Trial of Volasertib With or Without Azacitidine in Patients With Myelodysplastic Syndromes

Inclusion criteria: * Patients 18 years and older with diagnosis of WHO classification-defined primary or treatment-related myeloid neoplasms classified as follows: * Refractory anaemia with excess blasts (RAEB)-1 (5%-9% marrow blasts) or * RAEB-2 (10%-19% marrow blasts or 5% - 19% peripheral blast) or * Chronic Myelomonocytic Leukaemia (CMML) (5%-19% blasts) with white blood cell (WBC) count \<13000/mm3 or * Acute Myeloid Leukaemia (AML) (20%-29% marrow blasts, i.e., RAEB-t according to French-American-British \[FAB\] classification) with WBC count \<10000/mm3 * Patients classified as intermediate, high or very high-risk according to Revised - International Prognostic Scoring System (IPSS-R) at the time of enrolment * Patients who have received a maximum of 24 cycles of frontline HMA treatment prior to enrolment. * Patients must have received a minimum prior dosing schedule of either: * Azacitidine 75 mg/m2 x 5 days per cycle or 50 mg/m2 x 7 days per cycle, or * Decitabine 20 mg/m2 x 5 days per cycle, or * SGI-110 60 mg/m2 x 5 days per cycle * Patients must meet either one of the following criteria: * Progressive disease (PD, according to 2006 International Working Group (IWG) criteria) at any time after initiation of the prior HMA treatment, or * Relapse after initial complete (CR) or partial remission (PR) or haematological improvement (HI) (according to 2006 IWG criteria); or * Failure to achieve complete or partial remission or HI (according to 2006 IWG) with no evidence of progression (i.e., Stable Disease \[SD\]) after at least six cycles of prior azacitidine treatment or at least four cycles of other prior HMA treatment. * Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 at screening * Signed written informed consent consistent with International Conference of Harmonization Good Clinical Practice (ICH-GCP) and local legislation Exclusion criteria: * Prior systemic therapy (including investigational drugs) for MDS, CMML or AML within 14 days before treatment with study medication. * Patients requiring intervention for white blood cell count control with hydroxyurea, chemotherapy, or leukapheresis. * Prior exposure to more than one line of HMA based treatment. * Prior exposure to volasertib or other polo-kinase inhibitors * Patients who were unable to tolerate prior HMA treatment * Patients with history of hematopoietic stem cell transplant (HSCT) * Known hypersensitivity to the trial drugs or its excipients * Second malignancy currently requiring active therapy (except for hormonal/anti-hormonal treatment, e.g., in prostate or breast cancer). * QTcF value \>470 ms or QT prolongation deemed clinically relevant by the investigator (e.g., congenital long QT syndrome).