Myelodysplastic SyndromesPhase 2NCT06630221
Eltrombopag as a Novel Therapeutic Approach for Low-risk MDS and CMML With TET2 Mutations
A Phase 2 study testing Eltrombopag (EPAG) in people with Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia, run by Abhay Singh, MD MPH at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia
- What is being tested?
- Eltrombopag (EPAG)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Jun 2025to 1 Jan 2030
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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.
Show all 17Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
Case Comprehensive Cancer Center, Cleveland Clinic Foundation Taussig Cancer Institute
Cleveland, Ohio, 44195
About this study
Official title: A Phase II Study of Eltrombopag as a Novel Therapeutic Approach for Patients With Low-risk Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML) With TET2 Mutations
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.
Read the detailed description
Epigenetic changes such as alterations in DNA methylation and histone modification play an important role in the pathophysiology of myelodysplastic syndromes (MDS). With the development of next-generation sequencing (NGS) platforms, it has become possible to identify genomic aberrations involved in the MDS epigenetics. Additionally, with the advances in therapeutic methods in MDS, several novel genomic aberrations have been reported to predict the effectiveness of specific treatment. It is becoming clear that genomic aberrations may offer more precise cancer phenotypes and help predict precise therapies for MDS patients (e.g. IDH1 and IDH2 inhibitors). TET2 gene is a member of the DNA methylation machinery and one of the most frequently mutated genes in MDS and chronic myelomonocytic leukemia (CMML; a disease entity similar to MDS with similar bone marrow dysplasia and accompanying cytopenias). TET DNA dioxygenases hydroxylate 5-methylcytosine (5mC) to 5-hydroxy-mC (5hmC), a process that leads to passive demethylation and thereby initiation of differentiation programs of hematopoietic stem cells (HSCs). TET2 mutations (TET2MT) often act as founder lesions for clonal hematopoiesis of indeterminate potential (CHIP). Our group has demonstrated that mutational exclusivity of TET2 and isocitrate dehydrogenases 1 and 2 (IDH1/2) result from production of a neomorphic natural TET2 inhibitor α-hydroxyglutarate (2HG). 2HG is selectively and synthetically lethal to TET2-deficient HSCs reliant for their survival on minimal residual dioxygenase activity supplied by less abundant TET1 and TET3. This observation inspired the idea of generating TET inhibitors as drugs selective for TET2 mutant (TET2MT) leukemia cells. Based on the structure of 2HG, investigator generated a more potent TETi76, and showed that this drug is indeed synthetically lethal to TET2MT and TET2 proficient cells. In search for alternative agents with suitable activity, investigator next performed a high throughput drug screen using an in vitro DNA dioxygenase assay. Among several hits, eltrombopag (EPAG) was unique, as it is already used in clinical practice as a thrombopoietin receptor (TPOR) agonist. Investigator showed that this agent inhibited growth of TET2MT cells in murine TET2MT models independent of its TPOR activity, and have determined its binding site and mode of action on TET dioxygenases.1 Since EPAG is an FDA approved drug with known toxicities and good tolerability, repurposing this agent as a TET inhibitor would greatly shorten the development time and thus rapidly provide a selective and well-tolerated drug for the therapy of patients with TET2MT MDS. Investigators have obtained granular molecular and response data from historical trials of EPAG/5Azacytidine in unselected MDS and aplastic anemia (AA) and were able to retrospectively assert that indeed those with TET2MT disease responded to EPAG therapy, resulting in decreased TET2MT clonal burden.
- Being tested
- Eltrombopag (EPAG)
- Keywords
- MDS, CMML
- Medical subject headings
- Myelodysplastic Syndromes, Leukemia, Myelomonocytic, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Eltrombopag (EPAG)Drug
Also called Promacta
50 mg, 28-day cycles, 3 initial cycles + 12 cycles on extension arm (maximum of 15 cycles)
| Study group | Role | What they receive |
|---|---|---|
| Eltrombopag (EPAG) | Experimental | Enrolled participants will receive EPAG 50 mg daily, 2h prior to or after meals for 1 cycle Receives: Drug: Eltrombopag (EPAG) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: At end of treatment (approximately up to 12 weeks)
Secondary outcomes (6)
AML-free survival
AML-free survival will be calculated using the Kaplan-Meier method
Measured: At end of treatment (approximately up to 12 weeks)
Progression Free Survival
Progression free survival will be calculated using the Kaplan-Meier method
Measured: At end of treatment (approximately up to 12 weeks)
Change in TET2 mutation burden as measured by variant allele fraction.
Change in mutant TET2 variant allele fraction
Measured: 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
Robust response will be summarized with a frequency and 95% confidence interval.
Measured: Approximately at 24 weeks post administration of intervention
Rates of robust response as measured by hemoglobin
Robust response will be summarized with a frequency and 95% confidence interval.
Measured: Approximately at 24 weeks post administration of intervention
Rates of robust response as measured by ANC
Robust response will be summarized with a frequency and 95% confidence interval.
Measured: Approximately at 24 weeks post administration of intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2024
- Study start17 Jun 2025
- Primary completion1 Jan 2028 (estimated)
- Study completion1 Jan 2030 (estimated)
Why it stopped: Funding unavailable
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myelodysplastic SyndromesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Abhay Singh, MD MPH
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Abhay Singh, MD MPH, Case Comprehensive Cancer Center
- Investigators
- Abhay Singh, MD, MPH, Principal investigator, Case Comprehensive Cancer Center, Cleveland Clinic Taussig Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06630221
- Sponsor's protocol ID
- CASE2924
- Status last verified
- Oct 2026
- First submitted
- 4 Oct 2024
- Last updated
- 9 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All IPD that underlie results in publication will be shared as a combined summary. Any individual outcomes published per subject will be de- identified utilizing the subject ID (e.g., dosing, demographics, adverse events, etc.)
