Study researchers think that a drug called enasidenib may help people with clonal cytopenia of undetermined significance (CCUS) because the drug blocks the mutated IDH2 protein, which may improve blood cell counts. The purpose of this study is to find out whether enasidenib is a safe and effective treatment for CCUS.

Inclusion Criteria:

• Unexplained cytopenia for at least 6 months. Cytopenia is defined as the presence of ≥1 blood count indexes below the following thresholds:

  • Hgb <10 g/dL
  • ANC <1.8 × 109/L
  • Platelets <100 × 109/L

• IDH2 gene mutation (R140 or R172), performed locally, at a frequency ≥ 2%.

• At least 18 years of age.

• ECOG performance status 0-2

• Adequate organ function as defined below:

  • AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
  • Serum total bilirubin < 1.5 x IULN (un upper limit of bilirubin 5 mg/dL is acceptable if it can be attributed to Gilbert's syndrome or erythropoiesis)
  • Creatinine clearance > 50 mL/min by Cockcroft-Gault glomerular filtration rate estimation or serum creatinine ≤ 2 x IULN

• The effects of enasidenib on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 24 months after the last dose of enasidenib. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of the study, and for 4 months after the last dose of enasidenib.

• Ability to understand and willingness to sign an IRB approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.

Exclusion Criteria:

• Indication of hematologic disease by bone marrow biopsy within 6 months of study entry.

  • Evidence of disease progression from time of bone marrow biopsy to enrollment based on investigator review of symptoms and complete blood counts

• Active malignancy (defined as > 1 cm disease on most recent CT scan in the past 6 months).

• Currently receiving therapy for solid tumor malignancy or received within the last 6 months.

• Currently receiving any other investigational agents.

• Known dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally.

• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to enasidenib or other agents used in the study.

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.

• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 72 hours of study entry.

• Positive direct Coombs test.

Individual participant data that underlie the results reported in this article after deidentification (including text, tables, figures and appendices) will be available.

The data will be available immediately following publication with no end date.

The data will be available immediately following publication with no end date. Access will be provided to anyone and for any purpose.