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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05792007
Other study ID # DR220254-MILA
Secondary ID 2022-A02570-43
Status Recruiting
Phase N/A
First received
Last updated
Start date October 26, 2023
Est. completion date October 24, 2028

Study information

Verified date November 2023
Source University Hospital, Tours
Contact Olivier HERAULT, MD-PhD
Phone +33(0)234378902
Email olivier.herault@univ-tours.fr
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 40
Est. completion date October 24, 2028
Est. primary completion date October 25, 2026
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 1 Year to 15 Years
Eligibility Inclusion Criteria: - for patients with AL: 1. Child with acute lymphoblastic or myeloblastic leukemia at diagnosis 2. Not having received prior hematological treatment 3. Aged 1 to 15 years old 4. Whose 2 parents, or the holder of parental authority, have signed a consent enlightened. 5. Affiliated patient or beneficiary of a social security scheme. - Control group patients: 1. Child undergoing orthopedic surgery exposing the bone marrow (osteotomy of the pelvis). 2. Aged between 1 and 15 years old. 3. Having no pathology of hematological origin. 4. Not having received any treatment that could interfere with the functioning of the bone marrow. 5. Whose 2 parents or the holder of parental authority have signed a consent enlightened. 6. Affiliated patient or beneficiary of a social security scheme. Exclusion Criteria: - for patients with AL: 1. Patient under 1 year old and over 15 years old. 2. Contraindication to myelogram. 3. Absence of signature of the informed consent by the 2 parents or the holder of parental authority. 4. Patients with relapsed acute lymphoblastic or myeloblastic leukemia. 5. Having received prior hematological treatments. 6. Parents with physical or mental condition not allowing to understand the informed consent. - Control group patients 1. Patient under 1 year old and over 15 years old. 2. Having an underlying haematological pathology. 3. Absence of signature of the informed consent by the 2 parents or the holder of parental authority. 4. Having received prior hematological treatments. 5. Parents with physical or mental condition not allowing to understand informed consent.

Study Design


Related Conditions & MeSH terms


Intervention

Procedure:
Biological sampling in patients
blood and bone marrow samples from patients with Acute Leulemia.
Biological sampling in control patients
blood and bone marrow samples from children undergoing orthopedic surgery exposing the bone marrow.(osteotomy of the pelvis).

Locations

Country Name City State
France Service d'hématologie biologique-CHRU TOURS Tours
France Service d'onco-hématologie pédiatrique -CHRU Tours Tours
France Service de chirurgie orthopédique pédiatrique -CHRU TOURS Tours

Sponsors (1)

Lead Sponsor Collaborator
University Hospital, Tours

Country where clinical trial is conducted

France, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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. At inclusion
Secondary 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. At inclusion
Secondary 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 At inclusion
Secondary 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. At inclusion
Secondary 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). At inclusion
Secondary 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. At inclusion
Secondary 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. At inclusion
Secondary 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-bĂȘta, IFN-gamma At inclusion
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