Volasertib + Decitabine in Patients With Acute Myeloid Leukemia (AML)
Condition: Leukemia, Myeloid, Acute
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Intervention: decitabine iv; volasertib iv infusion
Intervention description: decitabine iv fixed dose; volasertib iv infusion (Body Surface Area (BSA) based dosing)
Intervention MeSH terms: Decitabine
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 13.0
Sex: All
Minimum age: 65 Years
Healthy volunteers: No

Summary:

      Dose Escalation (MTD Finding) Phase: To investigate the maximum tolerated dose (MTD), safety
      and pharmacokinetics of different volasertib administration schedules in combination with
      decitabine in previously untreated AML patients >= 65 years of age who are considered
      ineligible for standard intensive therapy, or patients with relapsed or refractory AML
      regardless of prior treatment status.

      MTD Extension Phase: To collect additional data on safety, efficacy and pharmacokinetics of
      volasertib in combination with decitabine in previously untreated patients with AML >= 65
      years of age and considered ineligible for standard intensive therapy.
    

Eligibility criteria:

        Inclusion criteria:

          1. Dose Escalation Phase: patients with previously untreated AML, relapsed or refractory
             AML regardless of prior treatment status.

          2. MTD Extension Phase: previously untreated AML (prior treatment for Myelodysplastic
             Syndrome(MDS) is allowed).

          3. Age >= 65 years.

          4. Previously untreated patients must be ineligible for receiving standard intensive
             therapy at the time of enrolment, in the opinion of the investigator and based on
             documented medical reasons.

          5. Histologically or cytologically confirmed AML (except for APL, FAB
             (French-American-British)subtype M3) according to the World Health Organisation
             classification.

          6. Eastern co-operative oncology group (ECOG) performance score =< 1 at screening.

          7. Signed and dated written informed consent by start date of Screening Visit in
             accordance with Good Clinical Practice and local legislation.

        Exclusion criteria:

          1. MTD Extension Phase: Prior chemotherapy for AML (except for hydroxyurea). Patients can
             receive treatment with hydroxyurea in order to reduce high White Blood Cells count for
             no more than 28 days (cumulative); discontinuation of hydroxyurea at least one day
             prior to the study treatment is required. Please note that any prior therapy for MDS
             is allowed.

          2. Acute promyelocytic leukemia (APL, FAB subtype M3), according to World Health
             Organisation classification.

          3. Hypersensitivity to the trial drugs.

          4. Other malignancy currently requiring active therapy (except for hormonal/anti-hormonal
             treatment, e.g. in prostate or breast cancer).

          5. Known clinical central nervous system (CNS) symptoms deemed by the investigator to be
             related to leukemic CNS involvement.

          6. QTcF (QT interval corrected for heart rate by the Fridericia formula) > 470 ms,
             calculated as the mean value of the triplicates taken at least 2 minutes apart at
             baseline or QTcF prolongation deemed clinically relevant by the investigator.

          7. Baseline Left Ventricular Ejection Fraction of < 45% or below the lower limit of
             institutional normal range.

          8. Aspartate amino transferase (AST) or alanine amino transferase (ALT) > 2.5 x the upper
             limit of normal (ULN). Patients with elevated liver enzyme(s) due to leukemic
             involvement are allowed up to = 5 x the ULN.

          9. Total bilirubin > 1.5 x ULN. For patients with Gilbert's syndrome or elevation due to
             hepatic infiltrate, total bilirubin must be <4 x ULN.

         10. Creatinine clearance (CLcr) < 30 ml/min (estimated creatinine clearance by the
             Cockcroft-Gault (C-G) equation.

         11. Severe illness or organ dysfunction involving the kidneys, liver or other organ
             system, including active uncontrolled infection, which in the opinion of the
             investigator precludes treatment with decitabine or would interfere with the
             evaluation of the safety of the study treatment.

         12. Presence of clinically relevant cardiovascular abnormalities such as uncontrolled
             hypertension, congestive heart failure New York Heart Association (NYHA)
             Classification of 3, unstable angina or poorly controlled arrhythmia as determined by
             the investigator. Myocardial infarction within 6 months prior to study entry.

         13. Significant concurrent psychiatric disorder or social situation that according to the
             investigator's judgment would compromise patient's safety or compliance, interfere
             with consent, study participation, or interpretation of study results.

         14. Patients with a systemic fungal, bacterial, viral, or other infection that is not
             controlled.

         15. Contraindications for decitabine treatment according to the manufacturer's prescribing
             information provided in the Investigator Site File

         16. Female patients of childbearing potential who are sexually active and unwilling to use
             a medically acceptable method of contraception during the trial and for a minimum of 6
             months after completion of study treatment.

         17. 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 completion of study treatment.

         18. Pregnant or breast feeding patients.

         19. Treatment with any investigational drug within 2 weeks of administration of first
             study medication dose or within less than five half -lives of the investigational drug
             before treatment with the present trial drug, whichever is shorter, and / or
             persistence of toxicities of prior anti-leukemic therapies which are deemed clinically
             relevant.

         20. Prior treatment with a Plk inhibitor such as volasertib or treatment in a clinical
             trial using a Plk inhibitory compound.