Clinical trial NCT01599559: 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
Official title: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Primary Mediastinal B-cell Lymphoma
Keywords: previously
untreated
Lead sponsor: International Extranodal Lymphoma Study Group (IELSG)
Sponsor class: OTHER
First posted: 2012-05-16
Enrollment: 540
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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trial is to test whether radiation therapy is really necessary in patients where PET/CT has shown that the tumor is no longer active.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


Eligibility criteria: 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.

Primary outcomes:
measure: Progression free survival (PFS)
timeFrame: 30 months from the randomization
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: 5 years from registration
measure: Long term toxicity
timeFrame: 10 years from registration
Other outcomes:
Locations:
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Rochester
country: United States
facility: Mayo Clinil Rocheser
state: Minnesota
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Buenos Aires
country: Argentina
facility: Centro de Hematologia y Oncologia Pavlovsky
city: Toronto
country: Canada
facility: Princess Margaret Hospital
city: Shanghai
country: China
facility: Ruijin Hospital
city: Brno
country: Czechia
facility: Faculty Hospital Brno
city: Hradec Kralove
country: Czechia
facility: University Hospital
city: Prague
country: Czechia
facility: Faculty Hospital Kralovske Vinohrady
city: Prague
country: Czechia
facility: General University Hospital
city: Essen
country: Germany
facility: University of Duisburg-Essen, Campus Essen
city: Alessandria
country: Italy
facility: A.O. SS. Antonio e Biagio e Cesare Arrigo
city: Ancona
country: Italy
facility: Clinica di Ematologia Ospedali Riuniti "Umberto I"
city: Aviano
country: Italy
facility: Centro di Riferimento Oncologico - Aviano
city: Bari
country: Italy
facility: A.O.U Policlinico Consorziale di Bari
city: Bari
country: Italy
facility: Bari IRCCS Istituto Tumori
city: Barletta
country: Italy
facility: Ospedale Mons. Dimiccoli
city: Bergamo
country: Italy
facility: Ospedale Papa Giovanni Xxiii
city: Bologna
country: Italy
facility: Sant'Orsola Malpighi
city: Bolzano
country: Italy
facility: Comprensorio Sanitario di Bolzano
city: Brescia
country: Italy
facility: Spedali Civili
city: Brindisi
country: Italy
facility: Asl Uoc Ematologia A Perrino
city: Cagliari
country: Italy
facility: Ospedale Businco
city: Catania
country: Italy
facility: AO Garibaldi Nesima Catalia
city: Cuneo
country: Italy
facility: Ospedale S. Croce e Carle
city: Firenze
country: Italy
facility: Unità Funzionale di Ematologia AOU Careggi
city: Lecce
country: Italy
facility: U.O. Ematologia Vito Fazzi
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
city: Messina
country: Italy
facility: SC Ematologia Azienda Ospedali Riuniti Papardo Piemonte
city: Milano
country: Italy
facility: Istituto Scientifico San Raffaele
city: Milano
country: Italy
facility: Milano Ieo
city: Milano
country: Italy
facility: SC Ematologia AO Niguarda
city: Modena
country: Italy
facility: AOU Policlinico di Modena
city: Napoli
country: Italy
facility: Ematologia Università degli Studi di Federico II
city: Nocera
country: Italy
facility: Ospedale Umberto I
city: Padova
country: Italy
facility: Azienda Ospedaliera Universitaria
city: Palermo
country: Italy
facility: Ospedali Riuniti Villa Sofia
city: Parma
country: Italy
facility: AOU di Parma
city: Pavia
country: Italy
facility: Fondazione IRCCS S. Matteo
city: Perugia
country: Italy
facility: S.C. Ematologia Ospedale S. Marid Della Misericordia
city: Pescara
country: Italy
facility: Ospedale Civile di Pescara
city: Piacenza
country: Italy
