Clinical Trial: Eltrombopag for Inherited Thrombocytopenias

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Eltrombopag for Inherited Thrombocytopenias

Brief Summary:

Inherited thrombocytopenias are a heterogeneous group of disorders characterized by a reduced number of blood platelets and a consequent bleeding tendency that ranges from mild to life-threatening. Thrombocytopenia is caused by genetic mutations and therefore is present throughout patients' life and can be transmitted to the progeny. Some patients with severely reduced platelet count present spontaneous bleedings, which represent a major clinical problem: in fact, bleeding diathesis exposes these subjects to the risk of severe hemorrhages, affects their quality of life and often requires hospitalization and/or transfusions. Conversely, other patients with inherited thrombocytopenias have absent or mild spontaneous bleeding tendency. However, even these patients are at risk of major bleedings on the occasion of surgery or other invasive procedures. Therefore, the potential for hemorrhages on the occasion of invasive procedures represent a clinical problem for all patients affected by inherited thrombocytopenias.

Eltrombopag is a drug, available in tablets, which stimulates the production of platelets by the bone marrow. A previous study demonstrated that a short course of eltrombopag was effective in increasing platelet count in most patients with the MYH9-related disease (MYH9-RD), one form of inherited thrombocytopenia. Eltrombopag was given for 3 to 6 weeks to 12 patients with MYH9-RD and platelet counts lower than 50 x10e9/L. Eleven patients responded to the drug and 8 of them obtained platelet counts higher than 100 x109/L or three times the baseline value. Remission of spontaneous bleeding was achieved by 8 of 10 patients and treatment was well tolerated in all the cases. Based on these findings, short-term eltrombopag courses have been successfully used for preparing for major surgery two patients with MYH9-RD and less than 20 x10e9 platelets/L.

  • platelet count [ Time Frame: 3 or 6 weeks (Phase 1) ]
    Phase 1: major response is defined by increase of platelet count over 100 x10e9/L and no bleeding tendency (grade 0 of the WHO bleeding scale) during the last week of treatment. Minor response is defined by a platelet count that is at least two times the baseline value, but does not reach the criteria for major response and reduction of bleeding tendency according to the WHO bleeding scale during the last week of treatment.
  • bleeding tendency according to the WHO bleeding scale [ Time Frame: 3 or 6 weeks (Phase 1); 16 weeks (Phase 2) ]

    Phase 1: major response is defined by increase of platelet count over 100 x10e9/L and no bleeding tendency (grade 0 of the WHO bleeding scale) during the last week of treatment. Minor response is defined by a platelet count that is at least two times the baseline value, but does not reach the criteria for major response and reduction of bleeding tendency according to the WHO bleeding scale during the last week of treatment.

    Phase 2: Major response is defined by disappearance of bleeding tendency (grade 0 of the WHO bleeding scale) during the last week of treatment. Minor response is defined by any reduction of bleeding tendency according to the WHO bleeding scale during the last week of treatment.



    • Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • daily dose of eltrombopag (in milligrams) required for achievement of the primary endpoints [ Time Frame: 3 or 6 weeks (Phase 1); 16 weeks (Phase 2) ]
    • number of adverse events as a measure of safety and tolerability. [ Time Frame: 7 or 10 weeks (Phase 1); 20 weeks (Phase 2) ]


    Original Secondary Outcome: Same as current

    Information By: IRCCS Policlinico S. Matteo

    Dates:
    Date Received: April 14, 2015
    Date Started: April 2015
    Date Completion: December 2017
    Last Updated: March 1, 2017
    Last Verified: February 2017