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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia; Genetic Predisposition to Disease
• Intervention / Treatment: Other: Collection of blood sample of bone marrow (cohort 1); Other: Collection of blood sample of bone marrow (cohort 2 and 3)

• Study Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

• Study Contact: Name: Arnaud PETIT, Pr; Phone Number: +33 1 44 73 53 14; Email: arnaud.petit@aphp.fr
• Study Contact Backup: Name: Jérôme Lambert, Pr; Phone Number: +33 142499742; Email: jerome.lambert@u-paris.fr

Study Locations

• France
  • Amiens, France
    • Recruiting
    • CHU Amiens Picardie Site Sud
    • Contact: Camille Leglise, MD
  • Angers, France
    • Recruiting
    • CHU Angers
    • Contact: Isabelle Pellier, MD
  • Besançon, France
    • Recruiting
    • Hopital Minjoz
    • Contact: Nathalie Cheikh, MD
  • Bordeaux, France
    • Recruiting
    • CHU Pellegrin
    • Contact: Stéphane Ducassou, MD
  • Brest, France
    • Recruiting
    • CHRU Morvan
    • Contact: Liana CARAUSU, MD
  • Caen, France
    • Recruiting
    • CHU caen
    • Contact: Jérémie Rouger, MD
  • Clermont-Ferrand, France
    • Recruiting
    • CHU Estaing
    • Contact: Justyna KANOLD, MD
  • Dijon, France
    • Recruiting
    • Chu Francois Mitterand
    • Contact: Claire Desplante, MD
  • Grenoble, France
    • Recruiting
    • CHU Grenoble
    • Contact: Corinne Armari Alla, MD
  • La Réunion, France
    • Recruiting
    • CHU de la réunion
    • Contact: Yves REGUERRE, MD
  • Lille, France
    • Recruiting
    • Hôpital Jeanne de Flandre - CHRU
    • Contact: Brigitte Nelken, MD
  • Limoges, France
    • Recruiting
    • CHU Limoges
    • Contact: Thomas Louvray, MD
  • Lyon, France
    • Recruiting
    • HCL Lyon
    • Contact: Cécile Renard, MD
  • Marseille, France
    • Recruiting
    • Hôpital d'Enfants de la Timone
    • Contact: Paul Saultier, MD
  • Montpellier, France
    • Recruiting
    • CHU Montpellier
    • Contact: Stéphanie Haouy, MD
  • Nancy, France
    • Recruiting
    • CHRU Nancy- Hopitaux de Brabois
    • Contact: Marion Lubnau, MD
  • Nantes, France
    • Recruiting
    • CHU Nantes
    • Contact: Fanny Rialland, MD
  • Nice, France
    • Recruiting
    • CHU Nice
    • Contact: Marilyne Poirée, MD
  • Paris, France
    • Recruiting
    • Hôpital Trousseau
    • Contact: Arnaud Petit, MD PhD
  • Paris, France
    • Recruiting
    • Hôpital Robert Debré
    • Contact: Marion Strullu, MD
  • Poitiers, France
    • Recruiting
    • CHU Poitiers
    • Contact: Frédéric Millot, MD
  • Reims, France
    • Recruiting
    • Hopital Americain
    • Contact: Claire PLUCHART, MD
  • Rennes, France
    • Recruiting
    • CHU Hopital Sud
    • Contact: Virginie Gandemer, MD
  • Rouen, France
    • Recruiting
    • CHU Rouen
    • Contact: Nimrod Buchbinde, MD
  • Saint-Étienne, France
    • Recruiting
    • CHU Saint Etienne
    • Contact: Sandrine Thouvenin-Doulet, MD
  • Strasbourg, France
    • Recruiting
    • Hôpital Hautepierre
    • Contact: Catherine Paillard, MD
  • Toulouse, France
    • Recruiting
    • CHU Toulouse
    • Contact: Marlène Pasquet, MD
  • Tours, France
    • Recruiting
    • CHRU Tours
    • Contact: Julien LEJEUNE, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 25 years (Child, Adult)
• Accepts Healthy Volunteers: No

• 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

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cohort 1 : Patients with acute myeloid leukemia; 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); 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
Cohort 2 : Patients with genetic predisposition to develop acute myeloid leukemia	Other: Collection of blood sample of bone marrow (cohort 2 and 3); 1 additional tube of blood sample (cohort 2 and 3 at inclusion); Bone marrow aspirate: 1 additional tube (cohort 2 and 3 at inclusion)
Cohort 3 : Patients who undergo bone marrow aspirate; 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); 1 additional tube of blood sample (cohort 2 and 3 at inclusion); Bone marrow aspirate: 1 additional tube (cohort 2 and 3 at inclusion)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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
Percentage of MRD clearance	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	Up to 5 years
Cumulative incidence of relapse according to MRD clearance	Evaluated by flow cytometry at a sensitivity threshold of 10-3	Up to 5 years
EFS according to MRD clearance	Evaluated by flow cytometry at a sensitivity threshold of 10-3	Up to 5 years
DFS according to MRD clearance	Evaluated by flow cytometry at a sensitivity threshold of 10-3	Up to 5 years
Cumulative incidence of relapse according to MRD clearance	Evaluated by high sensitivity NGS at a threshold of 10-4	Up to 5 years
EFS according to MRD clearance	Evaluated by high sensitivity NGS at a threshold of 10-4	Up to 5 years
DFS according to MRD clearance	Evaluated by high sensitivity NGS at a threshold of 10-4	Up to 5 years

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2023
• Primary Completion (Estimated): May 31, 2033
• Study Completion (Estimated): May 31, 2033

Study Registration Dates

• First Submitted: March 6, 2023
• First Submitted That Met QC Criteria: March 6, 2023
• First Posted (Actual): March 16, 2023

Study Record Updates

• Last Update Posted (Actual): June 26, 2024
• Last Update Submitted That Met QC Criteria: June 24, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Hematologic Diseases; Disease Susceptibility; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Genetic Predisposition to Disease
• Other Study ID Numbers: APHP220571

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No