AML patients displaying t(8;21) have a relatively favourable outcome. Nevertheless, only
      approximately 50% of patients carrying this cytogenetic aberration are alive at 5 years. This
      suggests that some patients have more aggressive leukemic phenotypes and indicates the need
      for treatment optimization with novel therapies.

      The mutated KIT gene as well as the FLT3-ITD mutation have recently been identified as
      factors most likely to explain the heterogeneous clinical outcomes within the group of
      t(8;21) AML. The FLT3 and c-KIT genes encode type III receptor tyrosine kinases (RTK) with
      important and partly redundant functions in early hematopoietic stem cells. Various
      activating mutations have been described for both genes. For c-KIT, the incidence ranges from
      17 to 48% depending on the source population and type of mutations determined. It has been
      consistently shown that in AMLs with t(8;21), mutated c-KIT is associated with a dramatically
      increased risk of relapse and reduced overall survival compared to their unmutated
      counterparts. The FLT3-ITD mutation has a similar negative effect on prognosis in the patient
      group of t(8;21) mutated AMLs as c-KIT.

      PKC412 (midostaurin) is known to inhibit the c-KIT RTK activity as well as the FLT3 kinase,
      both in patients with ITD and TKD mutations. It should therefore be possible to abrogate the
      negative impact of pathologically increased c-KIT or FLT3-ITD activity on relapse and overall
      survival by using midostaurin in this patient population. Aim of the proposed clinical trial
      is to prove the efficacy of midostaurin in c-KIT or FLT3-ITD mutated t(8;21)- AMLs in an
      open-label one-arm design.