Inclusion Criteria:
1. Age ≥ 18 years
2. IDH1R132H expression in primary tumor
3. Clinical and/or radiographic, progressive Grade 2-3 glioma with greater than 2 cm of non-enhancing disease in one plane.
4. 1st recurrence only
5. Signed informed consent
6. For females of child-bearing potential, negative serum pregnancy test at screening
7. Women of childbearing potential and male participants must agree to practice contraception
8. Karnofsky Performance Status (KPS) of ≥ 70
9. Expected survival of ≥ 12 months
10. Recovered from any clinically relevant toxicities associated with any prior surgery for the treatment of glioma unless stabilized under medical management
11. Complete Blood Count (CBC)/differential with adequate bone marrow function as defined below within 2 weeks of enrollment:
1. Absolute neutrophil count (ANC) ≥ 1000 cells/mm3
2. Platelet count ≥ 100,000 cells/mm3
3. Hemoglobin (Hgb) ≥ 10 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 10 g/dl is acceptable.)
12. Adequate renal function as defined below within 2 weeks of enrollment:
1. Blood urea nitrogen (BUN) ≤ 25 mg/dl
2. Creatinine ≤ 1.7 mg/dl
13. Adequate hepatic function as defined below within 2 weeks of enrollment:
1. Bilirubin ≤ 2.0 mg/dl
2. Alanine transaminase (ALT) ≤ 3 x normal range
3. 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 (e.g., 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. More than 1 cm X 1 cm of enhancing disease on gadolinium contrasted MRI imaging
4. Severe, active co-morbidity, defined as follows:
1. Unstable angina and/or congestive heart failure requiring hospitalization
2. Myocardial infarction within the last 6 months.
3. Known Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition (Note: human immunodeficiency virus \[HIV\] testing is not required for entry into this protocol. The need to exclude patients with Acquired Immunodeficiency Syndrome (AIDS) from this protocol is necessary because treatments involved in this protocol may be significantly immunosuppressive.)
4. Major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy.
5. Pregnant or lactating women, due to possible adverse effects on the developing fetus or infant due to study drug
6. Patients with a heart-rate corrected QT interval using Fridericia's formula (QTcF) ≥ 450 msec or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome)
7. Patients with known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Subjects with a sustained viral response to HCV treatment or immunity to prior HBV infection will be permitted (Note: Patients with chronic HBV that is adequately suppressed by institutional practice will be permitted.)
8. Patients with active gastrointestinal disease, chronic diarrhea, previous gastric resection or lap band dysphagia, short-gut syndrome, gastroparesis, or other condition that limits the ingestion or gastrointestinal absorption of drugs administered orally (Note: Gastroesophageal reflux disease under medical treatment is allowed.)
9. Patient taking any medications that are CYP3A or CYP2C9 substrates with a narrow therapeutic index (Note: Patients should be transferred to other medications before receiving the first dose of study drug.)
10. Patients treated on any other therapeutic clinical protocols within 30 days prior to study entry or during participation in the study
11. Patients with known hypersensitivity to GM-CSF, yeast-derived products, or any component of Leukine®
12. Allergy or hypersensitivity to tetanus vaccine or any component of the tetanus vaccine.
13. Known hypersensitivity to any component of vorasidenib
14. Prior therapy with mIDH1 targeted therapeutics
15. Unable to undergo MRI imaging
