Randomized, Open-label, Two-arms, Phase III Comparative Study Assessing the Role of Involved Mediastinal Radiotherapy After Rituximab Containing Chemotherapy Regimens to Patients With Newly Diagnosed Primary Mediastinal Large B-Cell Lymphoma

January 14, 2026 updated by: International Extranodal Lymphoma Study Group (IELSG)

IELSG37: A Randomized, Open-label, Multicentre, Two-arm Phase III Comparative Study Assessing the Role of Involved Mediastinal Radiotherapy After Rituximab Containing Chemotherapy Regimens to Patients With Newly Diagnosed Primary Mediastinal Large B-Cell Lymphoma (PMLBCL)

Primary mediastinal large B cell lymphoma is treated with a combination of chemotherapy and the monoclonal antibody rituximab (chemoimmunotherapy).

Following chemoimmunotherapy patients receive radiation therapy if they have residues which may be active tumour. However at the end of chemoimmunotherapy the majority of patients show tissue scarring that is not necessarily active tumor. In recent years, PET/CT has proved to be a good tool to accurately identify active tumor from scar tissue in patients treated for mediastinal lymphoma.The purpose of this trial is to test whether radiation therapy is really necessary in patients where PET/CT has shown that the tumor is no longer active. Therefore we will compare radiation treatment with careful observation.

Patients that at the end of conventional treatment of chemoimmunotherapy have a negative PET/CT (i.e., without residues suspected to contain active tumor), will randomly assigned to two different treatment groups: one treatment group will receive the radiation treatment, and the other treatment group will receive careful observation.

The trial is planned according to a non-inferiority design aimed at demonstrating that progression free survival after the experimental treatment (observation) is not worse than after the standard comparator (mediastinal irradiation.Participation in this study could spare patients with complete remission at the end of chemo immunotherapy (PET/CT negative) radiation therapy that may be unnecessary.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

540

Phase

  • Not Applicable

Contacts and Locations

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

Study Locations

  • Argentina
      • Buenos Aires, Argentina
        • Centro de Hematologia y Oncologia Pavlovsky
  • Canada
      • Toronto, Canada
        • Princess Margaret Hospital
  • China
      • Shanghai, China
        • Ruijin Hospital
  • Czechia
      • Brno, Czechia
        • Faculty Hospital Brno
      • Hradec Králové, Czechia
        • University Hospital
      • Prague, Czechia
        • General University Hospital
      • Prague, Czechia
        • Faculty Hospital Královské Vinohrady
  • Germany
      • Essen, Germany
        • University of Duisburg-Essen, Campus Essen
  • Italy
      • Alessandria, Italy
        • A.O. SS. Antonio e Biagio e Cesare Arrigo
      • Ancona, Italy
        • Clinica di Ematologia Ospedali Riuniti "Umberto I"
      • Aviano, Italy
        • Centro di Riferimento Oncologico - Aviano
      • Bari, Italy
        • A.O.U Policlinico Consorziale di Bari
      • Bari, Italy
        • Bari IRCCS Istituto Tumori
      • Barletta, Italy
        • Ospedale Mons. Dimiccoli
      • Bergamo, Italy
        • Ospedale Papa Giovanni XXIII
      • Bologna, Italy
        • Sant'Orsola Malpighi
      • Bolzano, Italy
        • Comprensorio Sanitario di Bolzano
      • Brescia, Italy
        • Spedali Civili
      • Brindisi, Italy
        • Asl Uoc Ematologia A Perrino
      • Cagliari, Italy
        • Ospedale Businco
      • Catania, Italy
        • AO Garibaldi Nesima Catalia
      • Cuneo, Italy
        • Ospedale S. Croce e Carle
      • Florence, Italy
        • Unità Funzionale di Ematologia AOU Careggi
      • Lecce, Italy
        • U.O. Ematologia Vito Fazzi
      • Meldola, Italy
        • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
      • Messina, Italy
        • SC Ematologia Azienda Ospedali Riuniti Papardo Piemonte
      • Milan, Italy
        • Istituto Scientifico San Raffaele
      • Milan, Italy
        • Milano Ieo
      • Milan, Italy
        • SC Ematologia AO Niguarda
      • Modena, Italy
        • AOU Policlinico di Modena
      • Napoli, Italy
        • Ematologia Università degli Studi di Federico II
      • Nocera Inferiore, Italy
        • Ospedale Umberto I
      • Padua, Italy
        • Azienda Ospedaliera Universitaria
      • Palermo, Italy
        • Ospedali Riuniti Villa Sofia
      • Parma, Italy
        • AOU di Parma
      • Pavia, Italy
        • Fondazione IRCCS S. Matteo
      • Perugia, Italy
        • S.C. Ematologia Ospedale S. Marid Della Misericordia
      • Pescara, Italy
        • Ospedale Civile di Pescara
      • Piacenza, Italy
        • Ospedale Civico Guglielmo di Saliceto
      • Potenza, Italy
        • Ospedale San Carlo di Potenza
      • Ravenna, Italy
        • U.O. Oncologia Ematologia Ospedale S. Maria Delle Croci
      • Reggio Calabria, Italy
        • A.O. Bianchi-Melacrino-Morelli, Divisione di Ematologia
      • Reggio Emilia, Italy
        • ICCRS Azienda Ospedaliera Arcipedale "Santa Maria Nuova"
      • Rimini, Italy
        • Ospedale degli Infermi
      • Roma, Italy
        • AO San Camillo Forlanini
      • Roma, Italy
        • Ospedale S. Eugenio
      • Roma, Italy, 00133
        • Fondazione PTV Policlinico Tor Vergata
      • Roma, Italy
        • Policlinico Universitario Campus Bio-Medico
      • Roma, Italy
        • Universita Degli Studi La Sapienza
      • Roma, Italy
        • AOU S. Andrea Roma
      • Roma, Italy
        • Roma Regina Elena IFO
      • Roma, Italy
        • Roma San Giovanni
      • Rozzano, Italy
        • Rozzano Humanitas
      • Siena, Italy
        • Siena
      • Terni, Italy
        • AOS Maria di Terni
      • Torino, Italy
        • Azienda Ospedaliera Città della Salute e della Scienza di Torino
      • Torino, Italy
        • AOS S. Giovanni Battista "Molinette"
      • Tricase, Italy
        • Ospedale Cardinale Panico
      • Udine, Italy
        • Azienda Ospedaliera Univesritaria
      • Varese, Italy
        • Asst Settelaghi Ospedale Macchi
  • Norway
      • Oslo, Norway
        • Oslo University Hospital
      • Trondheim, Norway
        • St Olavs hospital
  • Poland
      • Warsaw, Poland
        • Warsaw Centrum Onkologi Instytucie
  • Portugal
      • Lisbon, Portugal
        • Istituto Portugues de Oncologia de Lisboa
  • Sweden
      • Lund, Sweden
        • Lund Universitet
  • Switzerland
      • Bellinzona, Switzerland, 6500
        • IOSI
      • Bern, Switzerland
        • Inselspital Bern
      • Olten, Switzerland
        • Kantonsspital Olten
      • Sankt Gallen, Switzerland
        • Kantonsspital
  • Ukraine
      • Kiev, Ukraine
        • Kyiv National Cancer Institute
  • United Kingdom
      • Basingstoke, United Kingdom
        • Basingstoke & North Hamptshire Hospital
      • Birmingham, United Kingdom
        • Birmingham Heartlands Hospital
      • Glasgow, United Kingdom
        • Glasgow Beatson Cancer Center
      • Leeds, United Kingdom
        • Leeds St. James's Hospital
      • Liverpool, United Kingdom
        • Royal Liverpool University Hospital
      • London, United Kingdom
        • Guy's & St. Thomas London
      • London, United Kingdom
        • UCLH St. Thomas
      • Manchester, United Kingdom
        • Manchester The Christie NHS Foundation Trust
      • Newcastle, United Kingdom
        • Newcastle Freeman Hospital
      • Norfolk, United Kingdom
        • Norfolk & Norwich University Hospital
      • Nottingham, United Kingdom
        • Nottingham University Hospital
      • Southampton, United Kingdom
        • General Hospital
  • United States
    • Kentucky
      • Louisville, Kentucky, United States
        • Norton Cancer Institute
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinil Rocheser
    • Texas
      • Houston, Texas, United States
        • MD Anderson Cancer Center

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Previously untreated primary mediastinal diffuse large B-cell lymphoma, CD20 positive.
  • Patients must have histological confirmation of the diagnosis (it is recommended that the immunohistochemical panel includes: CD45, CD20, CD30, CD15, CD10, BCL6, BCL2, MUM-1), and in addition have a dominant mass within the anterior mediastinum.
  • No evidence of extranodal disease outside the chest including spleen and bone marrow.
  • Age at least 18 years.
  • Fit to receive chemotherapy and radiotherapy with curative intent.
  • Patients will be eligible if the treatment phase consisting in a Rituximab combined with any anthracycline-containing chemotherapy regimen without consolidation with autologous stem cell support (e.g., 6 cycles of CHOP14-21, DA-EPOCH, Mega-CHOP or 12 weeks of VACOP-B or MACOP-B).
  • At least 6 courses of Rituximab should be administered
  • Able and willing to give informed consent, and to undergo staging including PET scanning
  • Willingness to comply with an appropriate contraceptive method in women of childbearing potential or men.
  • Histological diagnostic material available for review.

Exclusion Criteria:

  • History of malignancy other than squamous cell carcinoma, basal cell carcinoma of the skin or carcinoma in situ of the cervix within the last 5 years.
  • Evidence of clinically significant cardiac disease at diagnosis, as defined by history of symptomatic ventricular arrhythmias, congestive heart failure or myocardial infarction within 12 months before study entry. Cardiac impairment due to local extension of lymphoma will not be an exclusion criterion in the absence of other cardiac disease.
  • Known HIV-positive serology.
  • Pregnant or lactating women.
  • Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.

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

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: observation
Follow up visits are scheduled from randomization. Patients will be seen at 3-months intervals for 24 months, then every 6 months until 5 years from randomization.
Other: observation
observation
Active Comparator: mediastinal irradiation
Radiotherapy will be delivered in this phase III protocol, as alternative to observation, as consolidation treatment in patients achieving a CR status (PET/CT scan negative) at the end of R-chemotherapy, with a total dose of 30 Gy.
Radiation: 3D-Conformal Radiotherapy (3D-CRT)
Radiation treatment should start within 6-8 weeks after the end of chemotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression free survival (PFS)
Time Frame: 30 months from the randomization

The primary outcome endpoint will be Progression Free Survival (PFS) in patients PET-negative after R-chemotherapy.

Failure events for PFS are progression (defined as an increase in size of existing masses or the development of new sites of disease using the same radiological investigations CT or PET/CT and/or MRI - as for the pre-chemotherapy assessment) or death from any cause.
30 months from the randomization

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival (OS)
Time Frame: 5 years from registration
OS is defined as the time from registration until death as a result of any cause until five years from registration
5 years from registration
Long term toxicity
Time Frame: 10 years from registration
Reporting of any adverse event which is judged in the opinion of investigator to be possibly treatment-related up to 10 years from randomization (including all cardiac and pulmonary events, relapses and second cancers and deaths)
10 years from registration

Collaborators and Investigators

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

Sponsor

International Extranodal Lymphoma Study Group (IELSG)

Investigators

  • Study Chair: Maurizio Martelli, MD, Università La Sapienza (Rome - Italy)
  • Study Chair: Andrew J Davies, MD, University of Southampton (UK)
  • Study Chair: Mary Gospodarowicz, MD, Princess Margaret Hospital Toronto (Canada)
  • Study Chair: Sally F Barrington, MD, St. Thomas' - London (UK)
  • Study Chair: Alberto Biggi, MD, AO S. Croce e Carle, Cuneo (Italia)
  • Study Chair: Annibale Versari, MD, S.Maria Nuova Hospital, Reggio Emilia (Italia)
  • Study Chair: Gianni Ciccone, MD, CPO Torino (Italy)
  • Study Chair: Stèphane Chauvie, MD, AO S. Crtoce e Carle - Cuneo (Italy)
  • Study Chair: Luca Ceriani, MD, IOSI - Bellinzona (Switzerland)

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 (Actual)

October 1, 2012

Primary Completion (Actual)

June 17, 2022

Study Completion (Estimated)

December 17, 2029

Study Registration Dates

First Submitted

May 10, 2012

First Submitted That Met QC Criteria

May 15, 2012

First Posted (Estimated)

May 16, 2012

Study Record Updates

Last Update Posted (Estimated)

January 15, 2026

Last Update Submitted That Met QC Criteria

January 14, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IELSG37

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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