Clinical trial NCT01957644: Phase I Dose Escalation Trial of Volasertib in Combination With Azacitidine in Patients With MDS or CMML
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Myelodysplastic Syndromes
Leukemia, Myelomonocytic, Chronic
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2013-10-08
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Determination of the Maximum Tolerated Dose (MTD) Based on the Occurrence of Dose-limiting Toxicity (DLT) in Cycle 1
timeFrame: 4 weeks
measure: Number of Participants With Dose Limiting Toxicities (DLT) in Cycle 1
timeFrame: 4 weeks
Secondary outcomes:
measure: Percentage of Patients With Objective Response (OR)
timeFrame: From randomisation until data cut-off (16Dec2016); up to 159 weeks
Other outcomes:
Locations:
city: Marseille
country: France
facility: 1230.33.33002 Boehringer Ingelheim Investigational Site
city: Paris
country: France
facility: 1230.33.33001 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1230.33.49011 Boehringer Ingelheim Investigational Site
city: Dresden
country: Germany
facility: 1230.33.49002 Boehringer Ingelheim Investigational Site
city: Düsseldorf
country: Germany
facility: 1230.33.49001 Boehringer Ingelheim Investigational Site
city: Frankfurt/Main
country: Germany
facility: 1230.33.49005 Boehringer Ingelheim Investigational Site
city: Freiburg
country: Germany
facility: 1230.33.49004 Boehringer Ingelheim Investigational Site
city: Hamburg
country: Germany
facility: 1230.33.49010 Boehringer Ingelheim Investigational Site
city: Hannover
country: Germany
facility: 1230.33.49008 Boehringer Ingelheim Investigational Site
city: Kassel
country: Germany
facility: 1230.33.49012 Boehringer Ingelheim Investigational Site
city: Leipzig
country: Germany
facility: 1230.33.49014 Boehringer Ingelheim Investigational Site
city: Mannheim
country: Germany
facility: 1230.33.49009 Boehringer Ingelheim Investigational Site
city: München
country: Germany
facility: 1230.33.49006 Boehringer Ingelheim Investigational Site
city: Ulm
country: Germany
facility: 1230.33.49003 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: