Efficacy and Safety of Eltrombopag + CSA in Patients With Moderate Aplastic Anemia (EMAA)

Inclusion Criteria:

1. Current diagnosis of a Moderate Aplastic Anemia requiring standard treatment with CSAwithout prior specific therapy. MAA is defined as Aplastic Anemia fulfilling the following criteria:

• no evidence for other disease causing marrow failure

• hypocellular bone marrow for age

• depression of at least two out of three peripheral blood counts below the normalvalues:

• absolute neutrophil count (ANC) < 1.2 G/L and > 0.5 G/l

• platelet count < 70 G/L

• absolute reticulocyte count < 60 G/L without fulfilling the criteria for SAA (hypocellularity of bone marrow 25 % anddepression of two of the three peripheral counts: ANC < 0.5 G/L, platelet count < 20G/L, reticulocyte count < 20 G/L)

2. In this study need for treatment with CSA is defined as:

2a) transfusion-independent MAA and:

• ANC < 1.0 G/L

• or hemoglobin < 8.5 g/dl and reticulocyte count < 60 G/L

• or platelet count < 30 G/L

• or significant clinical symptoms (infections, bleeding, anemia)

2b) transfusion-dependent moderate aplastic anemia

• Platelet transfusion dependency is defined as prophylactic transfusion (plateletcounts < 10 G/L with no bleeding) or therapeutic transfusion in the 12 weeks prior tostudy entry

• Red cell transfusion dependency is defined as transfusion of at least 4 units ofpacked red blood cell concentrates (PRBC) in the 12 weeks prior to study entry

3. A signed and dated informed consent is necessary before the conduct of anystudy-specific procedure.

Exclusion Criteria:

1. Age < 18 years

2. Severe or Very Severe Aplastic Anemia (hypocellularity of bone marrow 25 % anddepression of two of the three peripheral counts: ANC < 0.5 G/L, platelet count < 20G/L, reticulocyte count < 20 G/L)

3. Constitutional aplastic anemia (Fanconi anemia or Dyskeratosis congenita)

4. Clonal myeloid disorders based on cytogenetic findings performed within 12 weeks ofstudy entry. Especially, patients with cytogenetic abnormalities which are recurrentin MDS are not eligible for the study.

5. Bone marrow reticulin fibrosis of grade 3 or greater

6. Severe concurrent diseases precluding the patient's ability to tolerate protocoltherapy

7. ALT > 3 times the upper limit of normal if this elevation is progressive, orpersistent for 4 weeks, or accompanied by increased direct bilirubin, or accompaniedby clinical symptoms of liver injury or evidence for hepatic decompensation

8. Infection not adequately responding to appropriate therapy

9. HIV-positivity (patients with Hepatitis B or Hepatits C-positivity are only incombination with hepatic failure (see criteria 7) excluded)

10. Moribund status with a likely death within 3 months

11. History of malignancy other than localized tumors diagnosed more than one yearpreviously and treated surgically with curative intent (for instance squamous cell orother skin cancers, stage 1, breast cancer in situ, cervical carcinoma in situ...).

12. Prior specific treatment of Aplastic Anemia with immunosuppression or androgens orinterleukin2-receptor-antibodies. The use of these drugs in context of other disordersbefore diagnosis of aplastic anemia is not an exclusion criteria if these treatmentswere finished longer than 6 months before study entry.

13. Treatment with other hematological effective drugs (including erythropoetin) within 3months before study entry as well as treatment with corticosteroids and G-CSF within 3weeks before enrollment

14. Known hypersensitivity to Eltrombopag or its components

15. Known hypersensitivity to Ciclosporin

16. Current nursing, pregnancy, or unwillingness to take oral contraceptives or use abarrier method of birth control to refrain from pregnancy as well as a missing orpositive pregnancy test within the last 14 days before inclusion for women withchildbearing potential during the course of this study.

17. Inability to understand the investigational nature of the study or to give informedconsent.

18. Renal failure with creatinine > 2× upper limit of normal.

19. Uncontrolled hypertension

20. Participation in any study using an investigational drug or treatment with aninvestigational drug within 30 days preceding the first dose of study medication