European Project for ctDNA Detection as a Biomarker for Non-invasive Therapy Monitoring in Paediatric Classical Hodgkin Lymphoma

NCT07356882 | Recruiting

• 2 other identifiers: APHP241626IDRCB 2025-A01092-47
• Study Type: observational
• Target: 400
• Locations: 1 country
• Sites: 1

Brief Summary

Classical Hodgkin lymphoma (cHL) accounts for 15% of all cases of cancer in children and adolescents and represents the first cause of cancer during adolescence. Combined multi-modal chemotherapy and modern radiation techniques have transformed cHL in a highly curable cancer. However, up to 10-15% of patients still experience recurrent or primary refractory disease. Thus, there is an unmet need for unravelling the underlying mechanisms of treatment failure and refractoriness in paediatric cHL. Further refinements of treatment strategy are still needed to improve treatment results both in relapse and refractory (R/R) patients and to reduce long-term morbidity and mortality treatment related. Therefore, two main objectives arise: to improve early detection of patients with a high relapse risk to potentially intensify the first line treatment and to better identify low risk patients to further reduce the treatment burden in this good-prognostic population. Initial disease stratification and long-term outcome predictions remain a challenging issue in the field. PET/CT is currently the reference imaging method for initial staging and improves detection of extra nodal disease. None of previous prognostic factors accurately identify patients who will respond adequately and therefore limit the ability to identify patients who should require treatment that is more intensive or new therapeutic approaches like immunotherapy. Taken together, these data emphasize a clear unmet need in the field of cHL. We aim to develop a biomarker tool, which could sharpen the initial risk stratification, improve the assessment of disease evaluation during the treatment and beyond and facilitate the detection of relapse. Over the past decade, as in other malignancies the potential of quantification of circulating tumour DNA (ctDNA) or liquid biopsy, in circulating cell-free DNA (cfDNA) that comprises DNA fragments released from apoptotic or necrotic cells into circulation, has emerged as a promising tool for diagnosis and exploration of the genetic landscape associated with HRS and for response evaluation. Experiences of ctDNA in cHL was first reported in adult cHL. These previous studies paved the way for ctDNA implementation in cHL. First, they contributed to confirm the feasibility to use ctDNA in the detection of tumor-associated mutation. Using paired samples of ctDNA and tumor DNA from HRS cells obtained by microdissection they confirmed the consistent correlation between these two methods. Second, they highlighted the potential role of ctDNA as a surrogate marker for tumor baseline assessment and more importantly for interim evaluation reporting an excellent correlation between the PET/CT result and the presence or the absence of ctDNA after 2 cycles of chemotherapy. Furthermore, Sobesky et al. previously reported that cured patients who were inconsistently judged as interim PET/CT-positive had a more than 2-log drop in ctDNA, whereas relapsing patients who were inconsistently judged as interim PET/CT negative had a less than 2-log drop in ctDNA. These data suggest that ctDNA could be a relevant adjunct to conventional PET/CT approach.

Conditions

Classical Hodgkin Lymphoma

Keywords

Classical Hodgkin lymphoma; Pediatric oncology; Circulating tumor DNA (ctDNA); Liquid biopsy; Risk stratification; Minimal residual disease (MRD); Biomarker; Next-Generation Sequencing (NGS); Treatment response evaluation; Relapse prediction; PET/CT correlation

Outcome Measures

Primary Outcomes (1)

• Relapse-Free Survival (RFS) at 2 and 5 years based on ctDNA status at diagnosis

  Time from initial diagnosis to first relapse or death from any cause. Patients will be stratified by ctDNA status at diagnosis, including quantitative burden and mutation profiles.

  2 years and 5 years

Secondary Outcomes (4)

• Diagnostic performance of ctDNA after 1 cycle of chemotherapy

  At Day 28 (post first OEPA cycle)

• Diagnostic performance of ctDNA after 2 cycles of chemotherapy

  At Day 56 (post second OEPA cycle)

• Diagnostic performance of ctDNA at end of treatment

  At treatment completion (approximately Month 6)

• Molecular landscape of ctDNA at relapse

  Up to 5 years

Study Arms (1)

Main Cohort

ctDNA analysis at 4 timepoints during standard treatment

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Children and adolescents newly diagnosed with Hodgkin lymphoma treated in participating pediatric oncology centers. Patients will be enrolled at diagnosis and followed prospectively for relapse outcomes

You may qualify if:

• Confirmed classical Hodgkin lymphoma (cHL)
• Children and young adults under the age of 25 years old
• Signature of informed consent by the patient and/or holders of parental authority (depending on the age of the patient)
• Affiliation to a social security scheme or being beneficiary of such a scheme

You may not qualify if:

• Previous treatment with chemotherapy or radiotherapy for another cancer
• Pretreatment of Hodgkin lymphoma (except one treatment with corticosteroid for 7 to 10 days for large or compressive mediastinal tumors).
• Diagnosis of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL)
• Other concomitant malignancies • Residence outside participating countries in for which long-term follow-up cannot be ensured

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Centre de Lutte contre le Cancer Henri Becquerel, Rouen, France: collaborator
• University Medical Center of Giessen, Germany: collaborator

Study Sites (1)

Pediatric Hematology and Oncology Department

Paris, 75012, France

RECRUITING

MeSH Terms

Conditions

Neoplasm, Residual

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Mathieu SIMONIN, MD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mathieu SIMONIN, Medical Doctor

CONTACT

00 33 1 44 73 66 04; mathieu.simonin@aphp.fr

Fabrice JARDIN, Professor

CONTACT

+ 33 1 49 28 23 06; fabrice.jardin@chb.unicancer.fr

Study Design

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

Study Record Dates

• First Submitted: January 13, 2026
• First Posted: January 21, 2026
• Study Start: November 24, 2025
• Primary Completion (Estimated): November 1, 2029
• Study Completion (Estimated): November 1, 2029
• Last Updated: January 21, 2026

Record last verified: 2026-01

Locations

FR (1)