Nivolumab in Patients With IDH-Mutant Gliomas With and Without Hypermutator Phenotype

* INCLUSION CRITERIA:
* Patients must have recurrent diffuse glioma (histologically confirmed by National Institutes of Health (NIH) Laboratory of Pathology) with isocitrate dehydrogenase 1 (IDH1) or isocitrate dehydrogenase 2 (IDH2) mutation (confirmed by deoxyribonucleic acid (DNA) sequencing, Foundation One is preferable for confirmation of mutation, but not necessary).
* Patients must have tumor specific mutation burden (number of somatic mutations per exome) tested at NIH: Must have either result of tumor mutation burden from the most recent surgical tumor sample or must provide adequate genomic materials of the sample for tumor testing. The tumor tissue (e.g., block or 15 unstained slides) must be available for molecular and immune profiling. Fresh or frozen tumor sample will be used if available, but not mandatory.
* Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of nivolumab in patients \<18 years of age, children are excluded from this study but will be eligible for future pediatric trials.
* Patient must be able to tolerate a magnetic resonance imaging (MRI) study with intravenous gadolinium contrast.
* Karnofsky greater than or equal to 60%
* Patients must have adequate organ and marrow function as defined below:

  * Absolute neutrophil count greater than or equal to 1,500/mcL
  * Platelet Count greater than or equal to 100,000/MCL
  * Hemoglobin greater than 9.0 g/dL (may be transfused to achieve this level)
  * Blood Urea Nitrogen (BUN) less than or equal to 30 mg/dL and
  * Serum creatinine less than or equal to 1.7 mg/dL
  * Total bilirubin (except patients with Gilbert's Syndrome, who are eligible for the study but exempt from the total bilirubin eligibility criterion) less than or equal to 2.0 mg/dL
  * Alanine aminotransferase (ALT) and aspartate aminotransaminase (AST) less than or equal to 2.5x institutional upper limit of normal.
* The effects of nivolumab on the developing human fetus are unknown. For this reason, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and up to 5 months (women). Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately.
* The patient must be able to understand and be willing to sign a written informed consent document.

EXCLUSION CRITERIA:

* Patients who are receiving any other investigational agents.
* Patients who have a history of receiving immune therapy.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab.
* History of severe hypersensitivity reaction to any monoclonal antibody.
* Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years prior to initiation of study therapy.
* Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids. These include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome or Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), myasthenia gravis; systemic autoimmune disease such as Systemic Lupus Erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome. Such diseases should be excluded because of the risk of recurrence or exacerbation of disease.

  --Of note, patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible. Patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible.
* The patient must not be currently on a corticosteroid dose greater than dexamethasone 1 mg per day or its equivalent.
* 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 (within timeframes identified in the bullets below) that would limit compliance with study requirements.
* Known human immunodeficiency virus (HIV)-positive or acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS is based on the lack of information regarding the safety of nivolumab in patients with active HIV infection
* Pregnant women are excluded from this study because nivolumab's potential for teratogenic or abortifacient effects is unknown. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with nivolumab, breastfeeding should be discontinued if the mother is treated with nivolumab.