Volasertib in Combination With Azacitidine in Japanese Patients With Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia
Condition: Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic
MeSH terms: Leukemia; Preleukemia; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Myelodysplastic Syndromes; Syndrome
Intervention: Azacitidine; Volasertib
Intervention description: Azacitidine (subcutaneous); Volasertib escalating doses (intravenous)
Intervention MeSH terms: Azacitidine
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 5.0
Sex: All
Minimum age: 20 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      To identify the maximum tolerated dose or recommended dose for further development of
      volasertib in combination with azacitidine in Japanese patients with myelodysplastic
      syndromes or chronic myelomonocytic leukemia, and evaluate the safety and tolerability,
      pharmacokinetics and the preliminary efficacy of this combination.
    

Eligibility criteria:

        Inclusion criteria:

          1. Patients of age >=20 and <=80 years

          2. Patients with primary or treatment-related myelodysplastic syndrome (MDS) or chronic
             myelomonocytic leukemia (CMML), who are not eligible for hematopoietic stem cell
             transplantation based on the investigator's judgment, that meet one of the following
             criteria:

               -  Intermediate-2 and high-risk MDS according to the International Prognostic
                  Scoring System, in the setting of 5-30% bone marrow blasts

               -  CMML with >= 10% marrow blasts without myeloproliferative disorder (white blood
                  cell count of <13,000/ µL)

          3. Patients with no prior azacitidine treatment, or with prior azacitidine treatment that
             meet one of the following criteria:

               -  Patients failing to achieve haematological improvement, partial remission, marrow
                  complete remission or complete remission after 3 cycles of azacitidine or
                  progressed at any time after start of azacitidine

               -  Patients achieved an initial response and subsequently develop disease
                  progression or relapse

          4. Eastern Cooperative Oncology Group performance status score 0 or 1 at screening

          5. Signed written informed consent consistent with Good Clinical Practice.

        Exclusion criteria:

          1. Treatment with systemic therapy for MDS, including an investigational drug, within 14
             days before the first dose of study treatment, except for lenalidomide within 12 weeks
             before the first dose of study treatment, or lack of recovery from any acute
             toxicities pertinent to the prior systemic therapy.

          2. Prior treatment with volasertib

          3. Contraindications for azacitidine treatment according to the manufacturer's product
             information

          4. Known hypersensitivity to the trial drugs or its excipients

          5. Concomitant malignancy currently requiring active therapy (except for
             hormonal/anti-hormonal treatment, e.g. in prostate or breast cancer)

          6. QTcF prolongation >470 ms or QT prolongation deemed clinically relevant by the
             investigator (e.g., congenital long QT syndrome).

          7. Total bilirubin >1.5 x upper limit of normal (ULN) not related to Gilbert's syndrome,
             hemolysis, or secondary to MDS at screening

          8. Aspartate amino transferase or alanine amino transferase >2.5 x ULN

          9. Serum creatinine >1.5 x ULN at screening

         10. Arterial oxygen pressure <60 torr or arterial oxygen saturation <92% (at room air)

         11. Active hepatitis B or hepatitis C, or laboratory evidence of hepatitis with positive
             results of hepatitis B surface antigen and/or hepatitis C antibody.

         12. Human immunodeficiency virus infection.

         13. Severe illness or organ dysfunction involving the heart, lung, kidney, liver or other
             organ system, which in the opinion of the investigator would interfere with the
             evaluation of the safety of the study treatment including; infection requiring active
             treatment, poorly controlled ventricular/atrial tachyarrhythmia, use of heart pacer,
             unstable angina pectoris, history of myocardial infarction or severe congestive heart
             failure, clinically unstable cardiac or pulmonary disease

         14. Any 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

         15. All male patients and female patients of child bearing potential who are unwilling to
             use a medically acceptable method of contraception during the trial and at least 6
             months after the end of study treatment (i.e. hormonal contraception, intrauterine
             device, condom with spermicide, etc.). Note: females are considered to be of child
             bearing potential unless they have been surgically sterilized or are post-menopausal
             (complete absence of menses for at least 12 months without other medical reasons).

         16. Pregnant or nursing female patients

         17. Known or suspected active alcohol or drug abuse