Efficacy of Eltrombopag to Improve Thrombocytopenia of MYH9-related Disease
Condition: Blood Platelet Disorders
MeSH terms: Thrombocytopenia; Blood Platelet Disorders
Intervention: eltrombopag
Intervention description: Eltrombopag, administered orally, 50 mg/daily for 21 days. Patients with platelet counts between 100 and 150x10e9/L at day 21 will continue eltrombopag 50 mg/daily for 21 additional days. Patients with platelet count lower than 100x10e9/L at day 21 will receive eltrombopag 75 mg/daily for additional 21 days. Patients with more than 150x10e9 platelets/L at day 21 will stop therapy.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 16 Years
Healthy volunteers: No
Keywords: inherited thrombocytopenia; MYH9 mutations; eltrombopag

Summary:

      The term MYH9-related disease (MYH9RD) includes four genetic disorders: May-Hegglin anomaly,
      Sebastian syndrome, Fechtner syndrome, and Epstein syndrome. All these disorders derive from
      mutation of a unique gene, named MYH9, and they have been recognized as different clinical
      presentations of a single illness that was named MYH9RD. All patients affected by MYH9RD
      present since birth with thrombocytopenia, which can result in a variable degree of bleeding
      diathesis; some of them subsequently develop additional clinical manifestations, such as
      renal damage, sensorineural hearing loss, and/or presenile cataracts. Eltrombopag is an oral
      thrombopoietin receptor agonist that stimulates proliferation and differentiation of
      megakaryocytes, the bone marrow cells that produce blood platelets. This drug is effective in
      increasing platelet count in healthy volunteers, as well as in patients affected by some
      acquired thrombocytopenias, such as idiopathic thrombocytopenic purpura and HCV related
      thrombocytopenia. The purpose of this study is to determine if eltrombopag, administered
      orally at the dose of 50 or 75 mg/daily for up to 6 weeks, is effective in increasing
      platelet count of patients affected by MYH9RD. Further aims of this study are to test if
      eltrombopag is effective in reducing bleeding tendency of MYH9RD patients; to evaluate safety
      and tolerability of eltrombopag in patients with MYH9RD; to evaluate in vitro function of
      platelets produced during therapy in patients responding to this drug.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age 16 years or more

          -  Confirmed diagnosis of MYH9-related disease

          -  Average platelet count for the previous year less than 50x10e9/L

          -  Written informed consent

        Exclusion Criteria:

          -  Diseases known to involve the risk of thromboembolic events (e.g. atrial fibrillation)

          -  History of thrombosis within 1 year

          -  Use of drugs that affect platelet function (including but not limited to, aspirin,
             clopidogrel or NSAIDS) or anti-coagulants

          -  Females who are pregnant or nursing (a negative pregnancy test in required before
             enrollment of fertile women)

          -  Formal refusal of any recommendation of a safe contraception

          -  Alcohol or drug addiction

          -  Altered renal function as defined by creatinine of 20 mg/L or more

          -  Any other disease or condition that by the advise of the responsible physician would
             make the treatment dangerous for the patient or would make the patient ineligible for
             the study, including physical, psychiatric, social and behavioral problems. HCV
             positivity and liver diseases will not be considered an exclusion criterion since a
             phase II study showed that eltrombopag was effective and safe in this patient
             population.