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

September 11, 2018 updated by: Boehringer Ingelheim

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

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

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

16

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Marseille, France
        • 1230.33.33002 Boehringer Ingelheim Investigational Site
      • Paris, France
        • 1230.33.33001 Boehringer Ingelheim Investigational Site
  • Germany
      • Berlin, Germany
        • 1230.33.49011 Boehringer Ingelheim Investigational Site
      • Dresden, Germany
        • 1230.33.49002 Boehringer Ingelheim Investigational Site
      • Düsseldorf, Germany
        • 1230.33.49001 Boehringer Ingelheim Investigational Site
      • Frankfurt/Main, Germany
        • 1230.33.49005 Boehringer Ingelheim Investigational Site
      • Freiburg, Germany
        • 1230.33.49004 Boehringer Ingelheim Investigational Site
      • Hamburg, Germany
        • 1230.33.49010 Boehringer Ingelheim Investigational Site
      • Hannover, Germany
        • 1230.33.49008 Boehringer Ingelheim Investigational Site
      • Kassel, Germany
        • 1230.33.49012 Boehringer Ingelheim Investigational Site
      • Leipzig, Germany
        • 1230.33.49014 Boehringer Ingelheim Investigational Site
      • Mannheim, Germany
        • 1230.33.49009 Boehringer Ingelheim Investigational Site
      • München, Germany
        • 1230.33.49006 Boehringer Ingelheim Investigational Site
      • Ulm, Germany
        • 1230.33.49003 Boehringer Ingelheim Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
4 weeks
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 .
4 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
From randomisation until data cut-off (16Dec2016); up to 159 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Boehringer Ingelheim

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

November 6, 2013

Primary Completion (ACTUAL)

December 16, 2016

Study Completion (ACTUAL)

December 16, 2016

Study Registration Dates

First Submitted

October 1, 2013

First Submitted That Met QC Criteria

October 1, 2013

First Posted (ESTIMATE)

October 8, 2013

Study Record Updates

Last Update Posted (ACTUAL)

February 8, 2019

Last Update Submitted That Met QC Criteria

September 11, 2018

Last Verified

September 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1230.33
  • 2013-001290-24 (EUDRACT_NUMBER: EudraCT)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Myelodysplastic Syndromes

Clinical Trials on Azacitidine

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Mexico

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe