Eltrombopag for Preleukemia

Overseen By Abhay Singh, MD, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Case Comprehensive Cancer Center

Must not be taking: Anticoagulants

Disqualifiers: High-risk MDS, CMML 1-2, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called eltrombopag (also known as Promacta or Revolade) to determine if it can improve blood cell counts in people with certain blood disorders, specifically low-risk Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML) with a specific DNA change in the TET2 gene. The goal is to see if eltrombopag can increase platelets (tiny blood cells that help with clotting) and improve the condition over time. This trial may suit those diagnosed with these conditions, who have TET2 mutations, and have not responded well to other treatments. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people, offering a chance to contribute to important findings.

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

Is there any evidence suggesting that eltrombopag is likely to be safe for humans?

Research has shown that eltrombopag is generally safe for patients with low-risk Myelodysplastic Syndromes (MDS). One study found it effective and relatively safe for patients with severe thrombocytopenia, a condition characterized by low platelet counts in the blood.

The FDA has already approved eltrombopag for treating conditions like severe aplastic anemia and low platelet levels in immune thrombocytopenia (ITP) and chronic hepatitis C. This approval suggests that its safety is well-understood for these conditions, which is promising for its potential use in MDS and Chronic Myelomonocytic Leukemia (CMML).

However, in some cases, about 30-65% of patients experienced low platelet levels. While eltrombopag has been beneficial for some, it can still cause blood-related issues. Participants should discuss these safety findings with their doctors to understand what they might mean personally. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for preleukemia?

Eltrombopag is unique because it offers a novel approach for treating preleukemia by stimulating the production of platelets. Unlike traditional treatments for preleukemia, which often involve supportive care or medications that address symptoms, Eltrombopag directly targets platelet production. This is particularly exciting for researchers because it could reduce the need for platelet transfusions and improve quality of life for patients. Moreover, Eltrombopag is taken orally, which is more convenient compared to treatments that require intravenous administration.

What evidence suggests that eltrombopag might be an effective treatment for preleukemia?

Studies have shown that eltrombopag can benefit people with low-risk Myelodysplastic Syndromes (MDS) who have very low platelet counts. In one study, 47% of patients taking eltrombopag experienced improved platelet levels within 24 weeks. This improvement is crucial because platelets aid in blood clotting, reducing the risk of bleeding. Eltrombopag increases platelet production and has not been shown to promote cancer cell growth in MDS or acute myeloid leukemia. Overall, research has found eltrombopag to be effective and relatively safe for patients with low-risk MDS. Participants in this trial will receive eltrombopag as part of the study treatment. ^{3 5 6 7 8}

Who Is on the Research Team?

Abhay Singh, MD, MPH

Principal Investigator

Case Comprehensive Cancer Center, Cleveland Clinic Taussig Cancer Institute

Are You a Good Fit for This Trial?

This trial is for patients with low-risk MDS or CMML who have mutations in the TET2 gene. It's designed to see if eltrombopag can improve their blood cell counts. Participants must meet specific health criteria, but those details are not provided here.

Inclusion Criteria

My cancer has a TET2 mutation of more than 2%.

I have previously been treated with medications like darbepoetin or epoetin alfa.

Willing and able to adhere to the study visit schedule and other protocol requirements

Exclusion Criteria

I had cancer in the last 5 years with a high risk of it coming back.

I have been treated with hypomethylating agents before.

I have had blood clots and am taking blood thinners.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Eltrombopag 50 mg daily for 1 cycle

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Eltrombopag

Trial Overview The study tests whether eltrombopag, approved for other blood conditions, can be effective in treating low-risk MDS and CMML with TET2 mutations by improving blood cell counts and observing genetic changes over time.

How Is the Trial Designed?

Group I: Eltrombopag (EPAG) Experimental Treatment 1 Intervention

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

Eltrombopag is already approved in United States, European Union, Canada, Japan, China for the following indications:

Approved in United States as Promacta for:

• Severe aplastic anemia
• Chronic immune thrombocytopenia
• Thrombocytopenia in patients with chronic hepatitis C

Approved in European Union as Revolade for:

• Severe aplastic anemia
• Chronic immune thrombocytopenia

Approved in Canada as Promacta for:

• Severe aplastic anemia
• Chronic immune thrombocytopenia

Approved in Japan as Revolade for:

• Severe aplastic anemia
• Chronic immune thrombocytopenia

Approved in China as Promacta for:

• Severe aplastic anemia
• Chronic immune thrombocytopenia

Who Is Running the Clinical Trial?

