A Study of Enasidenib in People With Clonal Cytopenia of Undetermined Significance

Inclusion Criteria:

• Age ≥18 years at the time of signing the informed consent form.

• Willing and able to adhere to the study visit schedule and other protocolrequirements.

• 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 × 10^9/L

• Platelets <100 × 10^9/L

• Results of bone marrow biopsy within 1 month of study entry (screening bone marrowbiopsy) must not indicate hematologic disease.

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

• ECOG performance status of 0-2.

• Adequate organ function, defined as:

• Serum aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤3x upper limit of normal (ULN), unless the subject has Gilbert's syndrome.

• Serum total bilirubin <1.5x ULN. Higher levels are acceptable if these can beattributed to ineffective erythropoiesis. In these cases, approval from thestudy Principal Investigator is required.

• Creatinine clearance greater than 50 mL/min based on the Cockroft-Gaultglomerular filtration rate estimation.

• Patients being enrolled on study on the basis of anemia, will only be eligible iffolate, B12, serum iron, serum ferritin, total iron binding capacity, haptoglobinand peripheral smear within normal limits

• Women of childbearing potential may participate provided they have a negative serumpregnancy test at screening and a negative serum or urine pregnancy test within 72 hof starting treatment.

• Women of childbearing potential (WOCBP) and males with partners who are WOCBP mustagree to abstain from sexual intercourse or to use 1 highly effective form ofcontraception during the study and for at least 4 months following the last dose ofenasidenib. Males with partners who are WOCBP must agree to use a barrier method.

Exclusion Criteria:

• Active malignancy defined as >1-cm disease on most recent CT scan in the past 6months or recent history of cancer (i.e. within the past 5 years) with >50% chanceof cancer recurrence in the next 5 years.

• Current or prior history of hematologic malignancy.

• Therapy (including maintenance therapy) for solid-tumor malignancy within the last 6months.

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

• Active uncontrolled systemic fungal, bacterial, or viral infection (defined asongoing signs/symptoms related to the infection without improvement despiteappropriate antibiotics, antiviral therapy, and/or other treatment).

• Positive direct Coombs test

• Evidence of hypersplenism on physical exam

• Pregnant or lactating (women).