Tolerability and Efficacy of Midostaurin to 10-day Decitabine in Unfit Adult AML and High Risk MDS Patients

Inclusion Criteria:

* Patients with:

  * a diagnosis of AML and related precursor neoplasms according to WHO 2016 classification (excluding acute promyelocytic leukemia) including secondary AML (after an antecedent hematological disease (e.g. MDS) and therapy-related AML, or
  * a diagnosis of myelodysplastic syndrome with excess of blasts (MDS) and International Prognostic Score System (IPSS) \> 4.5
* Patients 18 years and older.
* Patients NOT eligible for standard chemotherapy, defined as hematopoietic cell transplantation comorbidity index (HCT-CI) ≥ 3.

or Patients NOT eligible for standard chemotherapy for other reasons (wish of patient).

* White blood cell (WBC) ≤ 30 x109/L (prior hydroxyurea allowed for a maximum of 5 days, stop 2 days before start decitabine treatment)
* Adequate renal and hepatic functions unless clearly disease related as indicated by the following laboratory values:

  * Serum creatinine ≤ 221.7 µmol/L (≤ 2.5 mg/dL ), unless considered AML-related
  * Serum bilirubin ≤ 2.5 x upper limit of normal (ULN), unless considered AML-related or due to Gilbert's syndrome
  * Alanine transaminase (ALT) ≤ 2.5 x ULN, unless considered AML-related
* WHO performance status 0, 1 or 2.
* Patient is willing and able to use adequate contraception during and until 5 months after the last protocol treatment.
* Written informed consent.
* Patient is capable of giving informed consent.

Exclusion Criteria:

* Acute promyelocytic leukemia.
* Acute leukemia's of ambiguous lineage according to WHO 2016
* Patient has symptomatic central nervous system (CNS) leukemia (NO routinely lumbar puncture required to investigate CNS involvement)
* Blast crisis of chronic myeloid leukemia.
* Diagnosis of any previous or concomitant malignancy is an exclusion criterion:
* except when the patient completed successfully treatment (chemotherapy and/or surgery and/or radiotherapy) with curative intent for this malignancy at least 6 months prior to randomization. OR
* except for basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix
* Patients previously treated for AML (any antileukemic therapy including investigational agents), a short treatment period ( ≤ 5 days) with Hydroxyurea is allowed
* Current concomitant chemotherapy, radiation therapy, or immunotherapy; other than hydroxyurea
* Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, pulmonary disease etc.)
* Cardiac dysfunction as defined by:

  * Myocardial infarction within the last 3 months of study entry, or
  * Reduced left ventricular function with an ejection fraction \< 40% as measured by MUGA scan or echocardiogram or
  * Unstable angina or
  * New York Heart Association grade IV congestive heart failure or
  * Unstable cardiac arrhythmias.
* History of stroke or intracranial hemorrhage within 6 months prior to randomization.
* Patient has a history of human immunodeficiency virus or active infection with Hepatitis C or B.
* Patients known to be pregnant
* Patients with a history of non-compliance to medical regimens or who are considered unreliable with respect to compliance.
* Patients with any serious concomitant medical condition which could, in the opinion of the investigator, compromise participation in the study.
* Patients who have senile dementia, mental impairment or any other psychiatric disorder that prohibits the patient from understanding and giving informed consent.
* Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule