Study of NK Cells in the Monitoring of Patients With Acute Leukemia or Myelodysplasia

Official title

ENKLA-M : Study of NK Cells in the Monitoring of Patients With Acute Leukemia or Myelodysplasia

Overview

The aim of the ENKLA-M study is to collect samples from patients with acute Myeloid Leukemia (AML), Acute Lymphocytic Leukemia (ALL), and myelodysplastic syndrome (MDS) to study the evolution of blast phenotype (NK receptor ligands and adhesion molecules) and the biology of patients' NK cells). To do this, blood and bone marrow samples will be collected from patients at diagnosis in order to characterize: (I) the phenotype of ALL and AML blasts with respect to NK receptor ligands and adhesion molecules; (II) the phenotypic profile of NK cells, (III) to further characterize the NK cell repertoire dynamics over time (day 30, day 60, day 90, 6 months, and 1 year), focusing on NK cell populations identified in healthy individuals as particularly effective against leukemia, by defining their phenotypic and transcriptomic profiles; and (IV) the impact of azacitidine (AZA) and donor lymphocyte infusions (DLI) on the biology of NK cells in transplanted patients. Clinical data and KIR/HLA genetic profiles will be used to analyze all NK phenotypic and functional data, with the aim of better defining: (i) the key molecular interactions between NK cells and leukemic cells; (ii) markers of NK cell anti-leukemic efficacy during hematopoietic reconstitution; and (iii) whether AZA/DLI treatment enhances the functional potential of NK cells via KIR-HLA interaction, thereby improving their effectiveness against residual disease.

Interventions

• Other Bone marrow sampling (during routine care)
  Bone marrow sample (1 ml)
• Other Blood samples (during routine care)
  3 tubes of 10 ml per visit

Primary outcome measures

• Define the KIR and HLA genetic markers associated with an anti-leukaemic response mediated by NK cells at different stages in the progression of Acute lymphocytic leukaemia or a myalodysplasia syndrome. [Time frame: 12 months]

Secondary outcome measures (4)

• Assess the functional potential of different NK cell populations at diagnosis of acute myeloid leukaemia, acute lymphoblastic leukaemia and myelodysplastic syndrome (at each possible relapse of the patient). [Time frame: 12 months]
• Assess NK cell reconstitution during transplant of hematopoietic stem cells. [Time frame: 12 months]
• Assess the impact of the hypomethylating agent AZA used to prevent relapse after allogeneic transplantation for acute myeloid leukaemia or myelodysplastic syndrome on NK cells. [Time frame: 12 months]
• Assess the impact of Donor Lymphocyte Injection used in the prevention of post-allogeneic transplant relapse on NK cells. [Time frame: 12 months]

Eligibility criteria

Inclusion criteria

• Adult patients diagnosed with acute myeloid leukaemia (LAM), acute lymphoblastic leukaemia (LAL) or myelodysplastic syndrome (SMD).
• Adult patients receiving a HSC transplant.
• Adult patients receiving or not AZA treatment after transplantation.
• Patients who have signed a consent form.
• Patients affiliated with a social security system. EXCLUSION CRITERIA
• Minors,
• Pregnant and/or breastfeeding women
• Adult patients under guardianship,
• Protected persons.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

France · 1 center

• CHU de Nantes — Nantes

Identifiers

NCT: NCT07249476 · RC25_0333 · ANSM - IDRCB

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