Treatment of Refractory Diamond-Blackfan Anemia With Eltrombopag

    Not Recruiting
  • End date
    Jun 30, 2027
  • participants needed
  • sponsor
    National Heart, Lung, and Blood Institute (NHLBI)
Updated on 14 September 2022
cell counts



Diamond-Blackfan anemia (DBA) is treated with steroids. But some people cannot take steroids, or steroids don t work. Other patients must get blood transfusions regularly which are time consuming and can have significant side effects. The drug eltrombopag can increase red blood cells. Researchers want to see if it can help people with DBA and, if so, for how long.


To study the safety and efficacy of eltrombopag in people with DBA who have not responded to steroids or could not take them.


People ages 2 and older with DBA who did not respond to steroids or could not take them, or their disease has returned despite taking them


Participants will be screened with:

Medical and medicine history

Physical exam

MRI: Participants will lie in a machine that takes pictures of the liver.

Blood and urine tests

Bone marrow biopsy: A thin needle will remove a marrow sample from the participant s hip bone.


Participants will take eltrombopag pills once daily for 24 weeks. They will have blood taken every 2 weeks.

Participants will have visits 6 months. At 6 months, they will repeat all the screening tests and also have:

Quality-of-life questionnaire

Neurodevelopmental test (for participants younger than 18 years)

If participants blood cell counts improve, they may keep taking eltrombopag for up to 3 more years. If so, they will have blood taken every 4 weeks. They will visit NIH every 6 months and repeat the above tests.

Participants will be monitored for up to 3 years after they stop taking eltrombopag. They will visit NIH 6 months after treatment ends. If participants blood counts go down after treatment ends, they may restart the drug....


Diamond-Blackfan anemia (DBA) is a heritable bone marrow failure (BMF) syndrome characterized by selective erythroid defects typically presenting within the first year of life as a normochromic, macrocytic anemia with reticulocytopenia. More than half of all DBA cases are associated with either inherited or spontaneous mutations in ribosomal proteins, making DBA a prototypic ribosomopathy . Furthermore, although the primary presentation is isolated anemia, as life expectancy has improved, progressive defects in other lineages have now been identified, consistent with a long-term stem cell defect. Current standard of care for DBA is the use of systemic corticosteroids, the mechanism of which is unclear, although only half show an initial response. Even when a response to steroids is observed, long-term steroid therapy carries significant morbidity, especially in children or in combination with transfusion-associated iron overload, and thus most cannot tolerate high-dose steroids long-term. Responses are rare with second-line immunomodulatory agents. Yet other than allogeneic hematopoietic stem cell transplantation in those patients with healthy matched donors, there are no alternative therapies.

In one model for DBA pathogenesis, the defects lead to an overabundance of the iron-carrying moiety heme in primitive erythroid cells, unbound by protein. Free heme is toxic to cells, likely exacerbated over time by iron overload due to transfusions. Ongoing work with eltrombopag (EPAG) has shown that it is capable of acting as a potent iron chelator, including intracellular iron, with evidence that this effect of EPAG can reverse the impact of excess heme and elevated reactive oxygen species. Furthermore, in a recent trial of EPAG for moderate aplastic anemia or hypoproliferative unilineage cytopenias, we identified a robust response to EPAG in the one DBA patient enrolled in this clinical trial. This response has been durable over more than three years since study entry, but requires continuous EPAG to maintain transfusion independence. From these data, we hypothesize that EPAG may be able to improve production of red blood cells in DBA patients via chelation of iron and subsequent reduction in heme synthesis, resulting in decreased toxicity to bone marrow stem cells and developing erythroid cells.

We will conduct a single-arm, pilot trial in patients with steroid-refractory or steroid-intolerant DBA, treating with a fixed dose of EPAG for 6 months to assess safety and efficacy at improving hematological manifestations of DBA. Responders at 6 months will be able to continue EPAG on the extension part of this protocol for an additional 3 years. We will examine the hematologic, molecular, cytogenetic and clonal responses to EPAG in responders and non-responders alike. Translational studies will examine the mechanism of activity of EPAG in DBA through its effects on iron metabolism, erythroid differentiation, apoptosis, global transcriptome and TPO signaling pathways in patient s hematopoietic stem and progenitor cells (HSPCs).

Condition Anemia, Diamond-Blackfan
Treatment Eltrombopag
Clinical Study IdentifierNCT04269889
SponsorNational Heart, Lung, and Blood Institute (NHLBI)
Last Modified on14 September 2022

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