Safety and Efficacy Study in Recurrent or Progressive Grade III or IV IDH1 Mutated Glioma

Inclusion Criteria To be eligible to participate in the study, a patient must meet all of the following inclusion criteria: * Patient must have radiographically-confirmed progression of, or recurrent, primary or secondary Grade IV glioma, including infratentorial (brainstem, cerebellar) glioma (confirmed by biopsy) and subcortical glioma. * Patient must have radiographically-confirmed progression of, recurrent, primary or secondary Grade III astrocytoma. * All patients must be on a stable or decreasing dose of steroids for at least five days prior to the date of informed consent. * Patient must have failed previous radiation treatment or combined treatment with temozolomide and radiation. * If progression of disease occurs within 90 days of conformal radiation, the progression/recurrence must be outside of the radiation field or proven by biopsy/resection. * Patient must be ≥ 18 years of age. * Patient must have an ECOG performance status of 0-2 or KPS ≥ 60 (the latter for Phase 1 only). * Patient must have an expected survival of at least three months. * Patient must have a baseline MRI with gadolinium within 14 days of first administration of study drug. * Patient must be willing to provide blood samples for pharmacokinetic study. * If patient suffers from seizures, (s)he must be controlled on a stable dose of anti- epileptics for 14 days prior to the date of informed consent. * Patient must have adequate organ and marrow function as defined below: * Absolute neutrophil count ≥ 1,500/mcL * Platelets ≥ 100,000/mcL * Total bilirubin within normal institutional limits * AST (SGOT)/ALT (SPGT)≤ 2.5 × institutional upper limit of normal * Creatinine within normal institutional limits * Female patients of child-bearing potential and male patients must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for 30 days prior to the first administration of study drug, for the duration of study participation, and for 90 days following completion of therapy. Should a female patient become pregnant, or suspect she is pregnant, while participating in this study, she should inform her treating physician immediately. * A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: * Has not undergone a hysterectomy or bilateral oophorectomy; or * Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months). * A negative serum pregnancy test will be required of all female patients of child-bearing potential within seven days prior to initiating study drug. * A serum pregnancy test will be repeated immediately if pregnancy is suspected. * Patient must have the ability to understand, and the willingness to sign, a written informed consent. Phase 2a In addition to meeting Inclusion Criteria for the Phase I portion of the study, patients eligible for participation in the Phase 2a portion of the study must additionally meet the following criteria: • Patients must have a confirmed IDH1 mutation by reverse transcription polymerase chain reaction (rtPCR) or immunohistochemistry (unless continuing into the Phase 2a portion of the study from the Phase I portion of the study). Exclusion Criteria * If the patient meets any of the following criteria, the patient must not be enrolled: * The size of the tumor is \> 30mm (length x width), as assessed at the baseline (pre- study) MRI evaluation. * The tumor is multi-focal, as assessed at the baseline (pre-study) MRI evaluation. * Patient has completed chemo-radiation within the last 90 days prior to first administration of study drug, unless new contrast enhancement is outside of radiation field, or there is tissue proven recurrence or progression. * Patient has had surgery within seven days prior to the date of informed consent. * Patient has had any form of anti-cancer therapy or treatment within 28 days prior to first administration of study drug. * Patient has not recovered from adverse events due to chemotherapy, immunotherapy, or radiation therapy administered more than 28 days prior to first administration of study drug. * Patient has had prior treatment with bevacizumab, a chemotherapy wafer implant (Gliadel®), or any other FDA-approved anti-cancer therapy or treatment except temozolomide. * Patient has had more than one recurrence or progression of his/her tumors. * Patient has received any other investigational agents within 28 days prior to the first administration of study drug. * Patient has had prior treatment with perillyl alcohol, administered either intravenously or intranasally. * Patient has a history of allergic reactions attributed to perillyl alcohol. * Patient has 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. * Patient must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants. * Patient has a history of new diagnosis or treatment of cancer other than malignant glioma within five years prior to the date of informed consent, except for basal cell carcinoma or squamous cell carcinoma of the skin. * Leptomeningeal involvement of the patient's tumor.