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).