Acute Lymphoblastic Leukaemia - CategoryNCT07499336
UNDERSTANDING THE T-CELL AND B-CELL RECEPTOR REPERTOIRE IN CHILDREN AND YOUNG ADULTS WITH ANTI-DRUG ANTIBODIES AGAINST PEG ASPARAGINASE
An observational study of Acute Lymphoblastic Leukaemia - Category, run by Aarhus University Hospital.
Trial summary
The aim of this sub study is to identify biomarkers in children and young adults with Acute Lymphoblastic Leukemia with hypersensitivity to PEG-asparaginase. Evidence strongly implicates humoral immunity in Asparaginase immunogenicity with neutralizing antibodies18. Read more about this study
- Who is it for?
- Ages Up to 45 years
- Conditions the study is for
- Acute Lymphoblastic Leukaemia - Category
- What is being tested?
- Hypersensitivity reaction to asparaginase
- How many people
- 45 participants
- Where
- No sites listed yet
- Study dates
- 7 Apr 2026to 31 Jan 2030
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 45 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: 45 Children and young adults diagnosed with Acute lymphoblastic leukemia
Who may be able to join
- ALL treated with Asparaginase, either with or without hypersensitivity reaction
Who cannot join
- -
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
Birgitte Klug Albertsen, Professor contact
About this study
The aim of this sub study is to identify biomarkers in children and young adults with Acute Lymphoblastic Leukemia with hypersensitivity to PEG-asparaginase.
Evidence strongly implicates humoral immunity in Asparaginase immunogenicity with neutralizing antibodies18. Asparaginase is a bacterial enzyme not naturally present in the human body, and therefore highly immunogenic. Upon administration, antigen-presenting cells internalize and present fragments of the enzyme to naïve T cells, driving their differentiation into T-helper cells signaling differentiation of B-cells. A subset of activated B-cells matures into long-lived plasma cells that home to the bone marrow, where they continuously secrete anti-asparaginase antibodies. Others differentiate into Memory-B-cells that enable rapid antibody responses. This immunological memory means that once sensitization occurs, re-exposure to asparaginase triggers strong hypersensitivity reactions that make further treatment unsafe. Yet, despite the clinical importance, only one study exists on TCR repertoire in response to anti-asparaginase antibodies, but no studies to date have directly profiled the B-cell receptor (BCR) repertoire in children with anti-asparaginase antibodies. The BCR sequencing has recently been developed. By integrating BCR-seq from blood and BM with serum proteomics (Ig-Seq), we can directly link specific plasma cell clones to circulating anti-asparaginase antibodies. This approach will provide mechanistic insight into drug immunogenicity and enable the identification of molecular biomarkers of hypersensitivity risk in children and young adults with ALL.
Read more
Methods:
The investigators will perform a longitudinal Danish cohort study in pediatric and young adult ALL patients receiving PEG-asparaginase as part of induction and post-consolidation therapy treated on the A2G-1. The investigators will include 20 patients with hypersensitivity and 20 without. Biological samples will be collected at baseline, during early post-exposure with PEG-asparaginase, at clinical hypersensitivity, and at follow-up timepoints according to the A2G-1. The investigators will pair these samples with EDTA-plasma samples from the same timepoints. The investigators will perform enrichment of plasma cells together with bulk TCR and BCR repertoire and clonotype sequencing. From plasma the investigators will perform serum proteomics to identify peptide fragments of circulating anti-asparaginase antibodies. Ig-Seq peptides will be aligned with BCR sequences from PBMC and BM to map specific antibodies to their clonal plasma cell origin. This approach yields a direct functional link between repertoire data and pathogenic antibodies.
The investigators will compare bone marrow repertoires with blood samples to determine whether circulating clones reflect the dominant marrow-resident plasma cells. If anti-asparaginase antibodies-specific BCRs can be reliably detected in blood, this may serve as a non-invasive biomarker, reducing the need for bone marrow sampling.
- Conditions
- Acute Lymphoblastic Leukaemia - Category
- Being tested
- Hypersensitivity reaction to asparaginase
- Keywords
- ALL
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hypersensitivity reaction to asparaginaseOther
The investigators will perform a longitudinal Danish cohort study in pediatric and young adult ALL patients receiving PEG-asparaginase as part of induction and post-consolidation therapy treated on the A2G-1.
20 patients with hypersensitivity and 20 without will be included in the study. Biological samples will be collected at baseline, during early post-exposure with PEG-asparaginase, at clinical hypersensitivity, and at follow-up timepoints according to the A2G-1. Samples will be paired with EDTA-plasma samples from the same timepoints. Enrichment of plasma cells together with bulk TCR and BCR repertoire and clonotype sequencing will be performed. From plasma investigators will perform serum proteomics to identify peptide fragments of circulating AAA. Investigators will align Ig-Seq peptides with BCR sequences from PBMC and BM to map specific antibodies to clonal plasma cell origin. This approach yields a direct functional link between repertoire data and pathogenic antibodies.
What is being measured
The primary outcome is the main question the study is designed to answer.
Identify biomarkers in children and young adults with ALL with hypersensitivity to PEG-asparaginase.
Identify biomarkers in children and young adults with ALL with hypersensitivity to PEG-asparaginase.
Measured: 5 years
Identify biomarkers in children and young adults with ALL with hypersensitivity to PEG-asparaginase.
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2026
- Study start7 Apr 2026 (estimated)
- Primary completion31 Jan 2030 (estimated)
- Study completion31 Jan 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Lymphoblastic Leukaemia - CategoryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Aarhus University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Birgitte Klug Albertsen, Aarhus University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07499336
- Sponsor's protocol ID
- Asparaginase Hypersensitivity
- Status last verified
- Mar 2026
- First submitted
- 24 Mar 2026
- Last updated
- 13 Apr 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No