Eltrombopag for Fanconi Anemia

Overseen By Bretagne Cowling, R.N.

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Must not be taking: Androgens

Disqualifiers: Infections, MDS, AML, malignancy, 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: 4

Duration: 24 weeks

25 Participants Needed

Trial Summary

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

The trial protocol does not specify if you need to stop taking your current medications. However, you must not have taken androgens like danazol or oxymetholone within 4 weeks before starting eltrombopag.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must not have taken androgens like danazol or oxymetholone in the 4 weeks before starting the study drug.

What data supports the idea that Eltrombopag for Fanconi Anemia is an effective treatment?

The available research shows that Eltrombopag can be effective for Fanconi Anemia. In one case, it was used alongside another drug, oxymetholone, and helped improve blood cell production in three different types of blood cells. This improvement meant the patient no longer needed blood transfusions before undergoing a stem cell transplant, which is a major treatment for Fanconi Anemia. This suggests that Eltrombopag can help manage the condition and improve outcomes when combined with other treatments. ^{1 2 3 4 5}

What evidence supports the effectiveness of the drug Eltrombopag for treating Fanconi Anemia?

Eltrombopag has been shown to help increase blood cell production in conditions like severe aplastic anemia and chronic immune thrombocytopenia, which are similar to the blood cell issues seen in Fanconi Anemia. In one case, Eltrombopag, combined with another drug, helped a Fanconi Anemia patient improve blood cell counts and reduce the need for transfusions before a stem cell transplant. ^{1 2 3 4 5}

What safety data exists for Eltrombopag in treating Fanconi Anemia?

The provided research does not contain safety data for Eltrombopag (also known as Promacta or Revolade) in the treatment of Fanconi Anemia. The studies focus on the adverse effects of all-trans retinoic acid (ATRA) in acute promyelocytic leukemia, which is unrelated to Eltrombopag or Fanconi Anemia. ^{6 7 8 9 10}

Is the drug Eltrombopag a promising treatment for Fanconi Anemia?

Eltrombopag is a promising drug because it helps increase platelet counts, which are important for blood clotting. It has been effective in treating other conditions with low platelet counts, like chronic immune thrombocytopenia and severe aplastic anemia, by boosting blood cell production. This suggests it could be beneficial for Fanconi Anemia, which also involves blood cell issues. ^{1 2 3 4 11}

How is the drug eltrombopag unique in treating Fanconi Anemia?

Eltrombopag is unique because it is an oral drug that stimulates platelet production by activating thrombopoietin receptors, which is different from other treatments that may involve more invasive procedures like blood transfusions or bone marrow transplants. It is also used in other conditions to increase platelet counts, making it a novel option for managing blood cell deficiencies in Fanconi Anemia. ^{1 2 3 4 11}

What is the purpose of this trial?

Background: Fanconi anemia is a genetic disease. Some people with it have reduced blood cell counts. This means their bone marrow no longer works properly. These people may need blood transfusions for anemia (low red blood cells) or low platelet counts or bleeding. Researchers want to see if a new drug will help people with this disease. Objective: To find out if a new drug, eltrombopag, is effective in people with Fanconi anemia. To know how long the drug needs to be given to improve blood counts. Eligibility: People at least 6 years old with Fanconi anemia with reduced blood cell counts. Design: Participants will be screened with blood and urine tests. They will repeat this before starting to take the study drug. Participants will take eltrombopag pills by mouth once a day for 24 weeks. They will be monitored closely for side effects. Participants will have blood tests every 2 weeks while on eltrombopag. Participants will visit NIH 3 months and 6 months after starting eltrombopag. At these visits, participants will: Answer questions about their medical history, how they are feeling, and their quality of life Have a physical exam Have blood and urine tests Have a bone marrow sample taken by needle from the hip. The area will be numbed. If participants blood cell counts improve, they might join the extended access part of the study. They will continue taking eltrombopag for 3 years and sign a different consent. After 24 weeks of treatment, if there is no improvement in blood cell counts, participants will stop taking eltrombopag. They will return for an optional follow-up visit that repeats the study visits....

Research Team

Andre Larochelle, M.D.

Principal Investigator

National Heart, Lung, and Blood Institute (NHLBI)

Eligibility Criteria

This trial is for people aged 2 or older with Fanconi anemia who have low blood cell counts and weigh over 10kg. They should not have had recent cancer, thromboembolic events, HIV, certain genetic mutations, severe illnesses that could affect the drug's tolerance, or be on other investigational drugs.

Inclusion Criteria

I am at least 2 years old.

I have been diagnosed with Fanconi anemia through genetic testing or chromosome analysis.

I have low blood counts or need regular blood transfusions.

Exclusion Criteria

I cannot take medicine by mouth.

I have a heart condition that could make participating in the study unsafe.

You have a history of abusing alcohol or drugs.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants take eltrombopag pills by mouth once a day for 24 weeks and are monitored closely for side effects

24 weeks

Blood tests every 2 weeks, visits at 3 and 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 optional visit (in-person)

Extension

Participants with improved blood cell counts may continue taking eltrombopag for 3 years

3 years

Treatment Details

Interventions

• Eltrombopag

Trial Overview The study tests eltrombopag effectiveness in improving blood counts for those with Fanconi anemia. Participants take eltrombopag daily for 24 weeks and are monitored through regular visits and blood tests. If successful, they may continue treatment up to three years.

