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

Trial Summary

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.

What data supports the effectiveness of the drug Eltrombopag for preleukemia?

Eltrombopag has been shown to increase platelet counts and improve blood cell production in conditions like severe aplastic anemia and chronic immune thrombocytopenia, suggesting it may help in managing blood cell deficiencies in preleukemia. ^{1 2 3 4 5}

How does the drug Eltrombopag differ from other treatments for preleukemia?

Eltrombopag is unique because it is primarily used to increase platelet production, which may help manage low platelet counts in preleukemia, whereas other treatments for related conditions like acute promyelocytic leukemia focus on chemotherapy and retinoic acid to target cancer cells directly. ^{6 7 8 9 10}

What is the purpose of this trial?

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.

Research Team

Abhay Singh, MD, MPH

Principal Investigator

Case Comprehensive Cancer Center, Cleveland Clinic Taussig Cancer Institute

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

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

2. New Zealand pubmed.ncbi.nlm.nih.gov

Eltrombopag: A Review in Paediatric Chronic Immune Thrombocytopenia. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

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

4. Italy pubmed.ncbi.nlm.nih.gov

The European Medicines Agency review of eltrombopag (Revolade) for the treatment of adult chronic immune (idiopathic) thrombocytopenic purpura: summary of the scientific assessment of the Committee for Medicinal Products for Human Use. [2021]

5. France pubmed.ncbi.nlm.nih.gov

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

6. England pubmed.ncbi.nlm.nih.gov

Treatment of acute promyelocytic leukemia: strategy toward further increase of cure rate. [2013]

7. Germany pubmed.ncbi.nlm.nih.gov

Disseminated intravascular coagulation in acute promyelocytic leukemia. Possibility of treatment with glucocorticoids at high doses. [2013]

8. Switzerland pubmed.ncbi.nlm.nih.gov

epsilon-Amino-caproic acid in the management of acute promyelocytic leukaemia. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

Acute tumor lysis syndrome in prolymphocytic leukemia. [2015]

10. Japan pubmed.ncbi.nlm.nih.gov

Long-term survival and prognostic study in acute promyelocytic leukemia treated with all-trans-retinoic acid, chemotherapy, and As2O3: an experience of 120 patients at a single institution. [2018]