Proof of Concept for Real-time Multicentric Monitoring of MRD by PET and ctDNA in Aggressive B-Cell Lymphomas (RT4)

April 7, 2026 updated by: The Lymphoma Academic Research Organisation

Proof of Concept for Real-time Multicentric Monitoring of Minimal Residual Disease (MRD) by PET and Circulating Tumor DNA (ctDNA) in Aggressive B-Cell Lymphomas

RT4 (REAL TIME TAILORED THERAPY) study was designed as a national, multicenter proof of concept aiming to demonstrate the technical and operational capacity of the French Connect network and the Positron Emission Tomography (PET) review network to ensure, within a coordinated framework, real time MINIMAL RESIDUAL DISEASE (MRD) monitoring through ctDNA analysis and centralized review of PET imaging.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Monitoring measurable residual disease (MRD) through the analysis of circulating tumor DNA (ctDNA) in plasma is rapidly emerging as one of the major recent advances in the management of lymphomas. Over the past years, several studies have shown that ctDNA enables a dynamic and highly sensitive assessment of treatment response, surpassing the limitations of conventional approaches based on imaging only.

Importantly, these advances do not replace or diminish the role of PET imaging. On the contrary, metabolic imaging and molecular monitoring are increasingly seen as complementary tools. When used together, PET imaging and ctDNA kinetic analysis may dynamically refine risk stratification and enable truly individualized adaptive treatment strategies. However, this synergy between MRD and PET can only influence clinical practice or trial design if results are available throughout patient management within a timeframe compatible with therapeutic decision making.

Study Type

Observational

Enrollment (Estimated)

129

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Project Management Project Management
  • Phone Number: +33 (0) 4 27 01 27 22
  • Email: RT4@lysarc.org

Study Locations

  • France
      • Amiens, France, 80054
        • CHU D'AMIENS - HOPITAL SUD - Service Hématologie Clinique et Thérapie Cellulaire
        • Contact:
      • Angers, France, 49033
        • CHU D'ANGERS - Service des Maladies du Sang
        • Contact:
      • Avignon, France, 84000
        • CH D'AVIGNON - HOPITAL HENRI DUFFAUT - Service d'Onco-Hématologie
        • Contact:
      • Besançon, France, 25030
        • CHU JEAN MINJOZ - Service Hématologie
        • Contact:
      • Clermont-Ferrand, France, 63003
        • CHU ESTAING - Service Thérapie Cellulaire et Hématologie Clinique
        • Contact:
      • Créteil, France, 94010
        • HOPITAL HENRI MONDOR - Unité Hémopathies Lymphoïdes
        • Contact:
      • Dijon, France, 21000
        • CHU DIJON BOURGOGNE - Service Hématologie Clinique
        • Contact:
      • La Roche-sur-Yon, France, 85925
        • CHD DE VENDEE - Service Hématologie
        • Contact:
      • La Tronche, France, 38700
        • CHU DE GRENOBLE - Service Hématologie
        • Contact:
      • Le Chesnay, France, 78157
        • CH DE VERSAILLES - HOPITAL ANDRE MIGNOT - Service Hématologie Adolescents et Jeunes Adultes
        • Contact:
      • Lille, France, 59020
        • HOPITAL SAINT VINCENT-DE-PAUL - Service Hématologie Clinique
        • Contact:
      • Lille, France, 59037
        • CHU DE LILLE - HOPITAL CLAUDE HURIEZ - Service des Maladies du Sang
        • Contact:
      • Lyon, France, 69373
      • Montpellier, France, 34295
        • CHU DE MONTPELLIER - Département d'Hématologie Clinique
        • Contact:
      • Nantes, France, 44093
      • Orléans, France, 45067
      • Paris, France, 75014
        • HOPITAL COCHIN - Hématologie clinique
        • Contact:
      • Paris, France, 75475
        • HOPITAL SAINT-LOUIS - Service Hématologie Adolescents et Jeunes Adultes
        • Contact:
      • Paris, France, 75651
        • HOPITAL DE LA PITIE SALPETRIERE - Service Hématologie Clinique
        • Contact:
      • Paris, France, 75743
        • HOPITAL NECKER - Service Hématologie Adultes
        • Contact:
      • Pessac, France, 33604
        • CHU DE BORDEAUX - HOPITAL HAUT-LEVEQUE - CENTRE FRANCOIS MAGENDIE - Service d'Hématologie et Thérapie Cellulaire
        • Contact:
      • Pierre-Bénite, France, 69495
        • CHU LYON-SUD - Hématologie Clinique
        • Contact:
      • Poitiers, France, 86021
        • CHU DE POITIERS - HOPITAL DE LA MILETRIE - Service d'Oncologie Hématologique et Thérapie Cellulaire
        • Contact:
      • Reims, France, 51092
        • CHU DE REIMS - HOPITAL ROBERT DEBRE - Service Hématologie
        • Contact:
      • Rennes, France, 35033
        • CHU PONTCHAILLOU - Hématologie Clinique
        • Contact:
      • Rouen, France, 76038
      • Saint-Cloud, France, 92210
        • INSTITUT CURIE - SITE SAINT-CLOUD - Service Hématologie
        • Contact:
      • Toulouse, France, 31059
      • Vandœuvre-lès-Nancy, France, 54511
        • CHRU NANCY - HÔPITAL BRABOIS - Service Hématologie
        • Contact:
      • Villejuif, France, 94085
        • GUSTAVE ROUSSY CANCER CAMPUS GRAND PARIS - Département Médecine Oncologique
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Participants with aggressive B cell lymphoma

Description

Inclusion Criteria:

  1. Participant, or the participant's legal representative, who voluntarily understands and signs an informed consent form prior to any study specific assessment or procedure.
  2. Aged 12 years or older at the time of signing the informed consent form (ICF), with no upper age limit.

  3. Histologically confirmed diagnosis, according to the 2022 WHO classification, of one of the following lymphomas:

    Aggressive B cell lymphoma, including:

    • Diffuse large B cell lymphoma, not otherwise specified (DLBCL NOS)

    • High grade B cell lymphoma (HGBCL), including:

      1. With MYC and BCL2 and/or BCL6 rearrangements (double hit/triple hit)
      2. Not otherwise specified (i.e., without double/triple rearrangements)
    • Primary mediastinal B cell lymphoma (PMBL)

    • Transformed indolent B cell lymphoma, including:

      1. Transformed follicular lymphoma (tFL)
      2. Transformed marginal zone lymphoma (tMZL)
      3. Transformed nodal or splenic B cell lymphomas, not otherwise specified (NOS)
  4. Presence of measurable disease on pre treatment PET imaging, defined as at least one nodal lesion measurable in two dimensions, > 1.5 cm in its largest dimension (and FDG avid), or at least one extranodal lesion measurable in two dimensions, > 1.0 cm in its largest dimension (and FDG avid).
  5. Requiring standard first line systemic therapy with curative intent.
  6. Covered by a social security or health insurance system.
  7. Able to speak and understand one of the official languages of the country, unless local regulations allow the use of independent interpreters.

Exclusion Criteria:

  1. Prior systemic anticancer treatment for the current lymphoma before study inclusion. All participants must be treatment naïve for the current lymphoma.

    Note: Short term corticosteroid use (e.g., for symptom control or during diagnostic workup) is permitted before inclusion and does not constitute an exclusion criterion.

  2. Lymphomas arising in immunoprivileged sites (e.g., primary central nervous system lymphoma, primary testicular lymphoma, primary vitreoretinal lymphoma).
  3. Absence of the mandatory blood sample for circulating tumor DNA (ctDNA) analysis during screening (pre treatment blood sample).
  4. Absence of a pre treatment 18F FDG PET scan performed within ≤ 2 months prior to signing the informed consent form (mandatory PET imaging requirement).
  5. Pregnant, breastfeeding, or intending to become pregnant women of childbearing potential.
  6. Any significant medical condition, laboratory abnormality, or psychiatric disorder that may interfere with participation in this clinical study (as judged by the investigator).
  7. Individuals deprived of liberty by judicial or administrative decision.
  8. Individuals hospitalized without their consent.
  9. Adults under legal protection.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
All participants will receive standard of care treatment only, according to local practice.
Other: blood test
Three blood tests will be performed (one before treatment, one at mid treatment, and one at the end of treatment) for ctDNA analysis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The primary endpoint is the proportion of participants for whom MRD results are delivered within these timelines at the predefined interim treatment response assessment.
Time Frame: at interim timepoint, after Cycle 4 (each cycle is 14 or 21 days)

