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

Phase 1

• Conditions: Acute Myloid Leukaemia; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2015-004625-14-NL
• Lead Sponsor: Boehringer Ingelheim bv

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-05-09
• Last Update Posted: 9 January 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 52

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
Are the trial subjects under 18? yes
Number of subjects for this age range: 42
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To define 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;Secondary Objective: To collect data on efficacy and PK/PD of volasertib in paediatric patients with AML when added to standard intensive salvage chemotherapy;Primary end point(s): 1: Determination of the MTD 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<br>;Timepoint(s) of evaluation of this end point: 1: 4 weeks<br>

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1: 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 (CTCAE grade 3 or higher)<br><br>2: Number of patients with changes in cardiac activity (prolonged QTc interval) reported as clinically relevant observations (i.e. AEs)<br><br>3: Anti-leukaemic activity of volasertib in combination with standard salvage therapy<br><br>4: Event-free survival (EFS)<br><br>5: Overall survival (OS)<br><br>6: Pharmacokinetic evaluation of volasertib<br>;Timepoint(s) of evaluation of this end point: 1: 8 weeks<br><br>2: 8 weeks<br><br>3: 8 weeks<br><br>4: up to 5 years<br><br>5: up to 5 years<br><br>6: 8 weeks<br>