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

Leukemia, Myeloid, Acute Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02722135
• Other study ID #: 1230.28
• Secondary ID: 2015-004625-14
• Status: Withdrawn
• Phase: Phase 1
• First received: March 23, 2016
• Last updated: January 26, 2017
• Start date: November 2016
• Est. completion date: September 2018

Study information

• Verified date: January 2017
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: September 2018
• Est. primary completion date: May 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Months to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• Volasertib

Locations

Country	Name	City	State
Belgium	Boehringer Ingelheim Investigational Site	Gent

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		4 weeks
Secondary	Anti-leukaemic activity of volasertib in combination with standard salvage therapy		8 weeks
Secondary	Event-free survival (EFS)		up to 5 years
Secondary	Overall survival (OS)		up to 5 years
Secondary	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)		8 weeks
Secondary	Number of patients with changes in cardiac activity (prolonged QTc interval) reported as clinically relevant observations (i.e. Adverse Events)		8 weeks
Secondary	Predose concentration of volasertib before administration of second dose		8 weeks
Secondary	Area under the concentration-time curve of volasertib		8 weeks
Secondary	Terminal half-life of volasertib in plasma		8 weeks
Secondary	Maximum concentration of volasertib		8 weeks