Efficacy and Safety of Eltrombopag In Patients With Severe and Very Severe Aplastic Anemia
Condition: Severe Aplastic Anemia; Very Severe Aplastic Anemia; Moderate Aplastic Anemia
MeSH terms: Anemia; Anemia, Aplastic
Intervention: Eltrombopag
Intervention description: Oral eltrombopag 150mg/day by mouth starting on Day 1 with dose modification over 12 weeks to a maximum of 300mg/day determined by platelet count
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 13.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: severe aplastic anemia; very severe aplastic anemia; moderate aplastic anemia; bleeding

Summary:

      The investigators hypothesis is that eltrombopag given to patients with moderate to very
      severe aplastic anemia will result in an increase in platelet counts. The investigators
      hypothesize that in patients with moderate to very severe aplastic anemia, treatment with
      eltrombopag will lead to fewer platelet transfusions, red blood cell transfusions, and fewer
      bleeding events. The investigators hypothesize that in patients with moderate to very severe
      aplastic anemia, eltrombopag will have an acceptable toxicity rate <3%, at doses that result
      in increased platelet counts. Finally the investigators hypothesize that plasma eltrombopag
      levels in peripheral blood will correlate with improved platelet counts.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Able to provide written informed consent and any other authorizations required by
             local law (e.g., Protected Health Information [PHI])

          -  Have severe or very severe aplastic anemia, or moderate aplastic anemia with platelet
             counts that have dropped below 20,000/μl

          -  Have moderate, severe, or very severe aplastic anemia with moderate bleeding during or
             after a surgical procedure, (including bone marrow biopsy, lumbar puncture,
             thoracentesis, paracentesis, port placement, dermal biopsy) or minimal mucocutaneous
             bleeding otherwise noted

          -  Subjects with current or previous exposure to approved medications for the treatment
             of aplastic anemia will not be excluded; these include but may not be limited to,
             anti-thymocyte globulin (ATG), cyclosporine, corticosteroids, and G-CSF.

        Exclusion Criteria:

          -  Have diagnosis of Fanconi anemia

          -  Have infection not adequately responding to appropriate therapy

          -  Have Paroxysmal Nocturnal Hemoglobinuria (PNH) clone size in neutrophils of greater
             than or equal to 50%

          -  Have known HIV positivity

          -  Have creatinine and/or blood urea nitrogen (BUN) ≥2 times the upper limit of normal

          -  Have serum bilirubin ≥ 1.5 times the upper limit of normal, or ≥4.0 times the upper
             limit of normal if the patient has been treated with ATG within three weeks of
             screening.

          -  Have AST and/or ALT ≥ 3 times the upper limit of normal

          -  Have hypersensitivity to eltrombopag or its components

          -  Have chemotherapy given less than or equal to 14 days prior to initiating the study
             medication. This does not include immunosuppressive agents and growth factor as
             described above

          -  Are female and are nursing or pregnant or are unwilling to take oral contraceptives or
             refrain from pregnancy if of childbearing potential

          -  Are unable to understand the investigational nature of the study or give informed
             consent

          -  Have a history of arterial or venous thrombosis within the last 1 year (excluding
             those due to indwelling lines)

          -  Have an ECOG performance status of 3 or greater

          -  Have had treatment with Campath within 6 months of entry into the study

          -  Have pre-existing cardiovascular disease (congestive heart failure with New York Heart
             Association [NYHA] grade III/IV), arrhythmia known to increase the risk of
             thromboembolic events (e.g. atrial fibrillation), unstable angina, or QTc > 450 msec
             (QTc 480 msec for subjects with bundle branch block), or myocardial infarction within
             the preceding 6 months) at study entry

          -  Have had other TPO-R agonists medication in the previous 4 weeks.