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

NCT07514715 | Not Yet Recruiting

• 1 other identifier: RT4
• Study Type: observational
• Target: 129
• Locations: 1 country
• Sites: 30

Brief Summary

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.

Conditions

Aggressive B-cell Lymphomas

Keywords

Circulating Tumor DNA; Measurable Residual Disease; Large B-Cell Lymphoma; PhasED-Seq; PET-Scan in Lymphoma

Outcome Measures

Primary Outcomes (1)

• The primary endpoint is the proportion of participants for whom MRD results are delivered within these timelines at the predefined interim treatment response assessment.

  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 Outcomes (11)

• Survival

  at 1 year

• Progression/relapse

  at 1 year

• Evaluate the prognostic value of ctDNA/radiomics PET at mid-treatment and end-of-treatment

  at 1 year

• To document and classify the reasons for unsuccessful PET acquisition, analysis or reporting

  at interim timepoint, after Cycle 4 (each cycle is 14 or 21 days)

• To describe the clinical impact of the results on patient management

  at interim timepoint, after Cycle 4 (each cycle is 14 or 21 days) and End of treatment timepoint

Study Arms (1)

All participants will receive standard of care treatment only, according to local practice.

Other: blood test

Interventions

blood test OTHER

Three blood tests will be performed (one before treatment, one at mid treatment, and one at the end of treatment) for ctDNA analysis.

All participants will receive standard of care treatment only, according to local practice.

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants with aggressive B cell lymphoma

You may qualify if:

• Participant, or the participant's legal representative, who voluntarily understands and signs an informed consent form prior to any study specific assessment or procedure.
• Aged 12 years or older at the time of signing the informed consent form (ICF), with no upper age limit.
• 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:
• With MYC and BCL2 and/or BCL6 rearrangements (double hit/triple hit)
• Not otherwise specified (i.e., without double/triple rearrangements)
• Primary mediastinal B cell lymphoma (PMBL)
• Transformed indolent B cell lymphoma, including:
• Transformed follicular lymphoma (tFL)
• Transformed marginal zone lymphoma (tMZL)
• Transformed nodal or splenic B cell lymphomas, not otherwise specified (NOS)
• 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).
• Requiring standard first line systemic therapy with curative intent.

You may not qualify if:

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

Sponsors & Collaborators

• The Lymphoma Academic Research Organisation: lead

Study Sites (30)

CHU D'AMIENS - HOPITAL SUD - Service Hématologie Clinique et Thérapie Cellulaire

Amiens, 80054, France

Location

CHU D'ANGERS - Service des Maladies du Sang

Angers, 49033, France

Location

CH D'AVIGNON - HOPITAL HENRI DUFFAUT - Service d'Onco-Hématologie

Avignon, 84000, France

Location

CHU JEAN MINJOZ - Service Hématologie

Besançon, 25030, France

Location

CHU ESTAING - Service Thérapie Cellulaire et Hématologie Clinique

Clermont-Ferrand, 63003, France

Location

HOPITAL HENRI MONDOR - Unité Hémopathies Lymphoïdes

Créteil, 94010, France

Location

CHU DIJON BOURGOGNE - Service Hématologie Clinique

Dijon, 21000, France

Location

CHD DE VENDEE - Service Hématologie

La Roche-sur-Yon, 85925, France

Location

CHU DE GRENOBLE - Service Hématologie

La Tronche, 38700, France

Location

CH DE VERSAILLES - HOPITAL ANDRE MIGNOT - Service Hématologie Adolescents et Jeunes Adultes

Le Chesnay, 78157, France

Location

HOPITAL SAINT VINCENT-DE-PAUL - Service Hématologie Clinique

Lille, 59020, France

Location

CHU DE LILLE - HOPITAL CLAUDE HURIEZ - Service des Maladies du Sang

Lille, 59037, France

Location

CENTRE LEON BERARD - Service Hématologie

Lyon, 69373, France

Location

CHU DE MONTPELLIER - Département d'Hématologie Clinique

Montpellier, 34295, France

Location

CHU DE NANTES - Service Hématologie

Nantes, 44093, France

Location

CHU ORLEANS - Service Oncologie Médicale

Orléans, 45067, France

Location

HOPITAL COCHIN - Hématologie clinique

Paris, 75014, France

Location

HOPITAL SAINT-LOUIS - Service Hématologie Adolescents et Jeunes Adultes

Paris, 75475, France

Location

HOPITAL DE LA PITIE SALPETRIERE - Service Hématologie Clinique

Paris, 75651, France

Location

HOPITAL NECKER - Service Hématologie Adultes

Paris, 75743, France

Location

CHU DE BORDEAUX - HOPITAL HAUT-LEVEQUE - CENTRE FRANCOIS MAGENDIE - Service d'Hématologie et Thérapie Cellulaire

Pessac, 33604, France

Location

CHU LYON-SUD - Hématologie Clinique

Pierre-Bénite, 69495, France

Location

CHU DE POITIERS - HOPITAL DE LA MILETRIE - Service d'Oncologie Hématologique et Thérapie Cellulaire

Poitiers, 86021, France

Location

CHU DE REIMS - HOPITAL ROBERT DEBRE - Service Hématologie

Reims, 51092, France

Location

CHU PONTCHAILLOU - Hématologie Clinique

Rennes, 35033, France

Location

CENTRE HENRI BECQUEREL - Service Hématologie

Rouen, 76038, France

Location

INSTITUT CURIE - SITE SAINT-CLOUD - Service Hématologie

Saint-Cloud, 92210, France

Location

IUCT ONCOPOLE - Service Hématologie

Toulouse, 31059, France

Location

CHRU NANCY - HÔPITAL BRABOIS - Service Hématologie

Vandœuvre-lès-Nancy, 54511, France

Location

GUSTAVE ROUSSY CANCER CAMPUS GRAND PARIS - Département Médecine Oncologique

Villejuif, 94085, France

Location

Related Publications (6)

• Meignan M, Gallamini A, Meignan M, Gallamini A, Haioun C. Report on the First International Workshop on Interim-PET-Scan in Lymphoma. Leuk Lymphoma. 2009 Aug;50(8):1257-60. doi: 10.1080/10428190903040048.

