Phase I Dose Escalation Trial of Volasertib in Combination With Azacitidine in Patients With MDS or CMML
Condition: Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic
MeSH terms: Leukemia; Preleukemia; Leukemia, Myelomonocytic, Chronic; Myelodysplastic Syndromes; Syndrome
Intervention: Azacitidine; Volasertib
Intervention MeSH terms: Azacitidine
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      To investigate the maximum tolerated dose (MTD), safety, pharmacokinetics, and efficacy of
      volasertib in combination with azacitidine in patients with myelodysplastic syndromes (MDS)
      or chronic myelomonocytic leukemia (CMML) and not candidates for hematopoietic stem cell
      transplant
    

Eligibility criteria:

        Inclusion criteria:

          -  Adult patients with previously untreated, intermediate-2 or high- risk MDS or CMML not
             eligible for hematopoietic stem cell transplantation (HSCT) based on documented
             patients characteristics like age, performance status, concomitant diagnoses, and
             organ dysfunctions

          -  Further inclusion criteria apply

        Exclusion criteria:

          -  Prior or concomitant therapy for higher risk MDS (for example, but not limited to,
             hypomethylating agents like azacitidine). Note: Prior treatment with erythropoetin
             (EPO) is allowed up to > 1 week before treatment with study medication. Patients must
             have not received MDS therapy since diagnosis of higher-risk MDS. However, previous
             lenalidomide treatment could have been administered for lower-risk MDS treatment as
             long as this therapy was discontinued at least > 4 weeks before initiation of the
             current study treatment.

          -  Treatment with any investigational drug within 2 weeks before first administration of
             present trial drug or within less than 5 half lives of the investigational drug before
             treatment with the present trial drug, whichever is longer.

          -  Second malignancy currently requiring active therapy (except for
             hormonal/anti-hormonal treatment, e.g. in prostate or breast cancer).

          -  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 Electrocardiograms (ECGs)
             taken at screening.

          -  Total bilirubin > 1.5 x upper limit of normal not related to Gilberts disease,
             hemolysis, or secondary to MDS.

          -  Aspartate amino transferase (AST) or alanine amino transferase (ALT) > 2.5 x the upper
             limit of normal (ULN) Creatinine > 1.5 x ULN

          -  Active hepatitis B or hepatitis C, or laboratory evidence for a chronic infection
             (hepatitis test results done in routine diagnostics are acceptable if done within 14
             days before first study treatment dose).

          -  HIV infection (HIV test results in routine diagnostics are acceptable if done within
             14 days before first study treatment dose).

          -  Severe illness or organ dysfunction involving the kidney, liver or other organ system
             (e.g. active uncontrolled infection , unstable angina pectoris or history of severe
             congestive heart failure, clinically unstable cardiac disease or pulmonary disease),
             which in the opinion of the investigator would interfere with the evaluation of the
             safety of the study treatment

          -  Further exclusion criteria apply