Study of Acetazolamide With Temozolomide in Adults With Newly Diagnosed or Recurrent Malignant Glioma

Inclusion Criteria: * Histologically proven, newly diagnosed IDH wildtype glioblastoma (GBM) that has a methylated MGMT promoter as assessed by the standardized institutional analysis. * Patients are eligible if they had a prior low grade astrocytoma and there is subsequent histological evidence of a diagnosis of grade III or IV tumor. * Patients must be receiving TMZ as part of their standard adjuvant treatment regimen following treatment with TMZ and Radiation. * Patients must have a Karnofsky performance ≥ 60%. * Normal organ function as follows: * Absolute Neutrophil Count (ANC) ≥ 1.0 x 10\^9/ L * Platelets ≥ 100 x 10\^9 / L * Hemoglobin ≥ 8.0 g / dL * Age 18 years or older. * Kidney function (creatinine level within normal institutional limit, or creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine level above institutional normal). * Liver function (AST/ALT \<2.5 X institutional upper limit of normal (ULN), Total bilirubin ≤ 1.5 times ULN, INR within 1.5 times ULN (or if receiving anticoagulant therapy an INR of ≤ 3.0 is allowed with concomitant increase in PT or an aPTT ≤ 2.5 × control). * Women able to become pregnant must have a negative pregnancy test within 30 days of registration. * Patients must have the ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: * Prior invasive malignancy that is not low-grade glioma (except non-melanomatous skin cancer or carcinoma in situ of the cervix) unless the patient has been disease free and off therapy for that disease for a minimum of 3 years. * Active systemic infection requiring treatment, including any HIV infection or toxoplasmosis. * Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration. * Systemic corticosteroid therapy, \>8 mg of dexamethasone daily (or equivalent) at study enrollment. * Pregnant women are excluded from this study, where pregnancy is confirmed by a positive serum beta-hCG laboratory test. Breast-feeding should be discontinued. * Hypersensitivity to acetazolamide or sulfonamides.