Back to resultsStudy of the Medullary Microenvironment in Acute Childhood Leukemia (MILA)
Primary Purpose
Acute Lymphoid Leukemia, Acute Myeloid Leukemia in Children
Status
Not yet recruiting
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Biological sampling in patients
Biological sampling in control patients
Sponsored by
About this trial
This is an interventional diagnostic trial for Acute Lymphoid Leukemia
Eligibility Criteria
Inclusion Criteria: for patients with AL: Child with acute lymphoblastic or myeloblastic leukemia at diagnosis Not having received prior hematological treatment Aged 1 to 15 years old Whose 2 parents, or the holder of parental authority, have signed a consent enlightened. Affiliated patient or beneficiary of a social security scheme. Control group patients: Child undergoing orthopedic surgery exposing the bone marrow (osteotomy of the pelvis). Aged between 1 and 15 years old. Having no pathology of hematological origin. Not having received any treatment that could interfere with the functioning of the bone marrow. Whose 2 parents or the holder of parental authority have signed a consent enlightened. Affiliated patient or beneficiary of a social security scheme. Exclusion Criteria: for patients with AL: Patient under 1 year old and over 15 years old. Contraindication to myelogram. Absence of signature of the informed consent by the 2 parents or the holder of parental authority. Patients with relapsed acute lymphoblastic or myeloblastic leukemia. Having received prior hematological treatments. Parents with physical or mental condition not allowing to understand the informed consent. Control group patients Patient under 1 year old and over 15 years old. Having an underlying haematological pathology. Absence of signature of the informed consent by the 2 parents or the holder of parental authority. Having received prior hematological treatments. Parents with physical or mental condition not allowing to understand informed consent.
Sites / Locations
- Service d'hématologie biologique-CHRU TOURS
- Service d'onco-hématologie pédiatrique -CHRU Tours
- Service de chirurgie orthopédique pédiatrique -CHRU TOURS
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Other
Arm Label
Patients with acute leukemias
Control group
Arm Description
Children with acute lymphoid leukemia B, acute lymphoid leukemia -T or acute myeloid leukemia
Children without blood diseases
Outcomes
Primary Outcome Measures
Oxygen Consumption Rate
Difference in oxidative phosphorylation measured by OCR (Oxygen Consumption Rate) in pmol/min/nd DNA between the mesenchymal stromal stem cells (MSCs) of children with Acute Leukemia and those of children without blood diseases.
Secondary Outcome Measures
Difference in Extra Cellular Acidification Rate
Difference in glycolysis, measured by the ECAR (Extra Cellular Acification Rate) in mpH/min/ng DNA between the MSCs of children with AL and those of children without hematological disease.
Difference in Reactive Oxygen Species
Difference in oxidative metabolism thanks to the measurement of reactive oxygen species (ROS), measured in MIF/isotype, between MSCs of children with AL and those of children without hematological disease
Difference in doubling time in culture
The difference in doubling time in culture (measured in days) between the MSCs of children with LA and those of children free of hemopathy. At each passage, the number of living and dead MSCs will be counted.
Difference in Immunophenotypic profile
The difference in immunophenotypic profile (cytometry, immunofluorescence) between MSCs of children with AL and those of children without hematological disease. Use of a panel of monoclonal antibodies directed against various membrane antigens (CD45, CD34, CD14, CD90, CD73, CD105).
Difference in mutational profiles between MSCs and leukemia cells
Difference in mutational profiles between MSCs and leukemia cells from children with AL. Comparison of mutations acquired by leukemic cells compared to stromal cells by an NGS-type high-throughput sequencing approach.
Differences in transcriptomic signatures between MSCs and MSC subpopulations
Differences in transcriptomic signatures between MSCs and MSC subpopulations of children with AL and those of children without hematological disease. The RNAs of the MSCs obtained after culture will be extracted then reverse-transcribed into cDNA. The quality control of the extracted RNAs will be carried out on a Bioanalyzer (Agilent). Transcriptome analysis of the MSC pool will be performed by RNA Seq/NGS. Transcriptomic identification of MSC subpopulations will be performed by single-cell RNAseq/NGS.
Differences in cytokine profiles within the bone marrow
Differences in cytokine profiles in the bone marrow and in the blood, measured in ng/mL, between children with AL and children without hematological disease.ELISA-like assay of IL-3, IL-6, IL-7, IL-8, IL-10, IL-15, TGF-bêta, IFN-gamma
Full Information
NCT ID
NCT05792007
First Posted
March 8, 2023
Last Updated
August 9, 2023
Sponsor
University Hospital, Tours
1. Study Identification
Unique Protocol Identification Number
NCT05792007
Brief Title
Study of the Medullary Microenvironment in Acute Childhood Leukemia
Acronym
MILA
Official Title
Etude du Microenvironnement médullaire Dans Les Leucémies Aiguës de l'Enfant
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
September 15, 2023 (Anticipated)
Primary Completion Date
May 1, 2026 (Anticipated)
Study Completion Date
May 1, 2028 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Tours
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Acute leukemia (AL) is the most common cancer in children. Despite the optimization of chemotherapy treatments and the development of supportive care, a certain number of LAs relapse and/or progress to death of the child. It therefore seems essential to try to better understand the physiopathology and the mechanisms of resistance to treatment of these diseases.
Detailed Description
Acute leukemia (AL) is the most common cancer in children. Despite the optimization of chemotherapy treatments and the development of supportive care, a certain number of AL's relapse and/or progress to death of the child. It therefore seems essential to try to better understand the physiopathology and the mechanisms of resistance to treatment of these diseases. The study of the microenvironment appears in this context as a promising avenue. The bone marrow microenvironment is composed of an extracellular matrix and cells, in particular mesenchymal stromal stem cells (MSC's). In adult acute leukemia, it has been clearly demonstrated that these microenvironment cells are reprogrammed by leukemia cells to allow the development and proliferation of the latter. Links have also been demonstrated in acute leukemia between the cells of the microenvironment and resistance to chemotherapy. In a certain number of cases, the support of the microenvironment for the development of leukemia or resistance to chemotherapy involves modulation of the energy metabolism of leukemia cells. This notably involves interactions between leukemic cells and MSCs and re-programming of the energy metabolism of the latter. To date, there are only very few studies concerning the role of the microenvironment in acute childhood leukemia and none to date has specifically studied the energy metabolism (oxidative phosphorylation and glycolysis) of MSCs.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Lymphoid Leukemia, Acute Myeloid Leukemia in Children
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Open-label, interventional monocentric biological study in two parallel and controlled groups
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Patients with acute leukemias
Arm Type
Active Comparator
Arm Description
Children with acute lymphoid leukemia B, acute lymphoid leukemia -T or acute myeloid leukemia
Arm Title
Control group
Arm Type
Other
Arm Description
Children without blood diseases
Intervention Type
Procedure
Intervention Name(s)
Biological sampling in patients
Intervention Description
blood and bone marrow samples from patients with Acute Leulemia.
Intervention Type
Procedure
Intervention Name(s)
Biological sampling in control patients
Intervention Description
blood and bone marrow samples from children undergoing orthopedic surgery exposing the bone marrow.(osteotomy of the pelvis).
Primary Outcome Measure Information:
Title
Oxygen Consumption Rate
Description
Difference in oxidative phosphorylation measured by OCR (Oxygen Consumption Rate) in pmol/min/nd DNA between the mesenchymal stromal stem cells (MSCs) of children with Acute Leukemia and those of children without blood diseases.
Time Frame
At inclusion
Secondary Outcome Measure Information:
Title
Difference in Extra Cellular Acidification Rate
Description
Difference in glycolysis, measured by the ECAR (Extra Cellular Acification Rate) in mpH/min/ng DNA between the MSCs of children with AL and those of children without hematological disease.
Time Frame
At inclusion
Title
Difference in Reactive Oxygen Species
Description
Difference in oxidative metabolism thanks to the measurement of reactive oxygen species (ROS), measured in MIF/isotype, between MSCs of children with AL and those of children without hematological disease
Time Frame
At inclusion
Title
Difference in doubling time in culture
Description
The difference in doubling time in culture (measured in days) between the MSCs of children with LA and those of children free of hemopathy. At each passage, the number of living and dead MSCs will be counted.
Time Frame
At inclusion
Title
Difference in Immunophenotypic profile
Description
The difference in immunophenotypic profile (cytometry, immunofluorescence) between MSCs of children with AL and those of children without hematological disease. Use of a panel of monoclonal antibodies directed against various membrane antigens (CD45, CD34, CD14, CD90, CD73, CD105).
Time Frame
At inclusion
Title
Difference in mutational profiles between MSCs and leukemia cells
Description
Difference in mutational profiles between MSCs and leukemia cells from children with AL. Comparison of mutations acquired by leukemic cells compared to stromal cells by an NGS-type high-throughput sequencing approach.