The primary objective of the study is to assess the feasibility of providing investigators with MRD results for participants with previously untreated aggressive B cell lymphomas at the time of the predefined interim response assessment, within strict timelines:

  • no more than 14 calendar days from blood collection for ctDNA results, and
  • no more than 7 calendar days after the imaging examination for the centralized PET review results.
at interim timepoint, after Cycle 4 (each cycle is 14 or 21 days)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Survival
Time Frame: at 1 year
Event Free Survival (EFS) by histology subtype
at 1 year
Progression/relapse
Time Frame: at 1 year
Duration of response (DoR) as defined by Lugano 2014 criteria
at 1 year
Evaluate the prognostic value of ctDNA/radiomics PET at mid-treatment and end-of-treatment
Time Frame: at 1 year

PFS according to ctDNA MRD status at the interim assessment and at the end of treatment assessment (positive vs negative), according to the interim PET response (response per Lugano 2014 and other radiomic parameters), and according to their combination (ctDNA + PET).

One year PFS according to baseline ctDNA concentration
at 1 year
Survival
Time Frame: 1year
Progression-free survival (PFS) by histology subtype
1year
Survival
Time Frame: 1year
Overall Survival (OS) by histology subtype
1year
Evaluate the prognostic value of ctDNA/radiomics PET at mid-treatment and end-of-treatment
Time Frame: at 1 year
EFS according to ctDNA MRD status at the interim assessment and at the end of treatment assessment (positive vs negative), according to the interim PET response (response per Lugano 2014 and other radiomic parameters), and according to their combination (ctDNA + PET).
at 1 year
Evaluate the prognostic value of ctDNA/radiomics PET at mid-treatment and end-of-treatment
Time Frame: at 1 year
OS according to ctDNA MRD status at the interim assessment and at the end of treatment assessment (positive vs negative), according to the interim PET response (response per Lugano 2014 and other radiomic parameters), and according to their combination (ctDNA + PET).
at 1 year
Number of participants with concordant results (positive PET and ctDNA or negative PET and ctDNA) and number of participants with discordant results (positive PET and negative ctDNA or negative PET and positive ctDNA).
Time Frame: Each timepoint (pre-treatment, interim timepoint, end of treatment)
Concordance rate between metabolic PET response and ctDNA result
Each timepoint (pre-treatment, interim timepoint, end of treatment)
To document and classify the reasons for unsuccessful PET acquisition, analysis or reporting
Time Frame: at interim timepoint, after Cycle 4 (each cycle is 14 or 21 days)
Number of participants with delayed results, and reasons associated.
at interim timepoint, after Cycle 4 (each cycle is 14 or 21 days)
To describe the clinical impact of the results on patient management
Time Frame: at interim timepoint, after Cycle 4 (each cycle is 14 or 21 days) and End of treatment timepoint
Number of participants with therapeutic adaptations, and associated changes.
at interim timepoint, after Cycle 4 (each cycle is 14 or 21 days) and End of treatment timepoint
To document and classify the reasons for unsuccessful ctDNA sampling, processing or result reporting.
Time Frame: at interim timepoint, after Cycle 4 (each cycle is 14 or 21 days)
Number of participants with delayed results, and reasons associated.
at interim timepoint, after Cycle 4 (each cycle is 14 or 21 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The Lymphoma Academic Research Organisation

Investigators

  • Principal Investigator: Vincent CAMUS, Dr, CENTRE HENRI BECQUEREL - Service Hématologie
  • Principal Investigator: Cédric ROSSI, Pr, CHU DIJON BOURGOGNE - Service Hématologie Clinique

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 1, 2026

Primary Completion (Estimated)

October 1, 2028

Study Completion (Estimated)

October 1, 2028

Study Registration Dates

First Submitted

March 13, 2026

First Submitted That Met QC Criteria

April 1, 2026

First Posted (Actual)

April 7, 2026

Study Record Updates

Last Update Posted (Actual)

April 13, 2026

Last Update Submitted That Met QC Criteria

April 7, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RT4

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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