Participant Groups

Group I: Group Experimental Treatment 1 Intervention

Eltrombopag

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?

National Heart, Lung, and Blood Institute (NHLBI)

Lead Sponsor

Trials

3,987

Recruited

47,860,000+

Findings from Research

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 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 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, 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]

In a case of Fanconi anemia, the combination of eltrombopag and oxymetholone successfully induced trilineage hematopoiesis, which means it stimulated the production of red blood cells, white blood cells, and platelets.

This treatment eliminated the need for blood transfusions prior to hematopoietic stem cell transplant, potentially improving the patient's outcome after the transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trilineage Hematopoiesis Induced by Low-dose Eltrombopag in a Patient With Fanconi Anemia can be Used as a Bridge to Hematopoietic Stem Cell Transplant. Gupta, A., Palassery, R., Meyerson, H., et al.[2019]

All-trans retinoic acid (RA) can cause several rare adverse effects in patients with acute promyelocytic leukemia (APL), including hypercalcemia, male infertility, and thromboembolic events, highlighting the need for careful monitoring during treatment.

While RA can induce complete remission in some cases of leukemia, its efficacy appears limited, as demonstrated by a response in only one case of M2 leukemia during a third relapse, emphasizing the importance of early diagnosis and management of adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rare but important adverse effects of all-trans retinoic acid in acute promyelocytic leukemia and their management. Hatake, K., Uwai, M., Ohtsuki, T., et al.[2019]

In a multi-institutional study in Japan, tretinoin (ATRA) was highly effective for treating refractory and relapsed acute promyelocytic leukemia, achieving complete remission in 81.5% of previously untreated patients who could not tolerate chemotherapy.

While side effects were common (87.8% of patients experienced issues like skin dryness and headaches), they were generally well tolerated, and serious complications like retinoic acid syndrome were managed effectively, allowing for continued treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Co-operative study of all-trans retinoic acid as a differentiation induction therapy of acute promyelocytic leukemia]. Yamada, O., Hatake, K., Tanimoto, M., et al.[2013]

ATRA (all-trans retinoic acid) is commonly used in combination with anthracyclin-based regimens to treat acute promyelocytic leukemia (APL), but it can cause adverse effects, including myositis.

The case of an 11-year-old girl illustrates that ATRA-induced myositis, while rare, can occur during treatment for APL, highlighting the need for awareness of this potential side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

All-trans-retinoic acid-induced myositis in a child with acute promyelocytic leukemia. Citak, FE., Ezer, U., Akkaya, E., et al.[2013]

Acute promyelocytic leukaemia (APL) has a high cure rate of 85-95% with treatments like arsenic trioxide (ATO) and all-trans-retinoic acid (ATRA), but these treatments can lead to significant early complications and side effects.

The abstract highlights two cases of genital vasculitis occurring in patients receiving ATRA and ATO therapy, despite the use of prophylactic steroids, indicating that ATRA can cause rare but serious adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genital vasculitis secondary to all-trans-retinoic-acid. Yanamandra, U., Khadwal, A., Saikia, UN., et al.[2019]

All-transretinoic acid (ATRA) combined with chemotherapy significantly improves remission rates and survival in patients with acute promyelocytic leukemia (APL) by promoting the differentiation of abnormal cells into mature granulocytes.

However, ATRA can cause serious side effects, including pancarditis, as demonstrated in a case of a 9-year-old girl who developed this condition during treatment, highlighting the need for careful monitoring and management of ATRA-related adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

All-transretinoic acid (ATRA) treatment-related pancarditis and severe pulmonary edema in a child with acute promyelocytic leukemia. Işık, P., Çetin, I., Tavil, B., et al.[2022]

Eltrombopag is an effective oral treatment for adults with chronic primary immune thrombocytopenia (ITP), significantly increasing platelet counts and reducing bleeding incidents compared to placebo in trials lasting 6 weeks to 6 months.

While generally well tolerated, eltrombopag may cause mild and reversible hepatobiliary abnormalities, and further research is needed to assess potential risks like thromboembolic events and cataracts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spotlight on eltrombopag in treatment-refractory chronic primary immune thrombocytopenia. Garnock-Jones, KP.[2016]

References

1. 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]

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 patients with severe aplastic anaemia. [2018]

4. France pubmed.ncbi.nlm.nih.gov

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

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

Trilineage Hematopoiesis Induced by Low-dose Eltrombopag in a Patient With Fanconi Anemia can be Used as a Bridge to Hematopoietic Stem Cell Transplant. [2019]

6. Japan pubmed.ncbi.nlm.nih.gov

Rare but important adverse effects of all-trans retinoic acid in acute promyelocytic leukemia and their management. [2019]

7. Japan pubmed.ncbi.nlm.nih.gov

[Co-operative study of all-trans retinoic acid as a differentiation induction therapy of acute promyelocytic leukemia]. [2013]

8. Italy pubmed.ncbi.nlm.nih.gov

All-trans-retinoic acid-induced myositis in a child with acute promyelocytic leukemia. [2013]

9. England pubmed.ncbi.nlm.nih.gov

Genital vasculitis secondary to all-trans-retinoic-acid. [2019]

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

All-transretinoic acid (ATRA) treatment-related pancarditis and severe pulmonary edema in a child with acute promyelocytic leukemia. [2022]

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

Spotlight on eltrombopag in treatment-refractory chronic primary immune thrombocytopenia. [2016]