Eltrombopag for the Treatment of Relapsed or Refractory Very Low, Low, or Intermediate Risk Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia-0 with TET2 Mutations

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 protocol requirements
• Established diagnosis of very low-, low-, or intermediate-risk MDS (Revised International Prognostic Scoring System [IPSS-R] ≤ 3.5) and ≤ 5% myeloblasts or CMML 0 (CMML-0, for cases with < 2% blasts in peripheral blood [PB] and < 5% blasts in bone marrow [BM]), with any one of the notable cytopenias as defined below: * Hemoglobin (Hgb) < 10 g/dL prior to enrollment * Absolute neutrophil count (ANC) < 1.5 x 10^9/L * Platelets < 100 x 10^9/L
• Must be relapsed, refractory/resistant, intolerant, or have inadequate response to therapies with known clinical benefits for MDS, such as epoetin alphas (EPO)s, luspatercept, and hypomethylating agents (HMAs) (i.e., azacytidine or decitabine). Patients with del (5q) must have failed prior lenalidomide therapy
• TET2 mutation performed at a frequency of at least > 5%
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Serum total bilirubin < 2 x upper limit of normal (ULN), unless the subject has Gilbert’s syndrome. Higher levels are acceptable if these can be attributed to ineffective erythropoiesis. In these cases, approval from the study principal investigator (PI) is required
• Creatinine clearance greater than 30 mL/min based on the Cockroft-Gault glomerular filtration rate estimation
• Patients being enrolled on study on the basis of anemia, will only be eligible if folate, B12, serum iron, serum ferritin, total iron binding capacity, haptoglobin and peripheral smear within normal limits
• Hepatitis panel negative for hepatitis (Hep) B and Hep C infection
• Negative for HIV infection
• Women of childbearing potential (WOCBP) may participate provided they have a negative serum pregnancy test at screening and a negative serum or urine pregnancy test within 72 hours (h) of starting treatment
• WOCBP and males with partners who are WOCBP must agree to abstain from sexual intercourse or use effective contraception (methods that result in < 1% pregnancy rates) during eltrombopag therapy and for at least 7 days after the last eltrombopag dose. Males with partners who are WOCBP must agree to use a barrier method

Exclusion Criteria

• High- and very high-risk MDS (per IPSS-R)
• CMML 1-2
• Prior HMA exposure
• Platelet count > 200 x 10^9/uL or leukocytosis of at least 25 x 10^9/L
• Marrow fibrosis (any grade)
• Results of bone marrow biopsy within 1 month of study entry (screening bone marrow biopsy) indicating high-risk MDS or CMML 1-2
• Elevated liver function tests (LFTs) (aminotransferases and bilirubin) > 2 x ULN
• Pre-existing cardiovascular disease (e.g., known coronary artery disease with percutaneous intervention or stroke within the last year) or arrhythmia (e.g., atrial fibrillation) associated with an increased risk of thromboembolic events, unless deemed acceptable by the enrolling treating physician
• History of arterial or venous thromboembolism, and on anticoagulation
• Severe hepatic impairment (Child-Pugh class C)
• Recent history of cancer (i.e., within the past 5 years) with > 50% chance of cancer recurrence in the next 5 years
• Current or prior history of hematologic malignancy
• Known dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally
• Active uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment.)
• Positive direct Coombs test
• Evidence of hypersplenism on physical exam
• Pregnant or lactating (women)
• Unable or unwilling to discontinue prior anticancer therapy. The use of intercurrent anticancer therapy (standard care or investigational) is not permitted. Any use of prior anticancer therapy is to be discontinued at least 14 days prior to cycle 1 day 1 (or longer depending on drug elimination properties). Note: the use of steroids for short terms intervals (≤ 14 days) or reasons not related to cancer therapy (e.g., topical, ocular, pulmonary, etc. purposes) is NOT exclusionary