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

NCT06630221 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: CASE2924
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia

Keywords

MDS; CMML

Outcome Measures

Primary Outcomes (1)

• Response Rate as assessed by hematologic response

  Response rate will be assessed to determine whether treatment with EPAG can induce a hematologic response. The different types of hematologic improvement are Erythroid response (non-transfusion dependent, Erythroid response (transfusion dependent), Platelet response (pretreatment, \> 20 × 109/L), Platelet response (pretreatment, \< 20 × 109/L), Neutrophil response, and Progression or relapse after HI (after reaching maximum dose, and on maximum dose for 12 weeks).

  At end of treatment (approximately up to 12 weeks)

Secondary Outcomes (6)

• AML-free survival

  At end of treatment (approximately up to 12 weeks)

• Progression Free Survival

  At end of treatment (approximately up to 12 weeks)

• Change in TET2 mutation burden as measured by variant allele fraction.

  Baseline, end of cycle 3(28 days per cycle), end of treatment(approximately up to 12 weeks)

• Rates of robust response as measured by platelet count

  Approximately at 24 weeks post administration of intervention

• Rates of robust response as measured by hemoglobin

  Approximately at 24 weeks post administration of intervention

Study Arms (1)

Eltrombopag (EPAG)

EXPERIMENTAL

Enrolled participants will receive EPAG 50 mg daily, 2h prior to or after meals for 1 cycle

Drug: Eltrombopag (EPAG)

Interventions

Eltrombopag (EPAG) DRUG

50 mg, 28-day cycles, 3 initial cycles + 12 cycles on extension arm (maximum of 15 cycles)

Also known as: Promacta

Eltrombopag (EPAG)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

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

Sponsors & Collaborators

• Abhay Singh, MD MPH: lead

Study Sites (1)

Case Comprehensive Cancer Center, Cleveland Clinic Foundation Taussig Cancer Institute

Cleveland, Ohio, 44195, United States

RECRUITING

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic

Interventions

eltrombopag

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Abhay Singh, MD, MPH

  Case Comprehensive Cancer Center, Cleveland Clinic Taussig Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Abhay Singh, MD, MPH

CONTACT

1-866-223-8100; TaussigResearch@ccf.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 4, 2024
• First Posted: October 8, 2024
• Study Start: June 17, 2025
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2030
• Last Updated: July 3, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data included in the peer reviewed publication will be publicly available starting 6 months after publication and will be available indefinitely. No raw data will be shared.
• Access Criteria: A peer-reviewed publication will be made available according to the publishing journal's specifications. CCF personnel will not share study data apart from that which has been published publicly.

Locations

US (1)