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

Boehringer Ingelheim

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Conditions

Leukemia, Myeloid, Acute

Interventions

VolasertibDRUG

Eligibility

Sex: ALLMin age: 3 MonthsMax age: 17 Years

Medical Language ↔ Plain English

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

Locations (1)

Boehringer Ingelheim Investigational Site

Ghent, Belgium

Outcomes

Primary Outcomes

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

Time frame: 4 weeks

Secondary Outcomes

Anti-leukaemic activity of volasertib in combination with standard salvage therapy

Time frame: 8 weeks

Event-free survival (EFS)

Time frame: up to 5 years

Overall survival (OS)

Time frame: up to 5 years

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)

Time frame: 8 weeks

Number of patients with changes in cardiac activity (prolonged QTc interval) reported as clinically relevant observations (i.e. Adverse Events)

Time frame: 8 weeks

Predose concentration of volasertib before administration of second dose

Time frame: 8 weeks

Area under the concentration-time curve of volasertib

Time frame: 8 weeks

Terminal half-life of volasertib in plasma

Time frame: 8 weeks

Maximum concentration of volasertib

Data from ClinicalTrials.gov

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