Eltrombopag and the Bcl-extra-large (xL) Pathway in Idiopathic Thrombocytopenic Purpura (ITP)
Condition: Immune Thrombocytopenia
MeSH terms: Thrombocytopenia; Purpura, Thrombocytopenic, Idiopathic
Intervention: Eltrombopag; Romiplostim; healthy controls
Intervention description: The 10 subjects will be treated with eltrombopag 75 mg once daily. Patients will be monitored 3 times, weekly, for the first 2 weeks, and then monitored as clinically indicated as they continue eltrombopag dosing for 3-4 months.; three of the patients treated with eltrombopag will be treated with weekly romiplostim at a dose of 10 micrograms/kg weekly for 2 weeks with testing at weekly intervals for 3 times; single blood draw for all measures included in the intervention arms
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Intervention model description: 10 patients on eltrombopag and 3 were then treated with romiplostim 10 healthy controls
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: ITP

Summary:

      The purpose of this study is to further evaluate the effects that eltrombopag (and
      romiplostim) have on platelets in subjects with chronic ITP. Eltrombopag is approved by the
      Food and Drug Administration (FDA) for the treatment of low platelets in patients with
      chronic ITP. It is being further studied by GlaxoSmithKline (now Novartis) in other
      conditions associated with low platelets. This research study is being done because
      eltrombopag has been shown to increase platelet counts in a different way than other
      therapies for ITP. The investigators want to further study how eltrombopag and romiplostim
      affect subjects and their platelets to determine how the study drug should best be used in
      ITP treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subject has signed and dated a written informed consent

          -  Male or female adults (≥18 years) diagnosed with either primary ITP according to the
             American Society for Hematology or British Committee for Standards in Haematology
             (ASH/BCSH) guidelines [Blood, 1996; British Journal of Haematology, 2003] for at least
             three months prior to study entry or with ITP secondary to Evans syndrome, systemic
             lupus erythematosus (SLE), or Common Variable Immunodeficiency (including
             hypogammaglobulinemia).

          -  Subjects must have responded with a platelet count > 30,000/µL to a previous ITP
             therapy including thrombopoietic agents.

          -  Platelet count < 30,000/µL

          -  Female subjects of childbearing potential are practicing an acceptable method of
             contraception or are completely abstinent from intercourse.

        Exclusion Criteria:

          -  Active infection

          -  Previously treated with thrombopoietic agents IF either no response at a therapeutic
             dose (peak platelet count < 50k) OR treatment with the agent within the past 4 weeks

          -  Currently treated with concomitant ITP medication that has not been stable in dose for
             at least 2 weeks - only prednisone, azathioprin, and danazol are allowed.

          -  Female subjects who are nursing or pregnant

          -  Thrombosis of any kind within past 6 months or on blood thinners because of
             thrombosis.

          -  Intravenous Immunoglobulin (IVIG), IV anti-D, bolus corticosteroids or vinca alkaloids
             within the past week

          -  Other cytotoxic or immunosuppressive ITP therapy within the past 8 weeks or rituximab
             within the past 12 weeks

          -  Active non-dermatologic malignancy defined as presence of known tumor ie. visible by
             radiography or evident on blood or bone marrow testing OR receiving chemotherapy
             within past 2 months

          -  Hemoglobin < 10 gm/dl or white blood cell count < 2,500/ul

          -  Liver function tests (ALT, Aspartate Aminotransferase (AST), or total bilirubin) >
             three times upper limit of normal (ULN)

          -  Creatinine > two times upper limit of normal (ULN)