facility: Ospedale Civico Guglielmo di Saliceto
city: Potenza
country: Italy
facility: Ospedale San Carlo di Potenza
city: Ravenna
country: Italy
facility: U.O. Oncologia Ematologia Ospedale S. Maria Delle Croci
city: Reggio Calabria
country: Italy
facility: A.O. Bianchi-Melacrino-Morelli, Divisione di Ematologia
city: Reggio Emilia
country: Italy
facility: ICCRS Azienda Ospedaliera Arcipedale "Santa Maria Nuova"
city: Rimini
country: Italy
facility: Ospedale Degli Infermi
city: Roma
country: Italy
facility: Fondazione PTV Policlinico Tor Vergata
city: Roma
country: Italy
facility: AO San Camillo Forlanini
city: Roma
country: Italy
facility: AOU S. Andrea Roma
city: Roma
country: Italy
facility: Ospedale S. Eugenio
city: Roma
country: Italy
facility: Policlinico Universitario Campus Bio-Medico
city: Roma
country: Italy
facility: Roma Regina Elena IFO
city: Roma
country: Italy
facility: Roma San Giovanni
city: Roma
country: Italy
facility: Università degli Studi La Sapienza
city: Rozzano
country: Italy
facility: Rozzano Humanitas
city: Siena
country: Italy
facility: Siena
city: Terni
country: Italy
facility: AOS Maria di Terni
city: Torino
country: Italy
facility: AOS S. Giovanni Battista "Molinette"
city: Torino
country: Italy
facility: Azienda Ospedaliera Citta Della Salute E Della Scienza Di Torino
city: Tricase
country: Italy
facility: Ospedale Cardinale Panico
city: Udine
country: Italy
facility: Azienda Ospedaliera Univesritaria
city: Varese
country: Italy
facility: Asst Settelaghi Ospedale Macchi
city: Oslo
country: Norway
facility: Oslo University Hospital
city: Trondheim
country: Norway
facility: St Olavs Hospital
city: Warsaw
country: Poland
facility: Warsaw Centrum Onkologi Instytucie
city: Lisboa
country: Portugal
facility: Istituto Portugues de Oncologia de Lisboa
city: Lund
country: Sweden
facility: Lund Universitet
city: Bellinzona
country: Switzerland
facility: IOSI
city: Bern
country: Switzerland
facility: Inselspital Bern
city: Olten
country: Switzerland
facility: Kantonsspital Olten
city: St Gallen
country: Switzerland
facility: Kantonsspital
city: Kiev
country: Ukraine
facility: Kyiv National Cancer Institute
city: Basingstoke
country: United Kingdom
facility: Basingstoke & North Hamptshire Hospital
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
city: Glasgow
country: United Kingdom
facility: Glasgow Beatson Cancer Center
city: Leeds
country: United Kingdom
facility: Leeds St. James's Hospital
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital
city: London
country: United Kingdom
facility: Guy's & St. Thomas London
city: London
country: United Kingdom
facility: UCLH St. Thomas
city: Manchester
country: United Kingdom
facility: Manchester The Christie NHS Foundation Trust
city: Newcastle
country: United Kingdom
facility: Newcastle Freeman Hospital
city: Norfolk
country: United Kingdom
facility: Norfolk & Norwich University Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospital
city: Southampton
country: United Kingdom
facility: General Hospital
Study officials:
affiliation: Università La Sapienza (Rome - Italy)
name: Maurizio Martelli, MD
role: STUDY_CHAIR
affiliation: University of Southampton (UK)
name: Andrew J Davies, MD
role: STUDY_CHAIR
affiliation: Princess Margaret Hospital Toronto (Canada)
name: Mary Gospodarowicz, MD
role: STUDY_CHAIR
affiliation: St. Thomas' - London (UK)
name: Sally F Barrington, MD
role: STUDY_CHAIR
affiliation: AO S. Croce e Carle, Cuneo (Italia)
name: Alberto Biggi, MD
role: STUDY_CHAIR
affiliation: S.Maria Nuova Hospital, Reggio Emilia (Italia)
name: Annibale Versari, MD
role: STUDY_CHAIR
affiliation: CPO Torino (Italy)
name: Gianni Ciccone, MD
role: STUDY_CHAIR
affiliation: AO S. Crtoce e Carle - Cuneo (Italy)
name: Stèphane Chauvie, MD
role: STUDY_CHAIR
affiliation: IOSI - Bellinzona (Switzerland)
name: Luca Ceriani, MD
role: STUDY_CHAIR
References: