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

Acute Myeloid Leukemia Clinical Trial

— ALARM3  

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05772559
• Other study ID #: APHP220571
• Status: Not yet recruiting
• Start date: March 2023
• Est. completion date: March 2033

Study information

• Verified date: February 2023
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Arnaud PETIT, Pr
• Phone: +33 1 44 73 53 14
• Email: arnaud.petit[@]aphp.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 500
• Est. completion date: March 2033
• Est. primary completion date: March 2033
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 25 Years

Eligibility

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

• Lack of health insurance (French social security)

• Under protection (tutelle, curatelle or sauvegarde de justice)

• Pregnancy or breastfeeding

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Genetic Predisposition to Disease
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

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
• 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)

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of somatic mutations in leukemic cells between diagnosis and relapse identified by Next-Generation Sequencing (NGS)		Up to 5 years
Secondary	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
Secondary	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
Secondary	Disease Free Survival (DFS)	Disease Free Survival (DFS) is defined as the time from remission status to relapse or death.	Up to 5 years
Secondary	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
Secondary	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
Secondary	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
Secondary	Matched rate of genetic mutational (or expression) profile between derived cells from experimental models to primary leukemic cells		Up to 5 years
Secondary	Comparison of LSC signature profile of leukemic primary blasts at diagnosis and at relapse		Up to 5 years
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Cumulative incidence of relapse according to ex vivo multidrug testing profile of leukemic primary blasts at diagnosis and relapse		Up to 5 years
Secondary	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
Secondary	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
Secondary	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