  PMID: 19544140 BACKGROUND

• Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, Lister TA; Alliance, Australasian Leukaemia and Lymphoma Group; Eastern Cooperative Oncology Group; European Mantle Cell Lymphoma Consortium; Italian Lymphoma Foundation; European Organisation for Research; Treatment of Cancer/Dutch Hemato-Oncology Group; Grupo Espanol de Medula Osea; German High-Grade Lymphoma Study Group; German Hodgkin's Study Group; Japanese Lymphorra Study Group; Lymphoma Study Association; NCIC Clinical Trials Group; Nordic Lymphoma Study Group; Southwest Oncology Group; United Kingdom National Cancer Research Institute. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014 Sep 20;32(27):3059-68. doi: 10.1200/JCO.2013.54.8800.

  PMID: 25113753 BACKGROUND

• Wang S, Nijland M, Strobbe L, Oosterveld M, Boersma R, Koene H, Klerk C, de Jongh E, Koster A, Pruijt H, van der Poel M, van Werkhoven E, Zanders H, Dinmohamed A, Pegtel M, Meek S, Stowell SL, Warinske H, Alizadeh AA, Kurtz DM, Chamuleau MED. Prospective Validation of Circulating Tumor DNA Measurable Residual Disease After First-Line Therapy in Large B-Cell Lymphoma. J Clin Oncol. 2026 Feb 10;44(5):400-409. doi: 10.1200/JCO-25-01712. Epub 2025 Dec 12.

  PMID: 41385760 BACKGROUND

• Krupka JA, Moutsopoulos I, Cutmore NH, Trethewey CS, Dayimu A, Goodhew R, Kaji F, Raso-Barnett L, Cheow H, Elzubeir L, Smith J, Kamil A, Barbara RR, Price J, Elston K, Kolodziejczyk A, Tarantino S, Mariscotti F, Barry P, Frost S, Demiris N, Thomas MG, Hassane D, Munugalavadla V, Nagumantry SK, Karanth MJ, Ahearne M, Shah N, Fox CP, Anand S, Hodson DJ. Phased Variant-Supported Circulating Tumor DNA as a Prognostic Biomarker After First-Line Treatment in Large B-Cell Lymphoma: Findings From the DIRECT Study. J Clin Oncol. 2026 Feb 10;44(5):410-420. doi: 10.1200/JCO-25-01587. Epub 2025 Dec 22.

  PMID: 41428995 BACKGROUND

• Kurtz DM, Soo J, Co Ting Keh L, Alig S, Chabon JJ, Sworder BJ, Schultz A, Jin MC, Scherer F, Garofalo A, Macaulay CW, Hamilton EG, Chen B, Olsen M, Schroers-Martin JG, Craig AFM, Moding EJ, Esfahani MS, Liu CL, Duhrsen U, Huttmann A, Casasnovas RO, Westin JR, Roschewski M, Wilson WH, Gaidano G, Rossi D, Diehn M, Alizadeh AA. Enhanced detection of minimal residual disease by targeted sequencing of phased variants in circulating tumor DNA. Nat Biotechnol. 2021 Dec;39(12):1537-1547. doi: 10.1038/s41587-021-00981-w. Epub 2021 Jul 22.

  PMID: 34294911 BACKGROUND

• Kurtz DM, Scherer F, Jin MC, Soo J, Craig AFM, Esfahani MS, Chabon JJ, Stehr H, Liu CL, Tibshirani R, Maeda LS, Gupta NK, Khodadoust MS, Advani RH, Levy R, Newman AM, Duhrsen U, Huttmann A, Meignan M, Casasnovas RO, Westin JR, Roschewski M, Wilson WH, Gaidano G, Rossi D, Diehn M, Alizadeh AA. Circulating Tumor DNA Measurements As Early Outcome Predictors in Diffuse Large B-Cell Lymphoma. J Clin Oncol. 2018 Oct 1;36(28):2845-2853. doi: 10.1200/JCO.2018.78.5246. Epub 2018 Aug 20.

  PMID: 30125215 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

ctDNA

MeSH Terms

Conditions

Neoplasm, Residual

Interventions

Hematologic Tests

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Vincent CAMUS, Dr

  CENTRE HENRI BECQUEREL - Service Hématologie

  PRINCIPAL INVESTIGATOR

• Cédric ROSSI, Pr

  CHU DIJON BOURGOGNE - Service Hématologie Clinique

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Project Management Project Management

CONTACT

+33 (0) 4 27 01 27 22; RT4@lysarc.org

Study Design

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

Study Record Dates

• First Submitted: March 13, 2026
• First Posted: April 7, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): October 1, 2028
• Last Updated: April 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (30)