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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Leukemia, Myeloid, Acute

Intervention / Treatment
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* Drug: Volasertib


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 3 Months
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Volasertib<br> | Drug: Volasertib<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

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