Clinical trial NCT05792007: Study of the Medullary Microenvironment in Acute Childhood Leukemia
Official title: Etude du Microenvironnement médullaire Dans Les Leucémies Aiguës de l'Enfant
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Acute Lymphoid Leukemia
Acute Myeloid Leukemia in Children
Lead sponsor: University Hospital, Tours
Sponsor class: OTHER
First posted: 2023-03-30
Enrollment: 40
Sex: ALL
Minimum age (years): 1
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Open-label, interventional monocentric biological study in two parallel and controlled groups
Primary purpose: DIAGNOSTIC

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Oxygen Consumption Rate
timeFrame: At inclusion
Secondary outcomes:
measure: Difference in Extra Cellular Acidification Rate
timeFrame: At inclusion
measure: Difference in Reactive Oxygen Species
timeFrame: At inclusion
measure: Difference in doubling time in culture
timeFrame: At inclusion
measure: Difference in Immunophenotypic profile
timeFrame: At inclusion
measure: Difference in mutational profiles between MSCs and leukemia cells
timeFrame: At inclusion
measure: Differences in transcriptomic signatures between MSCs and MSC subpopulations
timeFrame: At inclusion
measure: Differences in cytokine profiles within the bone marrow
timeFrame: At inclusion
Other outcomes:
Locations:
city: Tours
country: France
facility: Service d'hématologie biologique-CHRU TOURS
city: Tours
country: France
facility: Service d'onco-hématologie pédiatrique -CHRU Tours
city: Tours
country: France
facility: Service de chirurgie orthopédique pédiatrique -CHRU TOURS
Study officials:
affiliation: University Hospital of TOURS
name: Olivier HERAULT, MD-PhD
role: STUDY_DIRECTOR
affiliation: University Hospital of TOURS
name: Julien LEJEUNE, MD-PhD
role: PRINCIPAL_INVESTIGATOR
References: