Role of T Lymphocytes in Hypersensitivity Reactions to Asparaginase in Patients Treated for Acute Lymphoblastic Leukemia.

Official title

Role of T Lymphocytes in Hypersensitivity Reactions to Asparaginase in Patients Treated for Acute Lymphoblastic Leukemia. ASTRA - Asparaginase T Cell Response Analysis

Overview

Acute lymphoblastic leukemia is a type of blood cancer that primarily affects children. Fortunately, current treatments are highly effective. One of the key drugs used is asparaginase, which works by depriving leukemic cells of a substance that is essential for their survival. However, asparaginase can also cause adverse effects, including severe allergic reactions in some patients. These reactions may be related to specific genetic factors and/or individual differences in immune responses. The aim of this research project is to better understand why certain patients develop poor tolerance to asparaginase. To achieve this, the investigators plan to collect blood cells from patients during treatment and then re-expose these cells to the drug in the laboratory. the investigators will assess whether specific immune cells-particularly T lymphocytes-become abnormally activated, which could help explain hypersensitivity reactions. Ultimately, our goal is to develop a biological assay capable of predicting which patients are at increased risk of reacting adversely to asparaginase, so that they can be offered a more tailored and safer treatment strategy.

Interventions

• Drug Asparaginase-induced in vitro T-cell stimulation
  Flow cytometric analysis of asparaginase-specific T-cell activation, compared with an unstimulated control condition and a non-antigen-dependent (polyclonal) stimulation condition. Comparison of asparaginase-specific T-cell activation between patients who developed a clinical reaction to asparaginase and patients who did not.

Primary outcome measures

• Percentage of T lymphocytes producing IFN-γ in response to asparaginase stimulation, compared with background (unstimulated) levels and the maximal response induced by PMA/ionomycin within the same patient. [Time frame: At inclusion (baseline) day 1]

Eligibility criteria

Inclusion criteria

• Confirmed diagnosis of B- or T-lineage acute lymphoblastic leukemia (ALL) according to current morphological, immunophenotypic, and molecular criteria.
• Treatment according to a standard therapeutic protocol including administration of asparaginase (PEG-asparaginase or native E. coli asparaginase).
• Age ≥ 1 year.
• Inclusion prior to the consolidation phase (sampling scheduled between induction and consolidation).

Exclusion criteria

• Prior hematopoietic stem cell transplantation (HSCT).
• Trisomy 21 (Down syndrome), due to distinct immunological features and potentially different tolerance to asparaginase.
• Emergency situation or clinical context not allowing appropriate patient information and informed consent.

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

Healthy volunteers: Yes

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Prevention

Study locations

France · 2 centers

• CHU de Nice — Nice
• APHM — Marseille

Identifiers

NCT: NCT07529223 · 25-AOIP-03 · IDRCB

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