A Phase III Randomised, Double-blind, Controlled, Parallel Group Study of Intravenous Volasertib in Combination With Subcutaneous Low-dose Cytarabine vs. Placebo + Low-dose Cytarabine in Patients >=65 Years With Previously Untreated Acute Myeloid Leukaemia, Who Are Ineligible for Intensive Remission Induction Therapy
1. Age >= 65years.
2. Cytologically/histologically confirmed acute myeloid leukaemia (AML) according to WHO
classification; (except for acute promyelocytic leukaemia (APL).
3. Previously untreated AML (except for hydroxyurea and/or corticosteroid therapy for no
more than 28 days (cumulative)). Previous therapy for Myelodysplastic Syndrome (MDS)
4. Investigator considers patient ineligible for intensive remission induction therapy
based on documented medical reasons (e.g. disease characteristics like AML genetics,
type of AML (de novo or secondary), and patient characteristics like performance
score, concomitant diagnoses, organ dysfunctions).
5. Patient is eligible for Low-Dose Cytarabine (LDAC) treatment.
6. Eastern co-operative oncology group (ECOG) performance score <= 2 at screening.
7. Signed and dated written informed consent by start date of Screening visit in
accordance with Good Clinical Practice (GCP) and local legislation.
1. Prior or concomitant chemotherapy for AML (with the exception of hydroxyurea and/or
corticosteroid therapy for no more than 28 days (cumulative)). Please note that any
prior therapy for MDS is allowed.
2. Treatment with any investigational drug within 2 weeks before first administration of
present trial drug.
3. Acute promyelocytic leukaemia (French-American-British (FAB) classification subtype
4. Current clinical central nervous system (CNS) symptoms deemed by the investigator to
be related to leukaemic CNS involvement (no lumbar puncture required, clinical
assessment per investigator´s judgement is sufficient).
5. Hypersensitivity to one of the trial drugs or the excipients.
6. Severe illness or organ dysfunction involving the heart, kidney, liver or other organ
system (e.g. active infection, clinically relevant impairment of cardiac function,
severe heart failure/cardiac insufficiency, unstable angina pectoris or history of
recent myocardial infarction), which in the opinion of the investigator precludes
treatment with LDAC.
7. Corrected QT interval according to Fridericia (QTcF) prolongation > 470 ms or QT
prolongation deemed clinically relevant by the investigator (e.g., congenital long QT
syndrome).The QTcF will be calculated as the mean of the 3 Electrocardiogram (ECGs)
taken at screening.
8. Total bilirubin > 3 x upper limit of normal (ULN).
9. Creatinine clearance (CLcr) < 30 ml/min (estimated creatinine clearance by the
Cockcroft-Gault (C-G) equation) .
10. Active hepatitis B or hepatitis C, or laboratory evidence for a chronic infection.
11. HIV infection.
12. Second malignancy currently requiring active therapy (except for
hormonal/anti-hormonal treatment e.g. in prostate or breast cancer).
13. Any significant concurrent psychiatric disorder or social situation that according to
the investigator´s judgement would compromise patient´s safety or compliance,
interfere with consent, study participation, or interpretation of study results.
14. Known or suspected active alcohol or drug abuse.
15. Patient unable to comply with the protocol, in the opinion of the investigator.
16. 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 study treatment.