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

Launched by ABHAY SINGH, MD MPH · Oct 4, 2024

Keywords

ClinConnect Summary

This clinical trial is investigating a drug called eltrombopag as a possible new treatment for patients with low-risk Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML) who have a specific genetic mutation known as TET2. The goal is to see if eltrombopag can help improve blood cell counts in these patients, monitor changes in the TET2 gene over time, and assess how effective the treatment is. Eltrombopag is already approved for other blood-related conditions but is being studied here for its potential benefits in MDS and CMML.

To be eligible for this trial, participants must be at least 18 years old and have a confirmed diagnosis of low-risk MDS or CMML with certain blood count issues. They should have not responded well to previous treatments or have experienced side effects from them. Participants will be closely monitored during the trial, and it is important for them to follow the study schedule and guidelines. Additionally, women who can become pregnant must take precautions to avoid pregnancy during the study. This trial is not open for recruitment yet, but it aims to provide valuable insights into treating these blood conditions.

Gender

ALL

Eligibility criteria

• 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 (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:
• • 1. Hgb \< 10 g/dL prior to enrollment
• • 2. ANC \< 1.5×10\^9/L
• • 3. 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:
• • 1. 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.
• • 2. Creatinine clearance greater than 30 mL/min based on the Cockroft-Gault glomerular filtration rate estimation.
• • 3. 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
• • 4. Hepatitis panel negative for Hep B and Hep C infection
• • 5. 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.
• Exclusion Criteria:
• • 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)