Clinical Trials

Inclusion criteria:

• Phase I Dose Escalation only: patients with previously untreated AML, relapsed or refractory AML regardless of prior treatment status. In addition, patients with high risk MDS, as defined as 10% or more blasts identified in bone marrow are eligible
• Phase I MTD Extension and Phase IIa only: previously untreated AML
• Age ≥ 65 years
• Previously untreated patients must be ineligible for receiving standard intensive therapy based on documented medical reasons
• Histologically or cytologically confirmed AML (except for APL, FAB subtype M3) or MDS (for phase I patients only), according to the WHO classification
• Patients must be eligible for treatment with decitabine
• Eastern co-operative oncology group (ECOG) performance score ≤ 2 at screening
• Signed and dated written informed consent by start date of Screening Visit in accordance with GCP and local legislation

Exclusion criteria:

• Phase I MTD Extension and Phase IIa only: Prior chemotherapy for AML. Patients who receive treatment with hydroxyurea in order to reduce high WBC count for no more than 28 days (cumulative) require discontinuation of hydroxyurea at least one day prior to the study treatment. Please note that any prior therapy for MDS is allowed
• Acute promyelocytic leukemia (APL, FAB subtype M3), according to WHO classification.
• Hypersensitivity to the trial drugs
• Second malignancy currently requiring active therapy (except for hormonal/anti-hormonal treatment, e.g. in prostate or breast cancer).
• Current clinical central nervous system (CNS) symptoms deemed by the investigator to be related to leukemic CNS involvement (no lumbar puncture required, clinical assessment per investigator's judgment is sufficient)
• QTcF > 470 ms, calculated as the mean value of the triplicates taken at least 2 minutes apart at baseline or QTcF prolongation deemed clinically relevant by the investigator.
• Baseline LVEF of < 45% or below the lower limit of institutional normal range
• Aspartate amino transferase (AST) or alanine amino transferase (ALT) > 2.5 x the upper limit of normal (ULN). Patients with elevated liver enzyme(s) due to leukemic involvement are allowed up to ≤ 5 x the ULN.
• Total bilirubin > 1.5 x ULN. For patients with Gilbert's syndrome or elevation due to hepatic infiltrate, total bilirubin must be <4 x ULN.
• Creatinine clearance (CLcr) < 30 ml/min (estimated creatinine clearance by the Cockcroft-Gault (C-G) equation.
• Severe illness or organ dysfunction involving the kidneys, liver or other organ system, including active uncontrolled infection, which in the opinion of the investigator precludes treatment with decitabine or would interfere with the evaluation of the safety of the study treatment.
• Presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure New York Heart Association (NYHA) Classification of 3, unstable angina or poorly controlled arrhythmia as determined by the investigator. Myocardial infarction within 6 months prior to study entry.
• Significant concurrent psychiatric disorder or social situation that according to the investigator's judgment would compromise patient's safety or compliance, interfere with consent, study participation, or interpretation of study results.
• Patients with a systemic fungal, bacterial, viral, or other infection that is not controlled
• Contraindications for decitabine treatment according to the manufacturer's prescribing information provided in the ISF.
• Female patients of childbearing potential who are sexually active and unwilling to use a medically acceptable method of contraception during the trial and for a minimum of 6 months after completion of study treatment.
• Male patients with partners of childbearing potential who are unwilling to use condoms in combination with a second medically acceptable method of contraception during the trial and for a minimum of 6 months after completion of study treatment.
• Pregnant or breast feeding patients.
• Treatment with any investigational drug within 2 weeks of administration of first study medication dose or within less than five half times of the investigational drug before treatment with the present trial drug, whichever is shorter, and / or persistence of toxicities of prior anti-leukemic therapies which are deemed clinically relevant.
• Prior treatment with a PLK inhibitor such as volasertib or treatment in a clinical trial using a PLK inhibitory compound.
• Prior treatment with decitabine