Volasertib in Combination With Low-dose Cytarabine in Patients Aged 65 Years and Above With Previously Untreated Acute Myeloid Leukaemia, Who Are Ineligible for Intensive Remission Induction Therapy (POLO-AML-2)
Condition: Leukemia, Myeloid, Acute
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Intervention: Placebo; Volasertib; Cytarabine
Intervention description: Placebo matching Volasertib; Volasertib; Cytarabine
Intervention MeSH terms: Cytarabine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Enrollment: 666.0
Sex: All
Minimum age: 65 Years
Healthy volunteers: No

Summary:

      To investigate the efficacy, safety, and pharmacokinetics of intravenous volasertib +
      subcutaneous low dose cytarabine in patients >= 65 years of age with previously untreated
      acute myeloid leukaemia, ineligible for intensive remission induction therapy
    

Eligibility criteria:

        Inclusion criteria:

          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)
             is allowed.

          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.

        Exclusion criteria:

          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
             M3).

          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.