Eltrombopag for Moderate Aplastic Anemia
Condition: Moderate Aplastic Anemia; Unilineage Bone Marrow Failure Disorders
MeSH terms: Anemia; Anemia, Aplastic; Bone Marrow Failure Disorders; Pancytopenia
Intervention: Eltrombopag
Intervention description: Eltrombopag will be administered for 16 to 20 weeks at a starting dose of 150mg/day (East Asian ancestry 75mg /day). The dose will decreased and increased (maximum dose 300mg/day) based on safety and response.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 34.0
Sex: All
Minimum age: 2 Years
Maximum age: 100 Years
Healthy volunteers: No
Keywords: Autoimmunity; Neutropenia; Cytokine; Hematopoiesis; Thrombocytopenia; Aplastic Anemia

Summary:

      Background:

        -  Moderate aplastic anemia is a blood disease which may require frequent blood and
           platelet transfusions. Sometimes patients with this disease can be treated with
           immunosuppressive drugs. Not all patients respond and not all patients are suitable for
           this treatment.

        -  Thrombopoietin (TPO) is a protein made by the body. The bone marrow needs TPO to produce
           platelets. TPO may also be able to stimulate bone marrow stem cells to produce red cells
           and white cells. However, TPO cannot be given by mouth. This has led researchers to
           develop the drug eltrombopag, which acts in the same way and can be given by mouth.
           Eltrombopag has been shown to safely increase platelet numbers in healthy volunteers and
           in patients with other chronic blood diseases, including severe aplastic anemia.
           Researchers are interested in looking at whether eltrombopag can be given to people with
           moderate aplastic anemia and significantly low blood cell counts.

      Objectives:

      - To evaluate the safety and effectiveness of eltrombopag in people with moderate aplastic
      anemia or patients with bone marrow failure and unilineage cytopenia who need treatment for
      significantly low blood cell counts.

      Eligibility:

      - People at least 2 years of age who have moderate aplastic anemia or bone marrow failure and
      unilineage cytopenia,and significantly low blood cell counts.

      Design:

        -  Patients will be screened with a physical examination, medical history, blood tests, a
           bone marrow biopsy, and an eye exam.

        -  Patients will receive eltrombopag by mouth once a day.

        -  Patients will have weekly blood tests to monitor the effectiveness of the treatment and
           adjust the dose in response to possible side effects.

        -  Patients may continue to take eltrombopag if their platelet count or hemoglobin
           increases, their requirement for platelet or blood transfusion decreases after 16 to 20
           weeks of treatment, and there have been no serious side effects. Access to the drug will
           continue until the study is closed. Patients will be asked to return for a follow-up
           visit 6 months after the last dose of medication.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        Current diagnosis of moderate aplastic anemia or unilineage bone marrow failure disorders.

          -  Moderate aplastic anemia is defined as aplastic anemia (hypocellular bone marrow for
             age) with no evidence for other disease processes causing marrow failure, and
             depression of at least two out of three blood counts below the normal values:

               -  ANC less than or equal to 1200/mm(3)

               -  platelet count less than or equal to 70,000/mm(3)

               -  anemia with hemoglobin less than or equal to 8.5 g/dL and absolute reticulocyte
                  count less than or equal to 60,000/mm(3) in transfusion-dependent patients but
                  not fulfilling the criteria for severe disease defined by depression of two of
                  the three peripheral counts:

               -  ANC less than or equal to 500/mm(3)

               -  platelet count less than or equal to 20,000/mm(3)

          -  reticulocyte count less than or equal to 60,000/mm(3)

          -  Unilineage bone marrow failure disorders are defined:

               -  Hemoglobin less than 8.5 g/dL and reticulocyte count less than 60,000 or red cell
                  transfusion dependent and hypocellular to normocellular bone marrow for age with
                  significantly reduced erythroid precursors.

               -  OR thrombocytopenia less than or equal to 30,000/uL or platelet transfusion
                  dependent and hypocellular to normocellular bone marrow for age with reduced
                  megakaryocytes.

          -  No evidence of viral or drug suppression of the marrow, dysplasia, or underproduction
             anemias secondary to B12, folate, iron or other reversible causes.

        Platelet transfusion dependent is defined as the need for platelet transfusion due to
        platelet counts of < 10,000/microL with no bleeding (prophylactic transfusion) or <
        20,000/microL with bleeding (therapeutic transfusion). Red cell transfusion dependent is
        defined as transfusion of greater than 4 units of blood in the 8 weeks prior to study
        entry.

        Age greater than or equal to 2 years old

        Weight greater than 12 kg

        EXCLUSION CRITERIA:

        Known diagnosis of Fanconi anemia

        Counts that meet criteria for severe aplastic anemia

        Infection not adequately responding to appropriate therapy

        HIV positivity

        Creatinine > 2.5 mg/dL

        Bilirubin > 2.0 mg/dL, including congenital abnormalities in the bilirubin count

        SGOT or SGPT >5 times the upper limit of normal

        Hypersensitivity to eltrombopag or its components

        Female subjects who are nursing or pregnant or are unwilling to take oral contraceptives or
        refrain from pregnancy if of childbearing potential

        Evidence of an active malignant hematological or clonal disorder, or abnormal cytogenetic
        studies of the bone marrow performed within 12 weeks of study entry.

        Unable to understand the investigational nature of the study or give informed consent or
        does not have a legally authorized representative or surrogate that can provide informed
        consent

        Moribund status or concurrent hepatic, renal, cardiac, neurologic, pulmonary, infectious,
        or metabolic disease of such severity that it would preclude the patient's ability to
        tolerate protocol therapy, or that death within 7-10 days is likely.

        Treatment with horse or rabbit ATG or Campath within 6 months of study entry.

        Treatment with cytokines such as G-CSF or Erythropoietin.

        Subjects with known cirrhosis in severity that would preclude tolerability of eltrombopag
        as evidenced by albumin less than 35g/L.

        Life expectancy of less than 3 months

        Patients with an active diagnosis of cancer who have received chemotherapeutic treatment or
        other specific antineoplastic drugs or radiation therapy within 6 months of study entry.

        Unable to take investigational drug