Volasertib in Combination With Azacitidine in Japanese Patients With Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02201329
Recruitment Status : Completed
First Posted : July 28, 2014
Last Update Posted : October 1, 2015
Information provided by (Responsible Party):
Boehringer Ingelheim

Brief 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.

Condition or disease Intervention/treatment Phase
Myelodysplastic Syndromes Leukemia, Myelomonocytic, Chronic Drug: Azacitidine Drug: Volasertib Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 5 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open Label Phase I Trial of Intravenous Volasertib in Combination With Subcutaneous Azacitidine in Japanese Patients With Higher-risk Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia
Study Start Date : August 2014
Actual Primary Completion Date : January 2015
Actual Study Completion Date : September 2015

Arm Intervention/treatment
Experimental: A
Volasertib escalating doses + azacitidine
Drug: Azacitidine
Azacitidine (subcutaneous)

Drug: Volasertib
Volasertib escalating doses (intravenous)

Primary Outcome Measures :
  1. Maximum tolerated dose (MTD) [ Time Frame: up to 57 days ]
  2. Dose limiting toxicities (DLT) [ Time Frame: up to 57 days ]

Secondary Outcome Measures :
  1. Overall objective Response (OR) [ Time Frame: 9 months ]
  2. Maximum measured plasma concentration (Cmax) [ Time Frame: up to 15 days ]
  3. Area under the plasma concentration-time curve over the time interval from zero extrapolated to infinity (AUC0-inf) [ Time Frame: up to 15 days ]

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Ages Eligible for Study:   20 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02201329

1230.35.001 Boehringer Ingelheim Investigational Site
Aichi, Nagoya, Japan
1230.35.005 Boehringer Ingelheim Investigational Site
Gunma, Maebashi, Japan
1230.35.002 Boehringer Ingelheim Investigational Site
Nagasaki, Nagasaki, Japan
1230.35.003 Boehringer Ingelheim Investigational Site
Tokyo, Sinagawa-ku, Japan
Sponsors and Collaborators
Boehringer Ingelheim
Study Chair: Boehringer Ingelheim Boehringer Ingelheim

Responsible Party: Boehringer Ingelheim Identifier: NCT02201329     History of Changes
Other Study ID Numbers: 1230.35
First Posted: July 28, 2014    Key Record Dates
Last Update Posted: October 1, 2015
Last Verified: September 2015

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Pathologic Processes
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Leukemia, Myeloid
Myelodysplastic-Myeloproliferative Diseases
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors