This study has been transitioned to CTIS with ID 2024-518254-16-00 check the CTIS register for the current data. The primary aim of the NOPHO-DBH AML 2012 study is to improve EFS and OS in children with AML. To improve outcome, an intensified…
ID
Source
Brief title
Condition
- Leukaemias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is the MRD level at day 22 from start of the course.
Secondary outcome
Secondary outcome measures in both studies include EFS, OS, remission rate and
toxicity.
Background summary
The outcome of paediatric acute myeloid leukaemia is still unsatisfactory with
an overall survival around 70% and a relapse rate of 30-40% after primary
treatment.
Study objective
This study has been transitioned to CTIS with ID 2024-518254-16-00 check the CTIS register for the current data.
The primary aim of the NOPHO-DBH AML 2012 study is to improve EFS and OS in
children with AML. To improve outcome, an intensified induction regimen will be
given and a response guided risk-group stratification using flow cytometric
minimal residual disease measurements to evaluate therapy response will be
used. Patients with a poor response to the two induction courses will be
assigned to the high-risk group and receive consolidation therapy including
stem cell transplantation whereas those with a good response will be given
three chemotherapy courses as consolidation therapy. An exception are patients
with good response and inv(16), who will not be given HAM and thus receive two
consolidation courses only. The only other cytogenetic feature that will affect
risk stratification is the presence of an FLT3-ITD mutation which, when not
associated with concomitant nucleophosmin (NPM1) mutation, will stratify
patients to the high-risk group.
Effective induction therapy is crucial for outcome in AML and MRD levels
following induction are highly predictive of outcome.
Study design
randomised clinical trial
Intervention
NOPHO-DBH AML 2012 includes two randomised studies that both address the
efficacy of induction therapy.
The first study is based on the induction course from the Japanese AML99 trial
and compares the efficacy of mitoxantrone and DaunoXome in the first treatment
course. The primary outcome measure is the MRD level on day 22 from start of
the course.
The second study compares ADxE (low-dose cytarabine, DaunoXome and etoposide)
with FLADx (fludarabine, high-dose cytarabine and DaunoXome) as the second
induction course.
Per the amendment dated 13-12-2018 the 1st randomisation is closed, and all
patients will receive MEC as 1st induction course. In the 2nd induction course
DaunoXome can be replaced by Daunorubicine, in case DaunoXome is not available.
Per 09-08-2021 the 2nd randomisation is also closed. All patients will receive
standard ADxE as 2nd induction course. DaunoXome can be replaced by
Daunorubicin in case DaunoXome is not available.
Study burden and risks
Children and adolescents with AML need to be treated. With respect to burden
and risks this protocol does not differ from other treatments for AML as has
been used in the past in the Netherlands. This protocol has safety guidelines
to monitor the outcome.
Rondvägen 10
Göteborg 41685
SE
Rondvägen 10
Göteborg 41685
SE
Listed location countries
Age
Inclusion criteria
Patients are eligible for the study if they fulfil all three criteria below, 1)
AML as defined by the diagnostic criteria in section 16
2) Age < 19 years at time of diagnosis
3) Written informed consent
Exclusion criteria
Patients are excluded if any of the criteria below are present
1) Previous chemotherapy or radiotherapy.
2) AML secondary to previous bone marrow failure syndrome.
3) Down syndrome (DS).
4) Acute promyelocytic leukaemia (APL).
5) Myelodysplastic syndrome (MDS).
6) Juvenile Myelomonocytic Leukaemia (JMML).
7) Known intolerance to any of the chemotherapeutic drugs in the protocol.
8) Fanconi anaemia.
9) Major organ failure precluding administration of planned chemotherapy.
10) Positive pregnancy test.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2024-518254-16-00 |
| EudraCT | EUCTR2012-002934-35-NL |
| ClinicalTrials.gov | NCT01828489 |
| CCMO | NL41711.029.13 |