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NCT Number: NCT05772559

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

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.

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Key information

Conditions

Acute Myeloid Leukemia Disease Attributes Disease Susceptibility Genetic Predisposition to Disease Hematologic Diseases Hemic and Lymphatic Diseases Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Neoplasms Neoplasms by Histologic Type Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

Up to 25 year

Sex eligibility

All sexes

Study type

Observational

Primary location

CHU Amiens Picardie site Sud, Amiens, France

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Collection of blood sample of bone marrow (cohort 1)

Other
  • 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

Collection of blood sample of bone marrow (cohort 2 and 3)

Other
  • 1 additional tube of blood sample (cohort 2 and 3 at inclusion)
  • Bone marrow aspirate: 1 additional tube (cohort 2 and 3 at inclusion)

Primary outcomes

  1. 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

  1. Cumulative incidence of relapse (CIR) from remission status.

    Time frame: Up to 5 years

    Relapse is defined as:

    Bone marrow blasts ≥ 5% and/or evidence of extramedullary disease

  2. Event Free Survival (EFS)

    Time frame: 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

  3. Disease Free Survival (DFS)

    Time frame: Up to 5 years

    Disease Free Survival (DFS) is defined as the time from remission status to relapse or death.

  4. Number of mutations identified by WGS

    Time frame: Up to 5 years

    Number of mutations identified by Whole-Genome-Sequencing (WGS) as compared to Next-Generation Sequencing (NGS) in leukemic cells

  5. Expression profile (transcriptome) of mesenchymal stem cells

    Time frame: Up to 5 years

    Expression profile (transcriptome) of mesenchymal stem cells at AML diagnosis and relapse compared to age matched controls without AML

  6. Engraftment rate of primary leukemic cells

    Time frame: Up to 5 years

    Engraftment rate of primary leukemic cells in Patient-derived xenografts (PDX) or other experimental models

  7. Matched rate of genetic mutational (or expression) profile between derived cells from experimental models to primary leukemic cells

    Time frame: Up to 5 years

  8. Comparison of LSC signature profile of leukemic primary blasts at diagnosis and at relapse

    Time frame: Up to 5 years

  9. Cumulative incidence of relapse according to LSC signature profile of leukemic primary blasts at diagnosis and at relapse

    Time frame: 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

  10. EFS according to LSC signature profile of leukemic primary blasts at diagnosis and at relapse

    Time frame: Up to 5 years

    Event Free Survival according to Leukemic Stem Cell (LSC) signature profile of leukemic primary blasts at diagnosis and at relapse

  11. DFS according to LSC signature profile of leukemic primary blasts at diagnosis and at relapse

    Time frame: 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

  12. Ex vivo multidrug testing profile of leukemic primary blasts

    Time frame: Up ot 5 years

    Comparison of ex vivo multidrug testing profile of leukemic primary blasts at diagnosis and relapse

  13. Cumulative incidence of relapse according to ex vivo multidrug testing profile of leukemic primary blasts at diagnosis and relapse

    Time frame: Up to 5 years

  14. EFS according to ex vivo multidrug testing profile of leukemic primary blasts at diagnosis and relapse

    Time frame: Up to 5 years

    Event-Free Survival according to ex vivo multidrug testing profile of leukemic primary blasts at diagnosis and relapse

  15. DFS according to ex vivo multidrug testing profile of leukemic primary blasts at diagnosis and relapse

    Time frame: Up to 5 years

    Disease Free Survival according to ex vivo multidrug testing profile of leukemic primary blasts at diagnosis and relapse

  16. Mutational profile of patients

    Time frame: 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

  17. Percentage of MRD clearance

    Time frame: 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

  18. Cumulative incidence of relapse according to MRD clearance

    Time frame: Up to 5 years

    Evaluated by flow cytometry at a sensitivity threshold of 10-3

  19. EFS according to MRD clearance

    Time frame: Up to 5 years

    Evaluated by flow cytometry at a sensitivity threshold of 10-3

  20. DFS according to MRD clearance

    Time frame: Up to 5 years

    Evaluated by flow cytometry at a sensitivity threshold of 10-3

  21. Cumulative incidence of relapse according to MRD clearance

    Time frame: Up to 5 years

    Evaluated by high sensitivity NGS at a threshold of 10-4

  22. EFS according to MRD clearance

    Time frame: Up to 5 years

    Evaluated by high sensitivity NGS at a threshold of 10-4

  23. DFS according to MRD clearance

    Time frame: Up to 5 years

    Evaluated by high sensitivity NGS at a threshold of 10-4

Study contacts

Contact information is provided by the study sponsor or research team.

Arnaud PETIT, Pr

CONTACT

[email protected]

+33 1 44 73 53 14

Jérôme Lambert, Pr

CONTACT

[email protected]

142499742 ext. +33

Sponsors and collaborators

Lead sponsor

Assistance Publique - Hôpitaux de Paris

Other

Registry information

Official study 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

Acronym: ALARM3

Important dates

Study start
2023
Primary completion
2033
Study completion
2033
First posted
Mar 16, 2023
Registry last updated
Jun 26, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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