Research Study for Treatment of Children and Adolescents With Acute Myeloid Leukaemia 0-18 Years

Study Overview
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Brief Summary
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This study evaluates the effect of different induction courses in children and adolescents with newly diagnosed acute myeloid leukemia. In the first course patients are randomised to receive either standard anthracycline therapy with mitoxantrone or experimental DaunoXome. In the second course patients are randomised between standard treatment with ADxE (cytarabine, DaunoXome, etoposide) or experimental therapy with FLADx (fludarabine, cytarabine, DaunoXome).

Official Title
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NOPHO-DBH AML 2012 Protocol. Research Study for Treatment of Children and Adolescents With Acute Myeloid Leukaemia 0-18 Years

Conditions
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Pediatric Acute Myeloblastic Leukemia

Intervention / Treatment
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* Drug: Randomisation course 1 mitoxantrone versus DaunoXome
* Drug: Randomisation course 2 ADxE versus FLADx


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: AML as defined by the WHO diagnostic criteria Age < 19 years at time of diagnosis Written informed consent Exclusion Criteria: Previous chemotherapy or radiotherapy. This includes patient with secondary AML after previous cancer therapy AML secondary to previous bone marrow failure syndrome. Down syndrome (DS) Acute promyelocytic leukaemia (APL) Myelodysplastic syndrome (MDS) Juvenile Myelomonocytic Leukaemia (JMML) Known intolerance to any of the chemotherapeutic drugs in the protocol. Fanconi anaemia Major organ failure precluding administration of planned chemotherapy. Positive pregnancy test Lactating female or female of childbearing potential not using adequate contraception

Ages Eligible for Study
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Maximum Age: 18 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
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard arm MEC and ADxE<br>Standard protocol arm with mitoxantrone in first course (MEC) and standard ADxE treatment in course two | Drug: Randomisation course 1 mitoxantrone versus DaunoXome<br>* In course one with cytarabine and etoposide either mitoxantrone (standard) or DaunoXome (experimental) is given as anthracycline.<br>Drug: Randomisation course 2 ADxE versus FLADx<br>* The second course is randomised to either ADxE (standard arm) or FLADx<br>|
| Experimental: Experimental DxEC and standard ADxE<br>Experimental arm with DaunoXome in course one (DxEC) and standard ADxE treatment in course two | Drug: Randomisation course 1 mitoxantrone versus DaunoXome<br>* In course one with cytarabine and etoposide either mitoxantrone (standard) or DaunoXome (experimental) is given as anthracycline.<br>|
| Experimental: Standard arm MEC and experimental FLADx<br>Experimental arm with standard MEC in the first course (MEC) and experimental treatment with FLADx in course two | Drug: Randomisation course 2 ADxE versus FLADx<br>* The second course is randomised to either ADxE (standard arm) or FLADx<br>|
| Experimental: Experimental DxEC and experimental FLADx<br>Experimental treatment with DaunoXome in course one (DxEC) and experimental treatment with FLADx in course two | Drug: Randomisation course 1 mitoxantrone versus DaunoXome<br>* In course one with cytarabine and etoposide either mitoxantrone (standard) or DaunoXome (experimental) is given as anthracycline.<br>Drug: Randomisation course 2 ADxE versus FLADx<br>* The second course is randomised to either ADxE (standard arm) or FLADx<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Minimal residual disease | MRD will be measured by flow cytometry. In the randomisation for course 1 the endpoint is at day 22. In the randomisation for course 2 the endpoint is immediately before start of consolidation | On day 22 after the first induction and after second induction | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event-free survival | Event-free survival at five years | 5 years | 
| Acute toxicity | Hematological and other organ toxicity after each course | six months | 
| Long-term toxicity | Long-term toxicity in particular cardiac toxicity | 10 years | 
| Overall survival | Overall survival at five years | Five years |