ALARM3: Acute Myeloid Leukemia At Initial Diagnosis and/or Relapse in Children, Teenagers and Young Adults: Molecular Profiling, Multidrug Testing and MSC Interaction Studies
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Study Design
Arms and Interventions
| Arm | 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)
|
Outcome Measures
Primary Outcome Measures
- Number of somatic mutations in leukemic cells between diagnosis and relapse identified by Next-Generation Sequencing (NGS) [Up to 5 years]
Secondary Outcome Measures
- 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 disease
- Event 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
- 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
- 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
- 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 [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 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
- 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]
- 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
- 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
Eligibility Criteria
Criteria
Inclusion Criteria:
-
0-25 years old
-
Newly diagnosed de novo or secondary Acute Myeloid Leukemia (AML) or
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Relapsed or refractory AML or
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Patients with genetic predisposition to develop AML or
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Patients without haematological malignancy nor AML genetic predisposition syndrome who undergo bone marrow aspirate as part of standard of care
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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:
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Refuse to participate
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Lack of health insurance (French social security)
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Under protection (tutelle, curatelle or sauvegarde de justice)
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Pregnancy or breastfeeding
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Assistance Publique - Hôpitaux de Paris
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- APHP220571