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).