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

NCT01599559 | Active Not Recruiting DMC

• 1 other identifier: IELSG37
• Study Type: interventional
• Target: 540
• Locations: 14 countries
• Sites: 85

Brief Summary

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trial is to test whether radiation therapy is really necessary in patients where PET/CT has shown that the tumor is no longer active.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.

Conditions

Primary Mediastinal B-cell Lymphoma

Keywords

previously; untreated

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS)

  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 Outcomes (2)

• Overall survival (OS)

  5 years from registration

• Long term toxicity

  10 years from registration

Study Arms (2)

observation

EXPERIMENTAL

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

mediastinal irradiation

ACTIVE COMPARATOR

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)

Interventions

observation OTHER

observation

observation

3D-Conformal Radiotherapy (3D-CRT) RADIATION

Radiation treatment should start within 6-8 weeks after the end of chemotherapy.

mediastinal irradiation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• International Extranodal Lymphoma Study Group (IELSG): lead

Study Sites (85)

Norton Cancer Institute

Louisville, Kentucky, United States

Location

Mayo Clinil Rocheser

Rochester, Minnesota, 55905, United States

Location

MD Anderson Cancer Center

Houston, Texas, United States

Location

Centro de Hematologia y Oncologia Pavlovsky

Buenos Aires, Argentina

Location

Princess Margaret Hospital

Toronto, Canada

Location

Ruijin Hospital

Shanghai, China

Location

Faculty Hospital Brno

Brno, Czechia

Location

University Hospital

Hradec Králové, Czechia

Location

Faculty Hospital Kralovske Vinohrady

Prague, Czechia

Location

General University Hospital

Prague, Czechia

Location

University of Duisburg-Essen, Campus Essen

Essen, Germany

Location

A.O. SS. Antonio e Biagio e Cesare Arrigo

Alessandria, Italy

Location

Clinica di Ematologia Ospedali Riuniti "Umberto I"

Ancona, Italy

Location

Centro di Riferimento Oncologico - Aviano

Aviano, Italy

Location

A.O.U Policlinico Consorziale di Bari

Bari, Italy

Location

Bari IRCCS Istituto Tumori

Bari, Italy

Location

Ospedale Mons. Dimiccoli

Barletta, Italy

Location

Ospedale Papa Giovanni Xxiii

Bergamo, Italy

Location

Sant'Orsola Malpighi

Bologna, Italy

Location

Comprensorio Sanitario di Bolzano

Bolzano, Italy

Location

Spedali Civili

Brescia, Italy

Location

Asl Uoc Ematologia A Perrino

Brindisi, Italy

Location

Ospedale Businco

Cagliari, Italy

Location

AO Garibaldi Nesima Catalia

Catania, Italy

Location

Ospedale S. Croce e Carle

Cuneo, Italy

Location

Unità Funzionale di Ematologia AOU Careggi

Florence, Italy

Location

U.O. Ematologia Vito Fazzi

Lecce, Italy

Location

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, Italy

Location

SC Ematologia Azienda Ospedali Riuniti Papardo Piemonte

Messina, Italy

Location

Istituto Scientifico San Raffaele

Milan, Italy

Location

Milano Ieo

Milan, Italy

Location

SC Ematologia AO Niguarda

Milan, Italy

Location

AOU Policlinico di Modena

Modena, Italy

Location

Ematologia Università degli Studi di Federico II

Naples, Italy

Location

Ospedale Umberto I

Nocera Inferiore, Italy

Location

Azienda Ospedaliera Universitaria

Padua, Italy

Location

Ospedali Riuniti Villa Sofia

Palermo, Italy

Location

AOU di Parma

Parma, Italy

Location

Fondazione IRCCS S. Matteo

Pavia, Italy

Location

S.C. Ematologia Ospedale S. Marid Della Misericordia

Perugia, Italy

Location

Ospedale Civile di Pescara

Pescara, Italy

Location

Ospedale Civico Guglielmo di Saliceto

Piacenza, Italy

Location

Ospedale San Carlo di Potenza

Potenza, Italy

Location

U.O. Oncologia Ematologia Ospedale S. Maria Delle Croci

Ravenna, Italy

Location

A.O. Bianchi-Melacrino-Morelli, Divisione di Ematologia

Reggio Calabria, Italy

Location

ICCRS Azienda Ospedaliera Arcipedale "Santa Maria Nuova"

Reggio Emilia, Italy

Location

Ospedale Degli Infermi

Rimini, Italy

Location

Fondazione PTV Policlinico Tor Vergata

Roma, 00133, Italy

Location

AO San Camillo Forlanini

Roma, Italy

Location

AOU S. Andrea Roma

Roma, Italy

Location

Ospedale S. Eugenio

Roma, Italy

Location

Policlinico Universitario Campus Bio-Medico

Roma, Italy

Location

Roma Regina Elena IFO

Roma, Italy

Location

Roma San Giovanni

Roma, Italy

Location

Università degli Studi La Sapienza

Roma, Italy

Location

Rozzano Humanitas

Rozzano, Italy

Location

Siena

Siena, Italy

Location

AOS Maria di Terni

Terni, Italy

Location

AOS S. Giovanni Battista "Molinette"

