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

Etude de l'ADN Libre Circulant Dans Les leucémies Aigues Lymphoblastiques de l'Enfant et de l'Adolescent

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Lymphoblastic Leukemia ALL
• Intervention / Treatment: Other: Biological sample collection

• Study Type: Observational
• Enrollment (Estimated): 205

Contacts and Locations

• Study Contact: Name: Marion Strullu, MD PhD; Phone Number: +33 +330140035388; Email: marion.strullu@aphp.fr
• Study Contact Backup: Name: Jérôme Lambert, MD PhD; Phone Number: +33 +330142499742; Email: jerome.lambert@u-paris.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: Yes

• 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.

Description

Inclusion Criteria:

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
• Inclusion before initiation of corticosteroid therapy or chemotherapy
• 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

Exclusion Criteria:

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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; 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.
Healthy control participants; Children and adolescents (<18 years) undergoing blood sampling for HLA typing for a sibling with leukemia.	Other: Biological sample collection; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between peripheral blood cellular DNA MRD and bone marrow MRD	Pearson correlation coefficient between MRD measured in peripheral blood cellular DNA and MRD measured in bone marrow cellular DNA.	At day 29
Correlation between peripheral blood cellular DNA MRD and bone marrow MRD	Pearson correlation coefficient between MRD measured in peripheral blood cellular DNA and MRD measured in bone marrow cellular DNA. At day 71 to 78	At day 78
Clonal evolution detected in cell-free DNA	Mutation profiles of cfDNA across multiple timepoints during treatment and follow-up	At day 1
Clonal evolution detected in cell-free DNA	Mutation profiles of cfDNA across multiple timepoints during treatment and follow-up	At day 4
Clonal evolution detected in cell-free DNA	Mutation profiles of cfDNA across multiple timepoints during treatment and follow-up	At day 8
Clonal evolution detected in cell-free DNA	Mutation profiles of cfDNA across multiple timepoints during treatment and follow-up	At day 15
Clonal evolution detected in cell-free DNA	Mutation profiles of cfDNA across multiple timepoints during treatment and follow-up	At day 29
Clonal evolution detected in cell-free DNA	Mutation profiles of cfDNA across multiple timepoints during treatment and follow-up At day 71 to 78	At day 78
Clonal evolution detected in cell-free DNA	Mutation profiles of cfDNA across multiple timepoints during treatment and follow-up	At end of maintenance
Clonal evolution detected in cell-free DNA	Mutation profiles of cfDNA across multiple timepoints during treatment and follow-up	3 years after remission
Concordance of genomic alterations between cfDNA and other biological compartments	Qualitative and quantitative comparison of genomic alterations detected at diagnosis in cfDNA and in other sample types (bone marrow, cerebrospinal fluid, and other tissues if available)	At diagnosis
Prognostic value of cfDNA MRD	Association between cfDNA MRD levels and relapse-free survival and event-free survival	Up to 5 years of follow-up
Fragmentome and methylome profiles of circulating DNA	Characterization and comparison of cfDNA fragment size patterns and methylation signatures between patients and healthy controls at diagnosis and during treatment. At baseline and during treatment	Up to 5 years

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): April 1, 2034

Study Registration Dates

• First Submitted: March 16, 2026
• First Submitted That Met QC Criteria: March 16, 2026
• First Posted (Actual): March 19, 2026

Study Record Updates

• Last Update Posted (Actual): March 19, 2026
• Last Update Submitted That Met QC Criteria: March 16, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Liquid biopsy; Cell-free DNA; Minimal residual disease; Clonal evolution; Methylome; Fragmentomics; Pediatric acute lymphoblastic leukemia
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Neoplastic Processes; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, Lymphoid; Leukemia; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Neoplasm, Residual; Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Other Study ID Numbers: 2025-A01461-48

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No