Study of Cell-free DNA in Children and Adolescents With Acute Lymphoblastic Leukemia

NCT07483476 | Not Yet Recruiting

• 1 other identifier: 2025-A01461-48
• Study Type: observational
• Target: 205
• Locations: 0 countries
• Sites: N/A

Brief Summary

Minimal residual disease (MRD) monitoring is a key prognostic factor in pediatric acute lymphoblastic leukemia (ALL). Currently, MRD assessment relies mainly on cellular DNA obtained from bone marrow aspirates. Although highly informative, this approach has limitations, including the need for invasive procedures and the fact that it reflects only the bone marrow compartment. Tumor cells release fragments of genomic DNA into the bloodstream, known as circulating cell-free DNA (cfDNA). In solid tumors, cfDNA analysis has emerged as a valuable non-invasive biomarker for disease monitoring and treatment response. Recent studies have shown that cfDNA is detectable in pediatric ALL. This study aims to investigate whether plasma cfDNA analysis could represent an alternative or complementary approach to bone marrow-based MRD assessment. cfDNA may better reflect the global tumor burden across the entire body and allow more frequent longitudinal monitoring during treatment. The primary objective is to assess the correlation between MRD measured in plasma cfDNA and MRD measured in bone marrow cellular DNA at two key timepoints of treatment: the end of induction (Day 29) and the end of consolidation (Day 71-78). Secondary objectives include evaluating the correlation between peripheral blood cellular DNA and bone marrow MRD, describing clonal evolution using cfDNA throughout treatment and follow-up, exploring the concordance of genomic alterations detected in cfDNA and other biological compartments, assessing the prognostic value of cfDNA MRD for relapse risk and event-free survival, and characterizing cfDNA fragmentome and methylome signatures in patients compared with healthy controls. The study will include children and adolescents with newly diagnosed ALL treated at two AP-HP pediatric hematology centers, as well as a control cohort of healthy children undergoing HLA typing for sibling stem cell transplant.

Conditions

Acute Lymphoblastic Leukemia ALL

Keywords

Pediatric acute lymphoblastic leukemia; Minimal residual disease; Cell-free DNA; Liquid biopsy; Fragmentomics; Methylome; Clonal evolution

Outcome Measures

Primary Outcomes (1)

• Correlation between plasma cfDNA MRD and bone marrow MRD

  Pearson correlation coefficient between minimal residual disease (MRD) measured in plasma circulating cell-free DNA and MRD measured in bone marrow cellular DNA. Analyses will be performed according to the type of molecular target used for MRD detection (IG/TCR rearrangements, genomic breakpoints, or pathogenic variants). End of induction (Day 29) and end of consolidation (Day 71-78)

  Up to day 78 (end of consolidation)

Secondary Outcomes (13)

• Correlation between peripheral blood cellular DNA MRD and bone marrow MRD

  At day 29

• Correlation between peripheral blood cellular DNA MRD and bone marrow MRD

  At day 78

• Clonal evolution detected in cell-free DNA

  At day 1

• Clonal evolution detected in cell-free DNA

  At day 4

• Clonal evolution detected in cell-free DNA

  At day 8

Study Arms (2)

ALL patients

Children and adolescents (\<18 years) with newly diagnosed B-cell or T-cell acute lymphoblastic leukemia without BCR::ABL1 rearrangement (and without KMT2A rearrangement in infants), included before initiation of steroid therapy or chemotherapy.

Other: Biological sample collection

Healthy control participants

Children and adolescents (\<18 years) undergoing blood sampling for HLA typing for a sibling with leukemia.

Other: Biological sample collection

Interventions

Biological sample collection OTHER

Additional peripheral blood samples will be collected during treatment and follow-up for cell-free DNA analysis. Residual samples from bone marrow and cerebrospinal fluid collected as part of standard clinical care will also be analyzed.

ALL patients; Healthy control participants

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Study population Children and adolescents with newly diagnosed acute lymphoblastic leukemia treated in participating pediatric hematology centers, as well as healthy pediatric siblings undergoing HLA typing.

You may qualify if:

• ALL population
• Age \< 18 years
• Newly diagnosed B-cell or T-cell acute lymphoblastic leukemia
• Absence of BCR::ABL1 rearrangement
• For infants (\<12 months), absence of KMT2A rearrangement
• Written informed consent from legal guardians
• Affiliation to a national health insurance system Control population
• Age \< 18 years
• Undergoing blood sampling for HLA typing in the context of bone marrow donor evaluation
• Sibling of a patient with leukemia
• Written informed consent from legal guardians
• Affiliation to a national health insurance system

You may not qualify if:

• Pregnant or breastfeeding patients
• Patients not affiliated with a health insurance system

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Biospecimen

Retention: SAMPLES WITHOUT DNA

Additional peripheral blood samples will be collected during treatment and follow-up for cell-free DNA analysis Residual samples from bone marrow and cerebrospinal fluid collected as part of standard clinical care

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Neoplasm, Residual

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Marion Strullu, MD PhD

CONTACT

+330140035388; marion.strullu@aphp.fr

Jérôme Lambert, MD PhD

CONTACT

+330142499742; jerome.lambert@u-paris.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2026
• First Posted: March 19, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): April 1, 2034
• Last Updated: March 19, 2026

Record last verified: 2026-03