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

NCT ID: NCT01599559

Last Updated: 2026-01-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

NA

Total Enrollment

540 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-10-31

Study Completion Date

2029-12-17

Brief Summary

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trial is to test whether radiation therapy is really necessary in patients where PET/CT has shown that the tumor is no longer active.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

Detailed Description

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Conditions

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Primary Mediastinal B-cell Lymphoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

observation

Intervention Type OTHER

observation

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.

Group Type ACTIVE_COMPARATOR

3D-Conformal Radiotherapy (3D-CRT)

Intervention Type RADIATION

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

Interventions

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observation

observation

Intervention Type OTHER

3D-Conformal Radiotherapy (3D-CRT)

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

Intervention Type RADIATION

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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International Extranodal Lymphoma Study Group (IELSG)

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Maurizio Martelli, MD

Role: STUDY_CHAIR

Università La Sapienza (Rome - Italy)

Andrew J Davies, MD

Role: STUDY_CHAIR

University of Southampton (UK)

Mary Gospodarowicz, MD

Role: STUDY_CHAIR

Princess Margaret Hospital Toronto (Canada)

Sally F Barrington, MD

Role: STUDY_CHAIR

St. Thomas' - London (UK)

Alberto Biggi, MD

Role: STUDY_CHAIR

AO S. Croce e Carle, Cuneo (Italia)

Annibale Versari, MD

Role: STUDY_CHAIR

S.Maria Nuova Hospital, Reggio Emilia (Italia)

Gianni Ciccone, MD

Role: STUDY_CHAIR

CPO Torino (Italy)

Stèphane Chauvie, MD

Role: STUDY_CHAIR

AO S. Crtoce e Carle - Cuneo (Italy)

Luca Ceriani, MD

Role: STUDY_CHAIR

IOSI - Bellinzona (Switzerland)

Locations

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Norton Cancer Institute

Louisville, Kentucky, United States

Site Status

Mayo Clinil Rocheser

Rochester, Minnesota, United States

Site Status

MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Centro de Hematologia y Oncologia Pavlovsky

Buenos Aires, , Argentina

Site Status

Princess Margaret Hospital

Toronto, , Canada

Site Status

Ruijin Hospital

Shanghai, , China

Site Status

Faculty Hospital Brno

Brno, , Czechia

Site Status

University Hospital

Hradec Králové, , Czechia

Site Status

Faculty Hospital Kralovske Vinohrady

Prague, , Czechia

Site Status

General University Hospital

Prague, , Czechia

Site Status

University of Duisburg-Essen, Campus Essen

Essen, , Germany

Site Status

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

Alessandria, , Italy

Site Status

Clinica di Ematologia Ospedali Riuniti "Umberto I"

