Clinical trial NCT05772559: Acute Myeloid Leukemia At Initial Diagnosis and/or Relapse in Children, Teenagers and Young Adults: Molecular Profiling, Multidrug Testing and MSC Interaction Studies
Official title: Acute Myeloid Leukemia At Initial Diagnosis and/or Relapse in Children, Teenagers and Young Adults: Molecular Profiling, Multidrug Testing and MSC Interaction Studies - ALARM3
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Acute Myeloid Leukemia
Genetic Predisposition to Disease
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2023-03-16
Enrollment: 500
Sex: ALL
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Children or young adult with 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

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.


Eligibility criteria: 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
* Chronic myeloid leukemia (CML)
* Lack of health insurance (French social security)
* Under protection (tutelle, curatelle or sauvegarde de justice)
* Pregnancy or breastfeeding

Primary outcomes:
measure: Number of somatic mutations in leukemic cells between diagnosis and relapse identified by Next-Generation Sequencing (NGS)
timeFrame: Up to 5 years
Secondary outcomes:
measure: Cumulative incidence of relapse (CIR) from remission status.
timeFrame: Up to 5 years
measure: Event Free Survival (EFS)
timeFrame: Up to 5 years
measure: Disease Free Survival (DFS)
timeFrame: Up to 5 years
measure: Number of mutations identified by WGS
timeFrame: Up to 5 years
measure: Expression profile (transcriptome) of mesenchymal stem cells
timeFrame: Up to 5 years
measure: Engraftment rate of primary leukemic cells
timeFrame: Up to 5 years
measure: Matched rate of genetic mutational (or expression) profile between derived cells from experimental models to primary leukemic cells
timeFrame: Up to 5 years
measure: Comparison of LSC signature profile of leukemic primary blasts at diagnosis and at relapse
timeFrame: Up to 5 years
measure: Cumulative incidence of relapse according to LSC signature profile of leukemic primary blasts at diagnosis and at relapse
timeFrame: Up to 5 years
measure: EFS according to LSC signature profile of leukemic primary blasts at diagnosis and at relapse
timeFrame: Up to 5 years
measure: DFS according to LSC signature profile of leukemic primary blasts at diagnosis and at relapse
timeFrame: Up to 5 years
measure: Ex vivo multidrug testing profile of leukemic primary blasts
timeFrame: Up ot 5 years
measure: Cumulative incidence of relapse according to ex vivo multidrug testing profile of leukemic primary blasts at diagnosis and relapse
timeFrame: Up to 5 years
measure: EFS according to ex vivo multidrug testing profile of leukemic primary blasts at diagnosis and relapse
timeFrame: Up to 5 years
measure: DFS according to ex vivo multidrug testing profile of leukemic primary blasts at diagnosis and relapse
timeFrame: Up to 5 years
measure: Mutational profile of patients
timeFrame: Up ot 5 years
measure: Percentage of MRD clearance
timeFrame: Up to 5 years
measure: Cumulative incidence of relapse according to MRD clearance
timeFrame: Up to 5 years
measure: EFS according to MRD clearance
timeFrame: Up to 5 years
measure: DFS according to MRD clearance
timeFrame: Up to 5 years
measure: Cumulative incidence of relapse according to MRD clearance
timeFrame: Up to 5 years
measure: EFS according to MRD clearance
timeFrame: Up to 5 years
measure: DFS according to MRD clearance
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU Amiens Picardie site Sud
city: Angers
country: France
facility: CHU Angers
city: Besançon
country: France
facility: Hopital Minjoz
city: Bordeaux
country: France
facility: CHU Pellegrin
city: Brest
country: France
facility: CHRU Morvan
city: Caen
country: France
facility: CHU Caen
city: Clermont-Ferrand
country: France
facility: CHU Estaing
city: Dijon
country: France
facility: CHU Francois Mitterand
city: Grenoble
country: France
facility: CHU Grenoble
city: La Réunion
country: France
facility: CHU de la Réunion
city: Lille
country: France
facility: Hopital Jeanne de Flandre - CHRU
city: Limoges
country: France
facility: CHU Limoges
city: Lyon
country: France
facility: HCL Lyon
city: Marseille
country: France
facility: Hôpital d'Enfants de la Timone
city: Montpellier
country: France
facility: CHU Montpellier
city: Nancy
country: France
facility: CHRU Nancy- Hopitaux de Brabois
city: Nantes
country: France
facility: CHU Nantes
city: Nice
country: France
facility: CHU Nice
city: Paris
country: France
facility: Hopital Robert Debré
city: Paris
country: France
facility: Hopital Trousseau
city: Poitiers
country: France
facility: CHU Poitiers
city: Reims
country: France
facility: Hopital Américain
city: Rennes
country: France
facility: CHU Hopital Sud
city: Rouen
country: France
facility: CHU Rouen
city: Saint-Étienne
country: France
facility: CHU Saint Etienne
city: Strasbourg
country: France
facility: Hopital Hautepierre
city: Toulouse
country: France
facility: CHU Toulouse
city: Tours
country: France
facility: CHRU Tours
Study officials:
References: