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Aggressive B-cell LymphomasRT4NCT07514715

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

An observational study of Aggressive B-cell Lymphomas, run by The Lymphoma Academic Research Organisation at 30 sites in France.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Aggressive B-cell Lymphomas
What is being tested?
blood test
How many people
129 participants
Where
30 sitesFrance
Study dates
30 Jun 2026to 1 Oct 2028
Phase
Observational
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Study population: Participants with aggressive B cell lymphoma

Who may be able to join

  • Participants must meet all of the following criteria to be included in the study:
  • Participant who understands and voluntarily signs an informed consent form prior to any study-specific assessment or procedure.
  • Age 18 or older at the time of signing the Informed Consent Form (ICF)
  • Histologically confirmed diagnosis, according to the WHO 2022 classification, of any of the following lymphomas:
  • Aggressive B-cell lymphoma, including:
  • Diffuse large B-cell lymphoma, unspecified (DLBCL not specified)
Show all 29Show fewer
  • High-grade B-cell lymphoma (LBHG), including:
  • With rearrangements of the MYC and BCL2 and/or BCL6 genes (double/triple hit)
  • Unspecified (i.e., no double/triple rearrangement)
  • Primary B-cell lymphoma of the mediastinum (PMBL)
  • Transformed indolent B-cell lymphoma, including:
  • Transformed follicular lymphoma (LFt)
  • Transformed marginal zone lymphoma (t-MZL)
  • Transformed, unspecified nodal or splenic B-cell lymphomas (NOS)
  • Presence of a measurable disease on pre-therapeutic PET imaging, defined as at least one two-dimensional measurable nodal lesion, defined as > 1.5 cm in its largest dimension (and FDG-greedy lesion), or at least one two-dimensional measurable extranodal lesion, defined as > 1.0 cm in its largest dimension (and FDG-hungry lesion).
  • Requiring standard first-line systemic treatment with curative intent
  • Person covered by a social security scheme
  • Person able to understand and speak French. Exclusion criteria
  • Participants who meet any of the criteria below will not be eligible for inclusion / should be excluded from the study:
  • Systemic anticancer treatment of current lymphoma prior to inclusion in the study. All participants must be previously untreated for current lymphoma.
  • Note: Short-term corticosteroid therapy (e.g., for symptom control or as part of diagnostic workup) is allowed prior to inclusion and is not an exclusion criterion.
  • Lymphomas associated with an immuno-privileged site (e.g., primary central nervous system lymphoma, primary testicular lymphoma, primary vitreoretinal lymphoma).
  • Absence of mandatory blood sampling for the analysis of circulating tumor DNA (ctDNA) during screening (pre-therapeutic sampling).
  • Absence of 18F-FDG PET examination performed within 2 months ≤ the date of signing the consent (mandatory pre-therapeutic PET imaging).
  • Pregnant, intending to be pregnant, or breastfeeding woman of childbearing potential
  • Any significant medical condition, laboratory abnormality, or psychiatric illness that may interfere with participation in this clinical study (in the opinion of the investigator)
  • Person deprived of liberty by judicial or administrative decision
  • Person hospitalized without their consent
  • Adult under legal protection

Who cannot join

None listed.

Trial locations and contacts

30 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Project Management Project Management contact

+33 (0) 4 27 01 27 22

RT4@lysarc.org

30 sites in 1 country

France30 sites

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

    Amiens, 80054

    Dr. Caroline SKRZYPCZAK, +33 (0)3 22 45 59 14, skrzypczak.caroline@chu-amiens.fr

  • CHU D'ANGERS - Service des Maladies du Sang

    Angers, 49033

    Dr. Jérôme PAILLASSA, +33 (0)6 21 82 31 85, jerome.paillassa@chu-angers.fr

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

    Avignon, 84000

    Dr. Thierry TAKAM, +33 (0)4 32 75 93 78, takam.thierry@ch-avignon.fr

  • CHU JEAN MINJOZ - Service Hématologie

    Besançon, 25030

    Dr. Adrien CHAUCHET, +33 (0)3 81 66 82 32, achauchet@chu-besancon.fr

  • CHU ESTAING - Service Thérapie Cellulaire et Hématologie Clinique

    Clermont-Ferrand, 63003

    Dr. Sébastien BAILLY, +33 (0)4 73 75 00 65, s-bailly@chu-clermontferrand.fr

  • HOPITAL HENRI MONDOR - Unité Hémopathies Lymphoïdes

    Créteil, 94010

    Dr. François LEMONNIER, +33 (0)1 49 81 20 51, francois.lemonnier@aphp.fr

  • CHU DIJON BOURGOGNE - Service Hématologie Clinique

    Dijon, 21000

    Pr. Cédric ROSSI, +33 (0)6 80 29 50 41, cedric.rossi@chu-dijon.fr

  • CHD DE VENDEE - Service Hématologie

    La Roche-sur-Yon, 85925

    Dr. Antoine LEVEQUE, +33 (0)2 51 44 61 73, antoine.leveque@ght85.fr

  • CHU DE GRENOBLE - Service Hématologie

    La Tronche, 38700

    Dr. Sylvain CARRAS, +33 (0)4 76 76 57 55, scarras@chu-grenoble.fr

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

    Le Chesnay, 78157

    Dr. Aurélie CABANNES-HAMY, +33 (0)1 39 63 90 33, acabannes@ght78sud.fr

  • HOPITAL SAINT VINCENT-DE-PAUL - Service Hématologie Clinique

    Lille, 59020

    Dr. Sandy AMORIM, +33 03 20 87 45 32, amorim.sandy@ghicl.net

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

    Lille, 59037

    Pr. Franck MORSCHHAUSER, +33 (0)3 20 44 57 13, franck.morschhauser@chu-lille.fr

  • CENTRE LEON BERARD - Service Hématologie

    Lyon, 69373

    Dr. Sylvain LAMURE, +33 (0)4 69 85 61 93, sylvain.lamure@lyon.unicancer.fr

  • CHU DE MONTPELLIER - Département d'Hématologie Clinique

    Montpellier, 34295

    Dr. Charles HERBAUX, +33 (0)4 67 33 83 64, c-herbaux@chu-montpellier.fr

  • CHU DE NANTES - Service Hématologie

    Nantes, 44093

    Dr. Benoit TESSOULIN, +33 (0)2 40 08 32 71, benoit.tessoulin@chu-nantes.fr

  • CHU ORLEANS - Service Oncologie Médicale

    Orléans, 45067

    Dr. Marlène OCHMANN, +33 (0)2 38 57 52 54, marlene.ochmann@chu-orleans.fr

  • HOPITAL COCHIN - Hématologie clinique

    Paris, 75014

    Dr. Loïc RENAUD, +33 (0)1 42 11 45 07, loic.renaud@aphp.fr

  • HOPITAL SAINT-LOUIS - Service Hématologie Adolescents et Jeunes Adultes

    Paris, 75475

    Dr. Florian CHEVILLON, + 33 01 42 38 51 27, florian.chevillon@aphp.fr

  • HOPITAL DE LA PITIE SALPETRIERE - Service Hématologie Clinique

    Paris, 75651

    Dr. Daphné KRZISCH, +33 (0)1 84 82 84 94, daphne.krzisch@aphp.fr

  • HOPITAL NECKER - Service Hématologie Adultes

    Paris, 75743

    Dr. Morgane CHEMINANT, +33 (0)1 44 49 52 83, morgane.cheminant@aphp.fr

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

    Pessac, 33604

    Dr. François-Xavier GROS, +33 (0)5 57 65 65 11, francois-xavier.gros@chu-bordeaux.fr

  • CHU LYON-SUD - Hématologie Clinique

    Pierre-Bénite, 69495

    Dr. Pierre SESQUES, +33 (0)4 78 86 43 46, pierre.sesques@chu-lyon.fr

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

    Poitiers, 86021

    Dr. Stéphanie GUIDEZ, fr +33 (0)5 49 44 43 07, stephanie.guidez@chu-poitiers.fr

  • CHU DE REIMS - HOPITAL ROBERT DEBRE - Service Hématologie

    Reims, 51092

    Dr. Eric DUROT, +33 (0)6 64 77 25 61, edurot@chu-reims.fr

  • CHU PONTCHAILLOU - Hématologie Clinique

    Rennes, 35033

    Pr. Roch HOUOT, +33 (0)2 99 28 98 73, roch.houot@chu-rennes.fr

  • CENTRE HENRI BECQUEREL - Service Hématologie

    Rouen, 76038

    Dr. Vincent CAMUS, +33 (0)2 32 08 29 47, vincent.camus@chb.unicancer.fr

  • INSTITUT CURIE - SITE SAINT-CLOUD - Service Hématologie

    Saint-Cloud, 92210

    Dr. Adrien GILBERT, +33 (0)1 47 11 15 15, adrien.gilbert@curie.fr

  • IUCT ONCOPOLE - Service Hématologie

    Toulouse, 31059

    Dr. Lucie OBERIC, +33 (0)5 61 77 20 78, oberic.lucie@iuct-oncopole.fr

  • CHRU NANCY - HÔPITAL BRABOIS - Service Hématologie

    Vandœuvre-lès-Nancy, 54511

    Pr. Pierre FEUGIER, +33 (0)3 83 15 32 57, p.feugier@chru-nancy.fr

  • GUSTAVE ROUSSY CANCER CAMPUS GRAND PARIS - Département Médecine Oncologique

    Villejuif, 94085

    Dr. Vincent RIBRAG, +33 (0)1 42 11 45 07, vincent.ribrag@gustaveroussy.fr

Other trials in France

About this study

Official title: 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.

Read the 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.

Being tested
blood test
Keywords
Circulating Tumor DNA, Measurable Residual Disease, Large B-Cell Lymphoma, PhasED-Seq, PET-Scan in Lymphoma
Medical subject headings
Neoplasm, Residual

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • blood testOther

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

Study groups in NCT07514715
Study groupRoleWhat they receive
All participants will receive standard of care treatment only, according to local practice.Not described
Receives: Other: blood test

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (13)

  1. Survival

    Event Free Survival (EFS) by histology subtype

    Measured: at 1 year

  2. Progression/relapse

    Duration of response (DoR) as defined by Lugano 2014 criteria

    Measured: at 1 year

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

    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).

    Measured: at 1 year

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

    Number of participants with delayed results, and reasons associated.

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

  5. Survival

    Progression-free survival (PFS) by histology subtype

    Measured: 1year

  6. Survival

    Overall Survival (OS) by histology subtype

    Measured: 1year

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

    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).

    Measured: at 1 year

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

    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).

    Measured: at 1 year

  9. 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).

    Concordance rate between metabolic PET response and ctDNA result

    Measured: Each timepoint (pre-treatment, interim timepoint, end of treatment)

  10. To document and classify the reasons for unsuccessful ctDNA sampling, processing or result reporting.

    Number of participants with delayed results, and reasons associated.

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

  11. To assess the proportion of informative cfDNA samples for phased variant monitoring

    Proportion of samples with at least twenty phased variants detectable at baseline

    Measured: Baseline

  12. Describe the timelines for the delivery of the results of the centralized PET review.

    Proportions of participants for whom results are delivered within the predefined time frame in the protocol (time between the date of image acquisition or collection and the date of transmission to the investigator ≤ target time), at baseline (before interim evaluation) and at the end of treatment (≤ 5 weeks) with a 95% confidence interval.

    The observed delays (in calendar days) will also be described by their distribution (median, interquartile range, minimum-maximum)

    Measured: Two timepoints (Baseline, end of treatment)

  13. Describe the timelines for the delivery of the results of ctDNA results.

    Proportions of participants for whom results are delivered within the predefined time frame in the protocol (time between the date of blood collection and the date of transmission to the investigator ≤ target time), at baseline (before interim evaluation) and at the end of treatment (≤ 5 weeks), estimated globally and by RT4 platform with a 95% confidence interval.

    The observed delays (in calendar days) will also be described by their distribution (median, interquartile range, minimum-maximum), overall and by platform

    Measured: Two timepoints (Baseline, end of treatment)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Apr 2026
  2. Study start30 Jun 2026 (estimated)
  3. Primary completion1 Oct 2028 (estimated)
  4. Study completion1 Oct 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Other
Time perspective
Prospective
Enrolment
129 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07514715
Sponsor's protocol ID
RT4
Acronym
RT4
Status last verified
Jun 2026
First submitted
13 Mar 2026
Last updated
11 Jun 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 19544140

  • 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.

    PubMed 25113753

  • 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.

    PubMed 41385760

  • 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.

    PubMed 41428995

  • 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.

    PubMed 34294911

  • 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.

    PubMed 30125215

Questions about this trial

What is this clinical trial studying?

An observational study of Aggressive B-cell Lymphomas, run by The Lymphoma Academic Research Organisation at 30 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 29 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 11 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 30 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Project Management Project Management (+33 (0) 4 27 01 27 22, RT4@lysarc.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07514715, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2026.

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