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

• Status: Recruiting
• Trial end date: 2023-09-30
• Target enrollment: 0
• Participant gender: All

Summary

The aim of this study is to improve treatment of Moderate Aplastic Anemia (MAA) by evaluating the safety and efficiency of Eltrombopag as a new treatment option in patients with therapy requiring MAA.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: B. Höchsmann
• Treatments: Cyclosporine; Cyclosporins

Criteria

Inclusion Criteria:

1. Current diagnosis of a Moderate Aplastic Anemia requiring standard treatment with CSA without 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 normal values:

• 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 % and depression of two of the three peripheral counts: ANC < 0.5 G/L, platelet count < 20 G/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 (platelet counts < 10 G/L with no bleeding) or therapeutic transfusion in the 12 weeks prior to study entry

• Red cell transfusion dependency is defined as transfusion of at least 4 units of packed 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 any study-specific procedure.

Exclusion Criteria:

1. Age < 18 years

2. Severe or Very Severe Aplastic Anemia (hypocellularity of bone marrow 25 % and depression of two of the three peripheral counts: ANC < 0.5 G/L, platelet count < 20 G/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 of study entry. Especially, patients with cytogenetic abnormalities which are recurrent in 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 protocol therapy

7. ALT > 3 times the upper limit of normal if this elevation is progressive, or persistent for 4 weeks, or accompanied by increased direct bilirubin, or accompanied by 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 in combination 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 year previously and treated surgically with curative intent (for instance squamous cell or other skin cancers, stage 1, breast cancer in situ, cervical carcinoma in situ...).

12. Prior specific treatment of Aplastic Anemia with immunosuppression or androgens or interleukin2-receptor-antibodies. The use of these drugs in context of other disorders before diagnosis of aplastic anemia is not an exclusion criteria if these treatments were finished longer than 6 months before study entry.

13. Treatment with other hematological effective drugs (including erythropoetin) within 3 months before study entry as well as treatment with corticosteroids and G-CSF within 3 weeks 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 a barrier method of birth control to refrain from pregnancy as well as a missing or positive pregnancy test within the last 14 days before inclusion for women with childbearing potential during the course of this study.

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

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 an investigational drug within 30 days preceding the first dose of study medication