Torino, Italy

Location

Azienda Ospedaliera Citta Della Salute E Della Scienza Di Torino

Torino, Italy

Location

Ospedale Cardinale Panico

Tricase, Italy

Location

Azienda Ospedaliera Univesritaria

Udine, Italy

Location

Asst Settelaghi Ospedale Macchi

Varese, Italy

Location

Oslo University Hospital

Oslo, Norway

Location

St Olavs Hospital

Trondheim, Norway

Location

Warsaw Centrum Onkologi Instytucie

Warsaw, Poland

Location

Istituto Portugues de Oncologia de Lisboa

Lisbon, Portugal

Location

Lund Universitet

Lund, Sweden

Location

IOSI

Bellinzona, 6500, Switzerland

Location

Inselspital Bern

Bern, Switzerland

Location

Kantonsspital Olten

Olten, Switzerland

Location

Kantonsspital

Sankt Gallen, Switzerland

Location

Kyiv National Cancer Institute

Kiev, Ukraine

Location

Basingstoke & North Hamptshire Hospital

Basingstoke, United Kingdom

Location

Birmingham Heartlands Hospital

Birmingham, United Kingdom

Location

Glasgow Beatson Cancer Center

Glasgow, United Kingdom

Location

Leeds St. James's Hospital

Leeds, United Kingdom

Location

Royal Liverpool University Hospital

Liverpool, United Kingdom

Location

Guy's & St. Thomas London

London, United Kingdom

Location

UCLH St. Thomas

London, United Kingdom

Location

Manchester The Christie NHS Foundation Trust

Manchester, United Kingdom

Location

Newcastle Freeman Hospital

Newcastle, United Kingdom

Location

Norfolk & Norwich University Hospital

Norfolk, United Kingdom

Location

Nottingham University Hospital

Nottingham, United Kingdom

Location

General Hospital

Southampton, United Kingdom

Location

Related Publications (2)

• Zucca E, Ceriani L, Ciccone G, Di Rocco A, Pirosa MC, Kriachok I, Botto B, Balzarotti M, Tucci A, Usai SV, Zilioli VR, Pennese E, Arcaini L, Dabrowska-Iwanicka A, Ferreri AJM, Merli F, Zhao W, Rigacci L, Cellini C, Hodgson D, Ionescu C, Minoia C, Lucchini E, Spina M, Fossa A, Janikova A, Cwynarski K, Mikhaeel NG, Jerkeman M, Stathis A, Cozens K, Ielmini N, De Martino I, Walewski J, Trneny M, Cavalli F, Ricardi U, Johnson PWM, Davies A, Martelli M. Impact of immunochemotherapy regimens on outcomes of patients with primary mediastinal B-cell lymphoma in the IELSG37 trial. Blood. 2025 Dec 4;146(23):2758-2764. doi: 10.1182/blood.2025028823.

  PMID: 40939190 DERIVED

• Martelli M, Ceriani L, Ciccone G, Ricardi U, Kriachok I, Botto B, Balzarotti M, Tucci A, Usai SV, Zilioli VR, Pennese E, Arcaini L, Dabrowska-Iwanicka A, Ferreri AJM, Merli F, Zhao W, Rigacci L, Cellini C, Hodgson D, Ionescu C, Minoia C, Lucchini E, Spina M, Fossa A, Janikova A, Cwynarski K, Mikhaeel G, Jerkeman M, Di Rocco A, Stepanishyna Y, Vitolo U, Santoro A, Re A, Puccini B, Olivieri J, Petrucci L, Barrington SF, Malkowski B, Metser U, Versari A, Chauvie S, Walewski J, Trneny M, Cavalli F, Gospodarowicz M, Johnson PWM, Davies A, Zucca E; International Extranodal Lymphoma Study Group (IELSG). Omission of Radiotherapy in Primary Mediastinal B-Cell Lymphoma: IELSG37 Trial Results. J Clin Oncol. 2024 Dec;42(34):4071-4083. doi: 10.1200/JCO-24-01373. Epub 2024 Aug 19.

  PMID: 39159403 DERIVED

MeSH Terms

Interventions

Observation; Radiotherapy, Conformal

Intervention Hierarchy (Ancestors)

Methods; Investigative Techniques; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Study Officials

• 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)

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2012
• First Posted: May 16, 2012
• Study Start: October 1, 2012
• Primary Completion: June 17, 2022
• Study Completion (Estimated): December 17, 2029
• Last Updated: January 15, 2026

Record last verified: 2026-01

Locations

CH (4); IT (52); AR (1); DE (1); GB (12); CN (1); CZ (4); NO (2); PL (1); UA (1); US (3); CA (1); PT (1); SE (1)