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

Primary Mediastinal B-cell Lymphoma Clinical Trial

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01599559
• Other study ID #: IELSG37
• Status: Active, not recruiting
• Phase: N/A
• Start date: October 2012
• Est. completion date: December 17, 2029

Study information

• Verified date: October 2023
• Source: International Extranodal Lymphoma Study Group (IELSG)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

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trial is to test whether radiation therapy is really necessary in patients where PET/CT has shown that the tumor is no longer active.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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 540
• Est. completion date: December 17, 2029
• Est. primary completion date: June 17, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell
• Primary Mediastinal B-cell Lymphoma

Intervention

Other:
• observation
observation

Radiation:
• 3D-Conformal Radiotherapy (3D-CRT)
Radiation treatment should start within 6-8 weeks after the end of chemotherapy.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
International Extranodal Lymphoma Study Group (IELSG)

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall survival (OS)	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
Secondary	Long term toxicity	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