Clinical trial NCT02722135: A Study to Find a Safe Dose of Volasertib Given in Addition to Standard Salvage Chemotherapy in Children (Age 3 Months to Less Than 18 Years) With Acute Myeloid Leukaemia, in Whom Front-line Chemotherapy Failed
Official title: Open-label, Dose-escalating Trial to Evaluate the Tolerability, Toxicity, Safety, Pharmacokinetics, Pharmacodynamics and Activity of Volasertib Added to the Standard Intensive Salvage Chemotherapy Regimen With Liposomal Daunorubicine, Fludarabine and Cytarabine (DNX-FLA) Followed by Fludarabine and Cytarabine (FLA) in Children From 3 Months to Less Than 18 Years of Age With Acute Myeloid Leukaemia After Failure of the Front-line Therapy
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Leukemia, Myeloid, Acute
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2016-03-29
Enrollment: 0
Sex: ALL
Minimum age (years): 3
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an open-label, dose-escalating trial to evaluate the MTD and/or dose to be used for further development by evaluation of DLT in course 1 and the safety of volasertib when added to standard intensive salvage chemotherapy with DNX-FLA in paediatric patients with AML after failure of first-line therapy. Furthermore, data on efficacy and PK/PD of volasertib in paediatric patients with AML when added to standard intensive salvage chemotherapy will be collected.


Eligibility criteria: Inclusion criteria:

* Patients 3 months to \<18 years of age at the time of informed consent
* Patients with AML after failure of the front-line intensive AML therapy
* Lansky score at screening \>=50 for patients from 3 months to \<12 years
* Karnofsky score at screening \>=50 for patients from 12 to \<18 years
* Use of highly effective methods of birth-control, if sexually active
* Parents/legal guardians and patients have given written informed consent and informed assent suitable for the respective age group

Exclusion criteria:

* Down syndrome
* Acute promyelocytic leukaemia and treatment-related AML
* QTc prolongation
* LVSF \<30%
* Cardiac disease and/or dysfunction
* Active uncontrolled infection
* HIV infection, acute or chronic hepatitis
* Inadequate lab parameters
* Impaired renal function
* Pregnancy or nursing
* Further exclusion criteria apply

Primary outcomes:
measure: Determination of the maximal tolerated dose of volasertib or the recommended volasertib dose for further studies in combination with standard salvage therapy in paediatric patients with AML after failure of the front-line intensive chemotherapy regimen
timeFrame: 4 weeks
Secondary outcomes:
measure: Anti-leukaemic activity of volasertib in combination with standard salvage therapy
timeFrame: 8 weeks
measure: Event-free survival (EFS)
timeFrame: up to 5 years
measure: Overall survival (OS)
timeFrame: up to 5 years
measure: Number of patients with clinically relevant lab value changes of calcium (hyper- and/or hypocalcaemia) as judged by the investigator and reported as adverse events (Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or higher)
timeFrame: 8 weeks
measure: Number of patients with changes in cardiac activity (prolonged QTc interval) reported as clinically relevant observations (i.e. Adverse Events)
timeFrame: 8 weeks
measure: Predose concentration of volasertib before administration of second dose
timeFrame: 8 weeks
measure: Area under the concentration-time curve of volasertib
timeFrame: 8 weeks
measure: Terminal half-life of volasertib in plasma
timeFrame: 8 weeks
measure: Maximum concentration of volasertib
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Gent
country: Belgium
facility: Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: