Acute Myeloid Leukemia At Initial Diagnosis and/or Relapse in Children, Teenagers and Young Adults: Molecular Profiling, Multidrug Testing and MSC Interaction Studies
- Conditions
- Acute Myeloid LeukemiaGenetic Predisposition to Disease
- Interventions
- Other: Collection of blood sample of bone marrow (cohort 1)Other: Collection of blood sample of bone marrow (cohort 2 and 3)
- Registration Number
- NCT05772559
- Lead Sponsor
- Assistance Publique - Hôpitaux de Paris
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 500
- 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.
- Refuse to participate
- Chronic myeloid leukemia (CML)
- Lack of health insurance (French social security)
- Under protection (tutelle, curatelle or sauvegarde de justice)
- Pregnancy or breastfeeding
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Cohort 1 : Patients with acute myeloid leukemia Collection of blood sample of bone marrow (cohort 1) Patients with acute myeloid leukemia at initial diagnosis or relapse, aged less than 25 years Cohort 3 : Patients who undergo bone marrow aspirate Collection of blood sample of bone marrow (cohort 2 and 3) Patients who undergo bone marrow aspirate as part of standard of care but without AML nor predisposition to develop AML, as controls Cohort 2 : Patients with genetic predisposition to develop acute myeloid leukemia Collection of blood sample of bone marrow (cohort 2 and 3) -
- Primary Outcome Measures
Name Time Method Number of somatic mutations in leukemic cells between diagnosis and relapse identified by Next-Generation Sequencing (NGS) Up to 5 years
- Secondary Outcome Measures
Name Time Method Disease Free Survival (DFS) Up to 5 years Disease Free Survival (DFS) is defined as the time from remission status to relapse or death.
Number of mutations identified by WGS Up to 5 years Number of mutations identified by Whole-Genome-Sequencing (WGS) as compared to Next-Generation Sequencing (NGS) in leukemic cells
Expression profile (transcriptome) of mesenchymal stem cells Up to 5 years Expression profile (transcriptome) of mesenchymal stem cells at AML diagnosis and relapse compared to age matched controls without AML
EFS according to LSC signature profile of leukemic primary blasts at diagnosis and at relapse Up to 5 years Event Free Survival according to Leukemic Stem Cell (LSC) signature profile of leukemic primary blasts at diagnosis and at relapse
Engraftment rate of primary leukemic cells Up to 5 years Engraftment rate of primary leukemic cells in Patient-derived xenografts (PDX) or other experimental models
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 Up to 5 years Cumulative incidence of relapse according to Leukemic Stem Cell (LSC) signature profile of leukemic primary blasts at diagnosis and at relapse
EFS according to ex vivo multidrug testing profile of leukemic primary blasts at diagnosis and relapse Up to 5 years Event-Free Survival according to ex vivo multidrug testing profile of leukemic primary blasts at diagnosis and relapse
Percentage of MRD clearance Up to 5 years MRD clearance is defined as MRD below 10-3 Evaluated by flow cytometry and high sensitivity NGS (defined as MRD below 10-4) after each chemotherapy course
EFS according to MRD clearance Up to 5 years Evaluated by high sensitivity NGS at a threshold of 10-4
DFS according to LSC signature profile of leukemic primary blasts at diagnosis and at relapse Up to 5 years Disease-Free Survival (DFS) according to Leukemic Stem Cell (LSC) signature profile of leukemic primary blasts at diagnosis and at relapse
Ex vivo multidrug testing profile of leukemic primary blasts Up ot 5 years Comparison of ex vivo multidrug testing profile of leukemic primary blasts at diagnosis and relapse
Cumulative incidence of relapse 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 Up to 5 years Disease Free Survival according to ex vivo multidrug testing profile of leukemic primary blasts at diagnosis and relapse
Mutational profile of patients Up ot 5 years Comparison of mutational profile of patients with a predisposition syndrome compared to mutational profile of patients with AML at diagnosis and relapse
DFS according to MRD clearance Up to 5 years Evaluated by high sensitivity NGS at a threshold of 10-4
Cumulative incidence of relapse according to MRD clearance Up to 5 years Evaluated by high sensitivity NGS at a threshold of 10-4
Cumulative incidence of relapse (CIR) from remission status. Up to 5 years Relapse is defined as:
Bone marrow blasts ≥ 5% and/or evidence of extramedullary diseaseEvent Free Survival (EFS) Up to 5 years Event Free Survival (EFS) is defined as the time from start of chemotherapy to failure, relapse, or death which ever occurs first
Matched rate of genetic mutational (or expression) profile between derived cells from experimental models to primary leukemic cells Up to 5 years
Trial Locations
- Locations (28)
CHU Amiens Picardie site Sud
🇫🇷Amiens, France
CHU Poitiers
🇫🇷Poitiers, France
CHU Francois Mitterand
🇫🇷Dijon, France
CHU Grenoble
🇫🇷Grenoble, France
CHU Hopital Sud
🇫🇷Rennes, France
Hopital Hautepierre
🇫🇷Strasbourg, France
CHU Toulouse
🇫🇷Toulouse, France
CHU Nice
🇫🇷Nice, France
Hopital Américain
🇫🇷Reims, France
CHU Rouen
🇫🇷Rouen, France
Hôpital d'Enfants de la Timone
🇫🇷Marseille, France
Hopital Robert Debré
🇫🇷Paris, France
CHU Pellegrin
🇫🇷Bordeaux, France
HCL Lyon
🇫🇷Lyon, France
CHU Limoges
🇫🇷Limoges, France
CHU Nantes
🇫🇷Nantes, France
CHRU Morvan
🇫🇷Brest, France
CHU Estaing
🇫🇷Clermont-Ferrand, France
CHU de la Réunion
🇫🇷La Réunion, France
CHU Montpellier
🇫🇷Montpellier, France
CHU Saint Etienne
🇫🇷Saint-Étienne, France
CHU Angers
🇫🇷Angers, France
Hopital Trousseau
🇫🇷Paris, France
Hopital Minjoz
🇫🇷Besançon, France
CHU Caen
🇫🇷Caen, France
Hopital Jeanne de Flandre - CHRU
🇫🇷Lille, France
CHRU Nancy- Hopitaux de Brabois
🇫🇷Nancy, France
CHRU Tours
🇫🇷Tours, France