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

Assistance Publique - Hôpitaux de Paris28 sites in 1 country500 target enrollmentMay 31, 2023

ConditionsAcute Myeloid Leukemia Genetic Predisposition to Disease

Overview

Phase: Not Applicable
Intervention: Not specified
Conditions: Acute Myeloid Leukemia
Sponsor: Assistance Publique - Hôpitaux de Paris
Enrollment: 500
Locations: 28
Primary Endpoint: Number of somatic mutations in leukemic cells between diagnosis and relapse identified by Next-Generation Sequencing (NGS)
Status: Recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

May 31, 2023

End Date

May 31, 2033

Last Updated

last year

Study Type

Observational

Sex

All

Investigators

Sponsor

Assistance Publique - Hôpitaux de Paris

Responsible Party

Sponsor

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

Outcomes

Primary Outcomes

Number of somatic mutations in leukemic cells between diagnosis and relapse identified by Next-Generation Sequencing (NGS)

Time Frame: Up to 5 years

Secondary Outcomes

Disease Free Survival (DFS)(Up to 5 years)
Number of mutations identified by WGS(Up to 5 years)
Expression profile (transcriptome) of mesenchymal stem cells(Up to 5 years)
EFS according to LSC signature profile of leukemic primary blasts at diagnosis and at relapse(Up to 5 years)
Engraftment rate of 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(Up to 5 years)
EFS according to ex vivo multidrug testing profile of leukemic primary blasts at diagnosis and relapse(Up to 5 years)
Percentage of MRD clearance(Up to 5 years)
EFS according to MRD clearance(Up to 5 years)
DFS according to 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(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)
DFS according to ex vivo multidrug testing profile of leukemic primary blasts at diagnosis and relapse(Up to 5 years)
Mutational profile of patients(Up ot 5 years)
DFS according to MRD clearance(Up to 5 years)
Cumulative incidence of relapse according to MRD clearance(Up to 5 years)
Cumulative incidence of relapse (CIR) from remission status.(Up to 5 years)
Event Free Survival (EFS)(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)