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

NCT01957644 | Terminated Phase 1 Results

• 2 other identifiers: 1230.332013-001290-24
• Study Type: interventional
• Target: 16
• Locations: 2 countries
• Sites: 14

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

Conditions

Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic

Outcome Measures

Primary Outcomes (2)

• Determination of the Maximum Tolerated Dose (MTD) Based on the Occurrence of Dose-limiting Toxicity (DLT) in Cycle 1

  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

  Number of participants with Dose Limiting Toxicities (DLT) in Cycle 1 (escalation part to determine MTD) is presented .

  4 weeks

Secondary Outcomes (1)

• Percentage of Patients With Objective Response (OR)

  From randomisation until data cut-off (16Dec2016); up to 159 weeks

Study Arms (3)

Schedule A

EXPERIMENTAL

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

Schedule B

EXPERIMENTAL

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

Schedule C

EXPERIMENTAL

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

Interventions

Azacitidine DRUG

Schedule A; Schedule B; Schedule C

Volasertib DRUG

Schedule A; Schedule B; Schedule C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (14)

1230.33.33002 Boehringer Ingelheim Investigational Site

Marseille, France

Location

1230.33.33001 Boehringer Ingelheim Investigational Site

Paris, France

Location

1230.33.49011 Boehringer Ingelheim Investigational Site

Berlin, Germany

Location

1230.33.49002 Boehringer Ingelheim Investigational Site

Dresden, Germany

Location

1230.33.49001 Boehringer Ingelheim Investigational Site

Düsseldorf, Germany

Location

1230.33.49005 Boehringer Ingelheim Investigational Site

Frankfurt am Main, Germany

Location

1230.33.49004 Boehringer Ingelheim Investigational Site

Freiburg im Breisgau, Germany

Location

1230.33.49010 Boehringer Ingelheim Investigational Site

Hamburg, Germany

Location

1230.33.49008 Boehringer Ingelheim Investigational Site

Hanover, Germany

Location

1230.33.49012 Boehringer Ingelheim Investigational Site

Kassel, Germany

Location

1230.33.49014 Boehringer Ingelheim Investigational Site

Leipzig, Germany

Location

1230.33.49009 Boehringer Ingelheim Investigational Site

Mannheim, Germany

Location

1230.33.49006 Boehringer Ingelheim Investigational Site

München, Germany

Location

1230.33.49003 Boehringer Ingelheim Investigational Site

Ulm, Germany

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic

Interventions

Azacitidine; BI 6727

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Limitations and Caveats

The sponsor discontinued the development of volasertib on 25 Nov 2016 and this trial was discontinued on 16 Dec 2016 for non-clinical reasons. The number of patients enrolled in Part 2 of the study was too small for a meaningful analysis.

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2013
• First Posted: October 8, 2013
• Study Start: November 6, 2013
• Primary Completion: December 16, 2016
• Study Completion: December 16, 2016
• Last Updated: February 8, 2019
• Results First Posted: February 8, 2019

Record last verified: 2018-09

Locations

FR (2); DE (12)