Ancona, , Italy

Site Status

Centro di Riferimento Oncologico - Aviano

Aviano, , Italy

Site Status

A.O.U Policlinico Consorziale di Bari

Bari, , Italy

Site Status

Bari IRCCS Istituto Tumori

Bari, , Italy

Site Status

Ospedale Mons. Dimiccoli

Barletta, , Italy

Site Status

Ospedale Papa Giovanni Xxiii

Bergamo, , Italy

Site Status

Sant'Orsola Malpighi

Bologna, , Italy

Site Status

Comprensorio Sanitario di Bolzano

Bolzano, , Italy

Site Status

Spedali Civili

Brescia, , Italy

Site Status

Asl Uoc Ematologia A Perrino

Brindisi, , Italy

Site Status

Ospedale Businco

Cagliari, , Italy

Site Status

AO Garibaldi Nesima Catalia

Catania, , Italy

Site Status

Ospedale S. Croce e Carle

Cuneo, , Italy

Site Status

Unità Funzionale di Ematologia AOU Careggi

Florence, , Italy

Site Status

U.O. Ematologia Vito Fazzi

Lecce, , Italy

Site Status

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, , Italy

Site Status

SC Ematologia Azienda Ospedali Riuniti Papardo Piemonte

Messina, , Italy

Site Status

Istituto Scientifico San Raffaele

Milan, , Italy

Site Status

Milano Ieo

Milan, , Italy

Site Status

SC Ematologia AO Niguarda

Milan, , Italy

Site Status

AOU Policlinico di Modena

Modena, , Italy

Site Status

Ematologia Università degli Studi di Federico II

Napoli, , Italy

Site Status

Ospedale Umberto I

Nocera Inferiore, , Italy

Site Status

Azienda Ospedaliera Universitaria

Padua, , Italy

Site Status

Ospedali Riuniti Villa Sofia

Palermo, , Italy

Site Status

AOU di Parma

Parma, , Italy

Site Status

Fondazione IRCCS S. Matteo

Pavia, , Italy

Site Status

S.C. Ematologia Ospedale S. Marid Della Misericordia

Perugia, , Italy

Site Status

Ospedale Civile di Pescara

Pescara, , Italy

Site Status

Ospedale Civico Guglielmo di Saliceto

Piacenza, , Italy

Site Status

Ospedale San Carlo di Potenza

Potenza, , Italy

Site Status

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

Ravenna, , Italy

Site Status

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

Reggio Calabria, , Italy

Site Status

ICCRS Azienda Ospedaliera Arcipedale "Santa Maria Nuova"

Reggio Emilia, , Italy

Site Status

Ospedale Degli Infermi

Rimini, , Italy

Site Status

Fondazione PTV Policlinico Tor Vergata

Roma, , Italy

Site Status

AO San Camillo Forlanini

Roma, , Italy

Site Status

AOU S. Andrea Roma

Roma, , Italy

Site Status

Ospedale S. Eugenio

Roma, , Italy

Site Status

Policlinico Universitario Campus Bio-Medico

Roma, , Italy

Site Status

Roma Regina Elena IFO

Roma, , Italy

Site Status

Roma San Giovanni

Roma, , Italy

Site Status

Università degli Studi La Sapienza

Roma, , Italy

Site Status

Rozzano Humanitas

Rozzano, , Italy

Site Status

Siena

Siena, , Italy

Site Status

AOS Maria di Terni

Terni, , Italy

Site Status

AOS S. Giovanni Battista "Molinette"

Torino, , Italy

Site Status

Azienda Ospedaliera Citta Della Salute E Della Scienza Di Torino

Torino, , Italy

Site Status

Ospedale Cardinale Panico

Tricase, , Italy

Site Status

Azienda Ospedaliera Univesritaria

Udine, , Italy

Site Status

Asst Settelaghi Ospedale Macchi

Varese, , Italy

Site Status

Oslo University Hospital

Oslo, , Norway

Site Status

St Olavs Hospital

Trondheim, , Norway

Site Status

Warsaw Centrum Onkologi Instytucie

Warsaw, , Poland

Site Status

Istituto Portugues de Oncologia de Lisboa

Lisbon, , Portugal

Site Status

Lund Universitet

Lund, , Sweden

Site Status

IOSI

Bellinzona, , Switzerland

Site Status

Inselspital Bern

Bern, , Switzerland

Site Status

Kantonsspital Olten

Olten, , Switzerland

Site Status

Kantonsspital

Sankt Gallen, , Switzerland

Site Status

Kyiv National Cancer Institute

Kiev, , Ukraine

Site Status

Basingstoke & North Hamptshire Hospital

Basingstoke, , United Kingdom

Site Status

Birmingham Heartlands Hospital

Birmingham, , United Kingdom

Site Status

Glasgow Beatson Cancer Center

Glasgow, , United Kingdom

Site Status

Leeds St. James's Hospital

Leeds, , United Kingdom

Site Status

Royal Liverpool University Hospital

Liverpool, , United Kingdom

Site Status

Guy's & St. Thomas London

London, , United Kingdom

Site Status

UCLH St. Thomas

London, , United Kingdom

Site Status

Manchester The Christie NHS Foundation Trust

Manchester, , United Kingdom

Site Status

Newcastle Freeman Hospital

Newcastle, , United Kingdom

Site Status

Norfolk & Norwich University Hospital

Norfolk, , United Kingdom

Site Status

Nottingham University Hospital

Nottingham, , United Kingdom

Site Status

General Hospital

Southampton, , United Kingdom

Site Status

Countries

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United States Argentina Canada China Czechia Germany Italy Norway Poland Portugal Sweden Switzerland Ukraine United Kingdom

References

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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.

Reference Type DERIVED
PMID: 40939190 (View on PubMed)

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.

Reference Type DERIVED
PMID: 39159403 (View on PubMed)

Other Identifiers

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IELSG37

Identifier Type: -

Identifier Source: org_study_id

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