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Phase I Dose Escalation Trial of Volasertib in Combination With Azacitidine in Patients With MDS or CMML

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: NCT01957644
Recruitment Status : Terminated
First Posted : October 8, 2013
Results First Posted : February 8, 2019
Last Update Posted : February 8, 2019
Information provided by (Responsible Party):
Boehringer Ingelheim

Brief 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

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open Label Phase I Dose Escalation Trial to Investigate the Maximum Tolerated Dose, Safety, Pharmacokinetics and Efficacy of Intravenous Volasertib in Combination With Subcutaneous Azacitidine in Patients With Previously Untreated High-risk Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML) and Not Candidates for Haematopoetic Stem Cell Transplant
Actual Study Start Date : November 6, 2013
Actual Primary Completion Date : December 16, 2016
Actual Study Completion Date : December 16, 2016

Arm Intervention/treatment
Experimental: Schedule A
Volasertib (d1 - one hour iv.) + Azacitidine 75 mg/m2 once daily on Days 1-7 (7 consecutive days) (28-day cycle)
Drug: Azacitidine
Drug: Volasertib
Experimental: Schedule B
Volasertib (d 7 - one hour iv.) + Azacitidine 75 mg/m2 once daily on Days 1-7 (7 consecutive days) (28-day cycle)
Drug: Azacitidine
Drug: Volasertib
Experimental: Schedule C
Volasertib (d 1 and 7 - one hour iv.) + Azacitidine 75 mg/m2 once daily on Days 1-7 (7 consecutive days) (28-day cycle)
Drug: Azacitidine
Drug: Volasertib

Primary Outcome Measures :
  1. Determination of the Maximum Tolerated Dose (MTD) Based on the Occurrence of Dose-limiting Toxicity (DLT) in Cycle 1 [ Time Frame: 4 weeks ]

    The primary objective of the dose-escalation part of this study was to determine the MTD of volasertib in combination with azacitidine. The MTD was to be identified based on the DLT information collected during the first treatment cycle of each dosing schedule. DLT was defined as a non-haematological drug-related toxicity of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥3. The MTD corresponded to the highest dose of volasertib and azacitidine at which the incidence of DLT was ≤17% (i.e. 1/6 patients) during Cycle 1.

    The planned dose escalation schedules of Part 2 were not completed because the trial was prematurely discontinued. Hence, a final conclusion of the MTD of volasertib in combination with azacitidine cannot be drawn in this trial.

    Number of patients with DLT in cycle 1 in escalation part is presented to determine MTD.

  2. Number of Participants With Dose Limiting Toxicities (DLT) in Cycle 1 [ Time Frame: 4 weeks ]
    Number of participants with Dose Limiting Toxicities (DLT) in Cycle 1 (escalation part to determine MTD) is presented .

Secondary Outcome Measures :
  1. Percentage of Patients With Objective Response (OR) [ Time Frame: From randomisation until data cut-off (16Dec2016); up to 159 weeks ]

    OR was defined as best overall response of complete remission (CR) or partial remission (PR) defined according to the International Working Group (IWG) 2006 criteria.

    Complete remission (CR):

    • Bone marrow: <5 % myeloblasts with normal maturation of all cell lines*
    • Persistent dysplasia will be noted*
    • Peripheral blood:
    • hemoglobin (Hgb) > 11 Grams Per Decilitre (g/dL)
    • Platelets >100 x 109/L
    • Neutrophils > 1.0 x 109/L
    • Blasts 0 % *Dysplastic changes should consider the normal range of dysplastic changes

    Partial remission (PR):

    All CR criteria if abnormal before treatment except:

    • Bone marrow blasts decreased by >50% to pre-treatment but still >5%
    • Cellularity and morphology not relevant

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

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): NCT01957644

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1230.33.33002 Boehringer Ingelheim Investigational Site
Marseille, France
1230.33.33001 Boehringer Ingelheim Investigational Site
Paris, France
1230.33.49011 Boehringer Ingelheim Investigational Site
Berlin, Germany
1230.33.49002 Boehringer Ingelheim Investigational Site
Dresden, Germany
1230.33.49001 Boehringer Ingelheim Investigational Site
Düsseldorf, Germany
1230.33.49005 Boehringer Ingelheim Investigational Site
Frankfurt/Main, Germany
1230.33.49004 Boehringer Ingelheim Investigational Site
Freiburg, Germany
1230.33.49010 Boehringer Ingelheim Investigational Site
Hamburg, Germany
1230.33.49008 Boehringer Ingelheim Investigational Site
Hannover, Germany
1230.33.49012 Boehringer Ingelheim Investigational Site
Kassel, Germany
1230.33.49014 Boehringer Ingelheim Investigational Site
Leipzig, Germany
1230.33.49009 Boehringer Ingelheim Investigational Site
Mannheim, Germany
1230.33.49006 Boehringer Ingelheim Investigational Site
München, Germany
1230.33.49003 Boehringer Ingelheim Investigational Site
Ulm, Germany
Sponsors and Collaborators
Boehringer Ingelheim
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Study Chair: Boehringer Ingelheim Boehringer Ingelheim
Additional Information:
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Responsible Party: Boehringer Ingelheim Identifier: NCT01957644    
Other Study ID Numbers: 1230.33
2013-001290-24 ( EudraCT Number: EudraCT )
First Posted: October 8, 2013    Key Record Dates
Results First Posted: February 8, 2019
Last Update Posted: February 8, 2019
Last Verified: September 2018
Additional relevant MeSH terms:
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Leukemia, Myelomonocytic, Chronic
Myelodysplastic Syndromes
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