efficacy and safety of eltrombopag in patients with severe and very severe aplastic anemia

Conditions: Severe Aplastic Anemia; Very Severe Aplastic Anemia; Moderate Aplastic Anemia

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.

Keywords: severe aplastic anemia very severe aplastic anemia moderate aplastic anemia bleeding