Case Comprehensive Cancer Center

Lead Sponsor

Trials

472

Recruited

33,400+

Abhay Singh, MD MPH

Lead Sponsor

Trials

1

Recruited

30+

Published Research Related to This Trial

Eltrombopag is an effective treatment for patients with severe aplastic anemia who do not respond to immunosuppressive therapy, showing a hematological response in at least 40% of patients after 12-16 weeks of treatment.

The drug works by stimulating hematopoietic stem cells and increasing platelet, red blood cell, and neutrophil counts, while being generally well tolerated, though it can cause increased liver transaminases and some cytogenetic abnormalities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eltrombopag: a review of its use in patients with severe aplastic anaemia. McCormack, PL.[2018]

Eltrombopag is an effective treatment for pediatric patients aged 1-17 years with chronic immune thrombocytopenia (ITP), showing significantly higher platelet response rates compared to placebo in phase II and III trials.

In long-term therapy, eltrombopag maintained platelet counts above 50 × 10^9/L for most patients, allowing about half of them to reduce or stop other ITP medications, and it was generally well tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eltrombopag: A Review in Paediatric Chronic Immune Thrombocytopenia. Burness, CB., Keating, GM., Garnock-Jones, KP.[2022]

Eltrombopag, an oral medication for chronic idiopathic thrombocytopenic purpura (ITP), showed that about 25% of patients achieved a platelet count of at least 50,000/mm3, but it did not significantly reduce bleeding frequency compared to placebo in a study of 114 patients.

Romiplostim is considered a more effective option than eltrombopag for ITP, especially when standard treatments fail, as eltrombopag carries a higher risk of non-haematological side effects and potential drug interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eltrombopag. Idiopathic thrombocytopenic purpura after treatment failure: romiplostim is a better option. [2016]

Eltrombopag is an effective treatment for increasing platelet counts in adults with chronic hepatitis C virus (HCV) infection, enabling 95% of patients to start peginterferon-based antiviral therapy who otherwise would not qualify due to low platelet levels.

While eltrombopag improved the likelihood of achieving a sustained virological response after treatment compared to placebo, the additional benefit was modest (less than 10%), and it carries risks of serious side effects like hepatic decompensation and thromboembolic events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eltrombopag: a review of its use in the treatment of thrombocytopenia in patients with chronic hepatitis C. Burness, CB.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10552995/

Eltrombopag for Low-Risk Myelodysplastic Syndromes With ... Overall, the combined outcome AML evolution and/or disease progression occurred in 19 of 111 (17%) eltrombopag patients versus nine of 54 (17%) ...

2. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.22.02699

Eltrombopag for Low-Risk Myelodysplastic Syndromes ... Eltrombopag was effective and relatively safe in low-risk MDS with severe thrombocytopenia. This trial is registered with ClinicalTrials.gov ...

3. karger.com karger.com/aha/article/146/5/373/843804/Long-Term-Safety-and-Efficacy-of-Eltrombopag-for

Long-Term Safety and Efficacy of Eltrombopag for ... Approximately 30–65% of patients in this open-label extension phase experienced clinically relevant thrombocytopenic events; no conclusions could be made ...

4. ashpublications.org ashpublications.org/ashclinicalnews/news/3026/Efficacy-of-Eltrombopag-in-Patients-With-Lower

Efficacy of Eltrombopag in Patients With Lower-Risk ... In the eltrombopag cohort, the proportion of patients who achieved platelet responses within 24 weeks (primary endpoint) was 47 percent (n=28), ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02928419?term=AREA%5BBasicSearch%5D(promacta%20mds)&rank=10

Efficacy of Eltrombopag Plus Lenalidomide Combination ... It has been shown that in patients affected by MDS and by acute myeloid leukemia, Eltrombopag neither increases the proliferation, nor the clonogenic growth ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37231838/

Long-Term Safety and Efficacy of Eltrombopag for ... Approximately 30-65% of patients in this open-label extension phase experienced clinically relevant thrombocytopenic events; no conclusions could be made ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.22.02699

Eltrombopag for Low-Risk Myelodysplastic Syndromes ... Eltrombopag was effective and relatively safe in low-risk MDS with severe thrombocytopenia. This trial is registered with ClinicalTrials.gov ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT01286038

Eltrombopag in Myelodysplastic Syndrome (MDS) Patients ... The purpose of this study is to evaluate the safety and efficacy of eltrombopag in people who have myelodysplastic syndrome (MDS) with thrombocytopenia who have ...