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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Efficacy and Safety of Thrombopoetin-Receptor Agonist Eltrombopag in in Combination With Ciclosporin A in Moderate Aplastic Anemia (EMAA): Prospective Randomized Multicent

Brief 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.

Detailed Summary:

After enrollment (see detailed inclusion and exclusion criteria below) the patients are randomized either to the Placebo or Eltrombopag arm. The randomization is double blinded. Randomization will take in account patient's age and disease severity by stratifying into 4 block combinations to ensure homogeneity between treatment arms. All patients receive background therapy with CSA, regardless of randomisation group, to treat MAA according to current standard of care.

Eltrombopag (or Placebo) is given at a daily starting dose of 150 mg orally as 75 mg tablets once daily (2 tablets Eltrombopag or placebo per day), (Olnes et al NEJM 2012).

In Asian patients Eltrombopag (or Placebo) is given at a daily starting dose of 75 mg orally (1 tablet Eltrombopag or placebo per day). In Asian-Caucasian patients no dose reduction of the starting dose is carried out, but cautious observation of the liver function due to the possibility of altered Eltrombopag metabolism is recommended.

Dose reduction:

In patients without history of thromboembolism or known risk factors for thrombembolism dose reduction (the possibility of an alternating dose schedule is given) is recommended if the platelet count is increasing > 150 G/L.

• Dosage should be decreased to achieve a platelet count between 100 and 150 G/L after reaching a sufficient erythrocyte and granulocyte response (see 10.1).
• If the platelet count decreases below 100 G/L the Eltrombopag dose should be escalated again.
• Eltrombopag should be discontinued if the platelet count exceeds 450 G/L and could be restarted with a lower dose after decre
  Sponsor: B. Höchsmann
  

  Current Primary Outcome: Trilineage hematologic response rate (CR + PR) [ Time Frame: 6 months after treatment start ]

  The primary objective of this trial is to investigate whether Eltrombopag added to standard immunosuppressive treatment increases the rate of hematologic responses (complete and partial response) in untreated AA patient at six months after treatment start.

  A complete response (according to Marsh et al Blood 1992):

  A peripheral blood count with an ANC > 2.0 G/L and a platelet count > 100 G/L and transfusion independence.

  A partial response (according to Marsh et al Blood 1992):

  A peripheral blood count with an ANC >1.0 G/L and a platelet count >30 G/L and transfusion independence Transfusion independence is defined as No need for platelet transfusions in the last 4 weeks prior to evaluation and no need for packed red blood cell concentrates (PRBC) in the last 6 weeks prior to evaluation.

  Patients who remain transfusion-dependent will be classified as non-responders regardless of the ANC and platelet count.

  
  
  

  Original Primary Outcome: Same as current
  
  

  Current Secondary Outcome:

  • Trilineage hematological response rate (CR and PR, detailed definition => primary endpoint) at 3, 12 and 18 [ Time Frame: 3, 12 and 18 months ]
    Increase of the platelet count by 20 G/L or hemoglobin by > 1.5 g/dL above baseline in patients without prior transfusion dependence or an absolute increase in ANC of > 0.5 G/L respectively at least a 100 percent increase over the baseline ANC in those with pre-treatment absolute ANC of ≤ 0.5 G/L or transfusion independence for a minimum of 8 weeks or a reduction of transfused units during the last 8 weeks compared with the 8 weeks previous to study entry in patients with prior transfusion dependency
  • single hematological response rate (CR and PR, detailed definition => primary endpoint) at 3, 12 and 18 [ Time Frame: 3, 12 and 18 months ]
    Increase of the platelet count by 20 G/L or hemoglobin by > 1.5 g/dL above baseline in patients without prior transfusion dependence or an absolute increase in ANC of > 0.5 G/L respectively at least a 100 percent increase over the baseline ANC in those with pre-treatment absolute ANC of ≤ 0.5 G/L
  • cumulative incidence of response [ Time Frame: 3, 6, 12 and 18 months ]
    proportion of patients with need for transfusions and number of units transfused (PRBC and platelet concentrates) since start of treatment cumulative incidence of progress to SAA/VSAA or intensive immunosuppressive treatment with ATG
  • Comparison of number of SAEs between the two arms (CSA + Placebo versus CSA + Eltrombopag [ Time Frame: 2 years ]
    using the CTCAE criteria and the study specific criteria (developing of a ALT > 3.0 × ULN combined with an elevation of bilirubine > 2.0 × ULN, thrombotic/thromboembolic complications, clonal evolution)
  
  
  

  Original Secondary Outcome: Same as current
  
  Information By: University of Ulm
  

  Dates:
  Date Received: February 29, 2016
  Date Started: March 2015
  Date Completion: September 2021
  Last Updated: May 11, 2016
  Last Verified: February 2016