Acute Myeloid Leukemia At Initial Diagnosis and/or Relapse in Children, Teenagers and Young Adults: Molecular Profiling, Multidrug Testing and MSC Interaction Studies

Study Overview
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Brief Summary
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Pediatric acute myeloid leukemias are disease with poor prognosis (overall survival of 60-75%) and high relapse rate of 35-45% require further understanding of the underlying biological mechanisms. The main objective of this study is to establish a biological collection to evaluate the genomic profiling of leukemic cells from primary blasts at diagnosis and/or relapse to improve identification of the main genetic hits involved in resistance and could predict a high risk of relapse. Other objectives include the study of bone marrow mesenchymal stem cells and ex vivo drug testing.

Official Title
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Acute Myeloid Leukemia At Initial Diagnosis and/or Relapse in Children, Teenagers and Young Adults: Molecular Profiling, Multidrug Testing and MSC Interaction Studies - ALARM3

Conditions
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Acute Myeloid Leukemia, Genetic Predisposition to Disease

Intervention / Treatment
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* Other: Collection of blood sample of bone marrow (cohort 1)
* Other: Collection of blood sample of bone marrow (cohort 2 and 3)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 0-25 years old Newly diagnosed de novo or secondary Acute Myeloid Leukemia (AML) or Relapsed or refractory AML or Patients with genetic predisposition to develop AML or Patients without haematological malignancy nor AML genetic predisposition syndrome who undergo bone marrow aspirate as part of standard of care Signed informed consent of parents for patients aged less than 18 years old or signed informed consent of the patient for patients aged 18 and over. Exclusion Criteria: Refuse to participate Lack of health insurance (French social security) Under protection (tutelle, curatelle or sauvegarde de justice) Pregnancy or breastfeeding

Ages Eligible for Study
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Maximum Age: 25 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cohort 1 : Patients with acute myeloid leukemia<br>Patients with acute myeloid leukemia at initial diagnosis or relapse, aged less than 25 years | Other: Collection of blood sample of bone marrow (cohort 1)<br>* 3 additional tubes of blood sample (cohort 1), at diagnosis and upon relapse if relapse occurs Bone marrow aspirate : 3 additional tubes (cohort 1), at diagnosis and upon relapse if relapse occurs<br>|
| Cohort 2 : Patients with genetic predisposition to develop acute myeloid leukemia<br> | Other: Collection of blood sample of bone marrow (cohort 2 and 3)<br>* 1 additional tube of blood sample (cohort 2 and 3 at inclusion) Bone marrow aspirate: 1 additional tube (cohort 2 and 3 at inclusion)<br>|
| Cohort 3 : Patients who undergo bone marrow aspirate<br>Patients who undergo bone marrow aspirate as part of standard of care but without AML nor predisposition to develop AML, as controls | Other: Collection of blood sample of bone marrow (cohort 2 and 3)<br>* 1 additional tube of blood sample (cohort 2 and 3 at inclusion) Bone marrow aspirate: 1 additional tube (cohort 2 and 3 at inclusion)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of somatic mutations in leukemic cells between diagnosis and relapse identified by Next-Generation Sequencing (NGS) |  | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative incidence of relapse (CIR) from remission status. | Relapse is defined as: Bone marrow blasts ≥ 5% and/or evidence of extramedullary disease | Up to 5 years | 
| Event Free Survival (EFS) | Event Free Survival (EFS) is defined as the time from start of chemotherapy to failure, relapse, or death which ever occurs first | Up to 5 years | 
| Disease Free Survival (DFS) | Disease Free Survival (DFS) is defined as the time from remission status to relapse or death. | Up to 5 years | 
| Number of mutations identified by WGS | Number of mutations identified by Whole-Genome-Sequencing (WGS) as compared to Next-Generation Sequencing (NGS) in leukemic cells | Up to 5 years | 
| Expression profile (transcriptome) of mesenchymal stem cells | Expression profile (transcriptome) of mesenchymal stem cells at AML diagnosis and relapse compared to age matched controls without AML | Up to 5 years | 
| Engraftment rate of primary leukemic cells | Engraftment rate of primary leukemic cells in Patient-derived xenografts (PDX) or other experimental models | Up to 5 years | 
| Matched rate of genetic mutational (or expression) profile between derived cells from experimental models to primary leukemic cells |  | Up to 5 years | 
| Comparison of LSC signature profile of leukemic primary blasts at diagnosis and at relapse |  | Up to 5 years | 
| Cumulative incidence of relapse according to LSC signature profile of leukemic primary blasts at diagnosis and at relapse | Cumulative incidence of relapse according to Leukemic Stem Cell (LSC) signature profile of leukemic primary blasts at diagnosis and at relapse | Up to 5 years | 
| EFS according to LSC signature profile of leukemic primary blasts at diagnosis and at relapse | Event Free Survival according to Leukemic Stem Cell (LSC) signature profile of leukemic primary blasts at diagnosis and at relapse | Up to 5 years | 
| DFS according to LSC signature profile of leukemic primary blasts at diagnosis and at relapse | Disease-Free Survival (DFS) according to Leukemic Stem Cell (LSC) signature profile of leukemic primary blasts at diagnosis and at relapse | Up to 5 years | 
| Ex vivo multidrug testing profile of leukemic primary blasts | Comparison of ex vivo multidrug testing profile of leukemic primary blasts at diagnosis and relapse | Up ot 5 years | 
| Cumulative incidence of relapse according to ex vivo multidrug testing profile of leukemic primary blasts at diagnosis and relapse |  | Up to 5 years | 
| EFS according to ex vivo multidrug testing profile of leukemic primary blasts at diagnosis and relapse | Event-Free Survival according to ex vivo multidrug testing profile of leukemic primary blasts at diagnosis and relapse | Up to 5 years | 
| DFS according to ex vivo multidrug testing profile of leukemic primary blasts at diagnosis and relapse | Disease Free Survival according to ex vivo multidrug testing profile of leukemic primary blasts at diagnosis and relapse | Up to 5 years | 
| Mutational profile of patients | Comparison of mutational profile of patients with a predisposition syndrome compared to mutational profile of patients with AML at diagnosis and relapse | Up ot 5 years |