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Eltrombopag as a Novel Therapeutic Approach for Patients With Low-risk Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML) With TET2 Mutations
- ClinicalTrials.gov ID
- NCT06630221
- Acronym / sponsor ID
- CASE2924
- Keywords
- MDS, CMML
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: Funding unavailable
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- Abhay Singh, MD MPHUniversity, hospital or other
- Study start
- 17 Jun 2025 (actual)
- Primary completion
- 1 Jan 2028 (estimated)
- Study completion
- 1 Jan 2030 (estimated)
- First posted
- 8 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Epigenetic changes such as alterations in DNA methylation and histone modification play an important role in the pathophysiology of myelodysplastic syndromes (MDS). With the development of next-generation sequencing (NGS) platforms, it has become possible to identify genomic aberrations involved in the MDS epigenetics. Additionally, with the advances in therapeutic methods in MDS, several novel genomic aberrations have been reported to predict the effectiveness of specific treatment. It is becoming clear that genomic aberrations may offer more precise cancer phenotypes and help predict precise therapies for MDS patients (e.g. IDH1 and IDH2 inhibitors). TET2 gene is a member of the DNA methylation machinery and one of the most frequently mutated genes in MDS and chronic myelomonocytic leukemia (CMML; a disease entity similar to MDS with similar bone marrow dysplasia and accompanying cytopenias). TET DNA dioxygenases hydroxylate 5-methylcytosine (5mC) to 5-hydroxy-mC (5hmC), a process that leads to passive demethylation and thereby initiation of differentiation programs of hematopoietic stem cells (HSCs). TET2 mutations (TET2MT) often act as founder lesions for clonal hematopoiesis of indeterminate potential (CHIP). Our group has demonstrated that mutational exclusivity of TET2 and isocitrate dehydrogenases 1 and 2 (IDH1/2) result from production of a neomorphic natural TET2 inhibitor α-hydroxyglutarate (2HG). 2HG is selectively and synthetically lethal to TET2-deficient HSCs reliant for their survival on minimal residual dioxygenase activity supplied by less abundant TET1 and TET3. This observation inspired the idea of generating TET inhibitors as drugs selective for TET2 mutant (TET2MT) leukemia cells. Based on the structure of 2HG, investigator generated a more potent TETi76, and showed that this drug is indeed synthetically lethal to TET2MT and TET2 proficient cells. In search for alternative agents with suitable activity, investigator next performed a high throughput drug screen using an in vitro DNA dioxygenase assay. Among several hits, eltrombopag (EPAG) was unique, as it is already used in clinical practice as a thrombopoietin receptor (TPOR) agonist. Investigator showed that this agent inhibited growth of TET2MT cells in murine TET2MT models independent of its TPOR activity, and have determined its binding site and mode of action on TET dioxygenases.1 Since EPAG is an FDA approved drug with known toxicities and good tolerability, repurposing this agent as a TET inhibitor would greatly shorten the development time and thus rapidly provide a selective and well-tolerated drug for the therapy of patients with TET2MT MDS. Investigators have obtained granular molecular and response data from historical trials of EPAG/5Azacytidine in unselected MDS and aplastic anemia (AA) and were able to retrospectively assert that indeed those with TET2MT disease responded to EPAG therapy, resulting in decreased TET2MT clonal burden.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Eltrombopag (EPAG) | Experimental | Drug: Eltrombopag (EPAG)Enrolled participants will receive EPAG 50 mg daily, 2h prior to or after meals for 1 cycle |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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:
- 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%.
Key exclusion criteria (17 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Eltrombopag (EPAG)Also: Promacta50 mg, 28-day cycles, 3 initial cycles + 12 cycles on extension arm (maximum of 15 cycles) | Drug | Eltrombopag (EPAG) |
Primary outcome
Response Rate as assessed by hematologic response
Time frame: At end of treatment (approximately up to 12 weeks)
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).
6 secondary outcomes
AML-free survival
Time frame: At end of treatment (approximately up to 12 weeks)
Progression Free Survival
Time frame: At end of treatment (approximately up to 12 weeks)
Change in TET2 mutation burden as measured by variant allele fraction.
Time frame: 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
Time frame: Approximately at 24 weeks post administration of intervention
Rates of robust response as measured by hemoglobin
Time frame: Approximately at 24 weeks post administration of intervention
Rates of robust response as measured by ANC
Time frame: Approximately at 24 weeks post administration of intervention
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2026.
- Individual participant dataSharing planned: Yes. All IPD that underlie results in publication will be shared as a combined summary. Any individual outcomes published per subject will be de- identified utilizing the subject ID (e.g., dosing, demographics, adverse events, etc.)
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Abhay Singh, MD, MPH principal investigator
Case Comprehensive Cancer Center, Cleveland Clinic Taussig Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Eltrombopag (EPAG) in people with Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia, run by Abhay Singh, MD MPH at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: paused, as of the sponsor's last update on 9 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Response Rate as assessed by hematologic response (time frame: At end of treatment (approximately up to 12 weeks)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Oct 2026.