Eltrombopag as a Novel Therapeutic Approach for Low-risk MDS and CMML With TET2 Mutations

Paused · Phase 2

Conditions studied: Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia

In brief

The purpose of this study is to evaluate if a study drug called eltrombopag can improve the blood cell counts in patients with low-risk Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML) with mutations in TET2 gene, observe changes in the TET2 gene over time, and evaluate the effectiveness of the treatment. TET2 gene is one of the most frequently mutated genes (altered parts of the DNA) in MDS and CMML. Eltrombopag is a Food and Drug Administration (FDA) approved drug for the treatment of severe aplastic anemia and low levels of platelets in patients with persistent or chronic immune thrombocytopenia (ITP) and chronic hepatitis C. Eltrombopag is considered investigational (experimental) in this study because the FDA has not approved its use in the treatment of low-risk MDS or CMML. Eltrombopag is a drug that helps stimulate the body's process of making more platelets (small components of blood that help with clotting) by interacting with specific parts of cells. This interaction starts a series of signals that encourage the growth and development of the cells that produce platelets. It was found that this drug could stop the growth of TET2 mutated cells.

Key facts

Study ID: NCT06630221
Run by: Abhay Singh, MD MPH
People needed: 25
Starts: 2025-06-17
Expected to finish: 2030-01-01
Last updated by the study team: 2026-06-05

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

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 (IPSS-R < 3.5) and < 5% myeloblasts or CMML 0 (CMML-0, for cases with < 2% blasts in PB and < 5% blasts in bone marrow (BM)z,[14] with any one of the notable cytopenias as defined below:
Hgb < 10 g/dL prior to enrollment
ANC < 1.5×10\^9/L
Platelets < 100×10\^9/L
Must be relapsed, refractory/resistant, intolerant, or have inadequate response to therapies with known clinical benefits for MDS, such as EPOs, luspatercept, and 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%.
ECOG performance status of 0-2.
Adequate organ function, defined as:
Serum total bilirubin < 2x 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 PI is required.
Creatinine clearance greater than 30 mL/min based on the Cockroft-Gault glomerular filtration rate estimation.
Participants 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 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 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.

You may not qualify if…

High- and Very High-risk MDS (per IPSS-R)
CMML 1-2
Prior HMA exposure
Platelet count > 200×10\^9/uL or leukocytosis of at least 25×10⁹/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-2.
Elevated LFTs (aminotransferases and bilirubin) > 2x 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)

Where it is running

Case Comprehensive Cancer Center, Cleveland Clinic Foundation Taussig Cancer Institute — Cleveland, Ohio, United States

Full record on ClinicalTrials.gov

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