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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether the drug eltrombopag (also known as Promacta or Revolade) can improve blood cell counts in individuals with Fanconi anemia, a genetic condition that often reduces blood cell levels. The research aims to determine if eltrombopag can boost these counts and the duration required for noticeable effects. Candidates for the trial include those with Fanconi anemia and low blood cell counts who have not responded to or declined androgen treatment and can take pills. Participants will take the drug daily for 24 weeks and undergo regular blood tests to monitor progress. If blood counts improve, treatment may continue for up to three years. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research has shown that eltrombopag has been tested in people with Fanconi anemia. These studies found the drug to be generally safe, though some side effects were noted. The most common issues involved the stomach and liver, leading to dose reductions for some participants. Specifically, in one study, 3 out of 8 patients required dose adjustments due to these side effects.

Eltrombopag is already used for other blood conditions, so its safety profile is well understood. However, when exploring new uses for a drug, careful monitoring remains essential to ensure safety. Participants in these studies undergo regular checks to catch any problems early. ^{1 2 3 4 5}

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

Eltrombopag is unique because it works by stimulating platelet production, which can be particularly beneficial for individuals with Fanconi Anemia who struggle with low blood cell counts. Unlike standard treatments that primarily focus on managing symptoms or complications, Eltrombopag directly targets the underlying issue of insufficient platelet production. Researchers are excited about this treatment because it offers a novel approach that could improve blood cell levels and potentially reduce the need for transfusions.

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

Research has shown that eltrombopag, the treatment under study in this trial, can increase blood counts in individuals with bone marrow issues, such as those seen in Fanconi anemia. Studies have found that eltrombopag stimulates hematopoiesis, the production of blood cells, and might also repair damaged DNA in these cells. In past patients with similar conditions, eltrombopag raised platelet counts, reducing their need for transfusions. This suggests that eltrombopag could benefit people with Fanconi anemia by increasing blood cell counts and potentially improving overall health. ^{1 2 4 5 6}

Who Is on the Research Team?

Andre Larochelle, M.D.

Principal Investigator

National Heart, Lung, and Blood Institute (NHLBI)

Are You a Good Fit for This Trial?

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

You have a history of abusing alcohol or drugs.

Concurrent participation in an investigational study within 30 days prior to enrollment or within 5-half-lives of the investigational product, whichever is longer

I cannot take medicine by mouth.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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 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]

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]

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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40665878/

Eltrombopag for Bone Marrow Failure in Fanconi Anemia Eltrombopag stimulates hematopoiesis in aplastic anemia, and preclinical studies suggest it promotes DNA repair in Fanconi Anemia (FA) hematopoietic stem cells.

2. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/ejh.70007?af=R

Eltrombopag for Bone Marrow Failure in Fanconi Anemia: ... Eltrombopag stimulates hematopoiesis in aplastic anemia, and preclinical studies suggest it promotes DNA repair in Fanconi Anemia (FA) ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03206086

Eltrombopag for People With Fanconi Anemia Peripheral blood platelet count increases to 20,000/microliter above baseline at six months or stable platelet counts with transfusion independence, an increase ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12375905/

Eltrombopag in mosaic and gene therapy-treated patients with ... It has been demonstrated that eltrombopag stimulates trilineage hematopoiesis in aplastic anemia, and preclinical studies suggest it promotes ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06045052?cond=Fanconi%20anemia,%20complementation%20group%20A&viewType=Table&rank=8

Eltrombopag for Treatment of Fanconi Anemia An open-label, phase II study to assess the efficacy and safety of eltrombopag for the treatment of children and adolescents with Fanconi anemia. Detailed ...

6. ashpublications.org ashpublications.org/blood/article/134/Supplement_1/3753/424209/Phase-II-Study-of-Eltrombopag-in-Subjects-with

Phase II Study of Eltrombopag in Subjects with Fanconi Anemia The primary safety endpoint is the toxicity profile assessed at 6 months using the CTCAE criteria. Sample Size and Statistical Methods. Simon's ...