Time Frame
At inclusion
Title
Differences in transcriptomic signatures between MSCs and MSC subpopulations
Description
Differences in transcriptomic signatures between MSCs and MSC subpopulations of children with AL and those of children without hematological disease. The RNAs of the MSCs obtained after culture will be extracted then reverse-transcribed into cDNA. The quality control of the extracted RNAs will be carried out on a Bioanalyzer (Agilent). Transcriptome analysis of the MSC pool will be performed by RNA Seq/NGS. Transcriptomic identification of MSC subpopulations will be performed by single-cell RNAseq/NGS.
Time Frame
At inclusion
Title
Differences in cytokine profiles within the bone marrow
Description
Differences in cytokine profiles in the bone marrow and in the blood, measured in ng/mL, between children with AL and children without hematological disease.ELISA-like assay of IL-3, IL-6, IL-7, IL-8, IL-10, IL-15, TGF-bêta, IFN-gamma
Time Frame
At inclusion
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
15 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
for patients with AL:
Child with acute lymphoblastic or myeloblastic leukemia at diagnosis
Not having received prior hematological treatment
Aged 1 to 15 years old
Whose 2 parents, or the holder of parental authority, have signed a consent enlightened.
Affiliated patient or beneficiary of a social security scheme.
Control group patients:
Child undergoing orthopedic surgery exposing the bone marrow (osteotomy of the pelvis).
Aged between 1 and 15 years old.
Having no pathology of hematological origin.
Not having received any treatment that could interfere with the functioning of the bone marrow.
Whose 2 parents or the holder of parental authority have signed a consent enlightened.
Affiliated patient or beneficiary of a social security scheme.
Exclusion Criteria:
for patients with AL:
Patient under 1 year old and over 15 years old.
Contraindication to myelogram.
Absence of signature of the informed consent by the 2 parents or the holder of parental authority.
Patients with relapsed acute lymphoblastic or myeloblastic leukemia.
Having received prior hematological treatments.
Parents with physical or mental condition not allowing to understand the informed consent.
Control group patients
Patient under 1 year old and over 15 years old.
Having an underlying haematological pathology.
Absence of signature of the informed consent by the 2 parents or the holder of parental authority.
Having received prior hematological treatments.
Parents with physical or mental condition not allowing to understand informed consent.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Olivier HERAULT, MD-PhD
Phone
+33(0)234378902
Email
olivier.herault@univ-tours.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Wiebe de JONG, MSc
Phone
+33(0)247474680
Email
w.dejong@chu-tours.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Olivier HERAULT, MD-PhD
Organizational Affiliation
University Hospital of TOURS
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Julien LEJEUNE, MD-PhD
Organizational Affiliation
University Hospital of TOURS
Official's Role
Principal Investigator
Facility Information:
Facility Name
Service d'hématologie biologique-CHRU TOURS
City
Tours
ZIP/Postal Code
37044
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Olivier HERAULT, MD-PhD
Phone
+33(0)247474721
Email
olivier.herault@univ-tours.fr
First Name & Middle Initial & Last Name & Degree
Olivier HERAULT, MD-PhD
Facility Name
Service d'onco-hématologie pédiatrique -CHRU Tours
City
Tours
ZIP/Postal Code
37044
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Julien LEJEUNE, MD-PhD
Email
j.lejeune@chu-tours.fr
First Name & Middle Initial & Last Name & Degree
Julien LEJEUNE, MD-PhD
First Name & Middle Initial & Last Name & Degree
Emmanuel Gyan, MD-PhD
First Name & Middle Initial & Last Name & Degree
Pascale Blouin, MD
First Name & Middle Initial & Last Name & Degree
Anne Jourdain, MD
First Name & Middle Initial & Last Name & Degree
Marion Gillibert-Yvert, MD
First Name & Middle Initial & Last Name & Degree
Jill Serre, MD
First Name & Middle Initial & Last Name & Degree
Léa Bosdure, MD
Facility Name
Service de chirurgie orthopédique pédiatrique -CHRU TOURS
City
Tours
ZIP/Postal Code
37044
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Thierry ODENT, MD-PhD
Phone
+33(0)247473822
Email
t.odent@chu-tours.fr
First Name & Middle Initial & Last Name & Degree
Thierry ODENT, MD-PhD
12. IPD Sharing Statement
Plan to Share IPD
No
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Study of the Medullary Microenvironment in Acute Childhood Leukemia
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