating vaccine therapy (at the leukapheresis visit), prior to surgery to remove the tumor, at the clinic visit prior to starting first cycle of temozolomide after surgery (or radiation therapy and temozolomide for those who transition to higher grade), at vaccine #6, and at end of vaccine treatment (1 month after vaccine #15 or time the subject comes off study, whichever comes first).

Subjects will be imaged with contrast-enhanced magnetic resonance imaging (MRI) according to standard of care every 10 weeks (+/- 4 weeks) while on temozolomide and afterward, per the treating neuro-oncologist's recommendation. Revised Assessment in Neuro-Oncology (RANO) criteria will be used for assessment of pseudoprogression and tumor progression. Subjects demonstrating definitive progression will be removed from study.

As part of standard care for these subjects, upon tumor progression, participants may undergo biopsy or resection. As this is not a research procedure, consent will be obtained separately. Subjects that have this procedure done within the Duke University Health System will be asked to have a portion of the tumor sample, if possible, to assess immunologic cell infiltration, antigen expression, and biomarkers for immunologic response.

Please note, data collection will continue to occur outside of the defined primary and secondary outcomes for exploratory objectives.

The specific exploratory objective involves describing the progression free survival (PFS) and overall survival (OS). The endpoint is the proportion of patients alive without disease progression 6 months after initial vaccine treatment, and both the median PFS, and the median OS.

The objective will be reviewed at 3 years after the last subject came off study.

Inclusion Criteria:

1. Age ≥ 18 years.

2. IDH1R132H expression in primary tumor

3. Radiographic and/or clinical progressive and resectable Grade II glioma.

4. Signed informed consent.

5. For females of child-bearing potential, negative serum pregnancy test at screening (within 48 hours prior to leukapheresis)

6. Women of childbearing potential and male participants must agree to practice adequate contraception.

7. Karnofsky Performance Status (KPS) of ≥ 70.

8. Complete Blood Count (CBC)/differential with adequate bone marrow function as defined below within 2 weeks of enrollment:

   • Absolute neutrophil count, ≥ 1500 cells/mm3.
   • Platelet count, ≥ 100,000 cells/mm3.
   • Hemoglobin ≥ 10 g/dl. (Note: the use of transfusion or other intervention to achieve Hgb ≥ 10 g/dl is acceptable.)

9. Adequate renal function as defined below within 2 weeks of enrollment:

   • Blood Urea Nitrogen (BUN) ≤ 25 mg/dl.
   • Creatinine ≤ 1.7 mg/dl.

10. Adequate hepatic function as defined below within 2 weeks of enrollment:

    • Bilirubin ≤ 2.0 mg/dl.
    • Alanine Aminotransferase (ALT) ≤ 3 x normal range.
    • Aspartate Aminotransferase (AST) ≤ 3 x normal range

Exclusion Criteria:

1. Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease free for ≥ 3 years. (For example, carcinoma in situ of the breast, oral cavity, and cervix are all permissible.)

2. Metastases detected below the tentorium or beyond the cranial vault.

3. Severe, active co-morbidity, defined as follows:

   • Unstable angina and/or congestive heart failure requiring hospitalization.
   • Myocardial infarction within the last 6 months.
   • Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because treatments involved in this protocol may be significantly immunosuppressive.
   • Major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy.

4. Pregnant or lactating women, due to possible adverse effects on the developing fetus or infant due to study drug.

5. Prior allergic reaction to temozolomide.

6. Patients treated on any other therapeutic clinical protocols within 30 days prior to study entry or during participation in the study.

7. Patients with known hypersensitivity to GM-CSF, yeast-derived products, or any component of Leukine®.

8. Allergy or hypersensitivity to tetanus vaccine or any component of the tetanus vaccine.

9. Unable to undergo MRI imaging.

Date of consent through 2 months after the last vaccination