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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 Purpose

Primary Mediastinal B-cell Lymphoma

Status

Active

Phase

Not Applicable

Locations

International

Study Type

Interventional

Intervention

observation

3D-Conformal Radiotherapy (3D-CRT)

About this trial

This is an interventional treatment trial for Primary Mediastinal B-cell Lymphoma focused on measuring previously, untreated

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Norton Cancer Institute
Mayo Clinil Rocheser
MD Anderson Cancer Center
Centro de Hematologia y Oncologia Pavlovsky
Princess Margaret Hospital
Ruijin Hospital
Faculty Hospital Brno
University Hospital
Faculty Hospital Kralovske Vinohrady
General University Hospital
University of Duisburg-Essen, Campus Essen
A.O. SS. Antonio e Biagio e Cesare Arrigo
Clinica di Ematologia Ospedali Riuniti "Umberto I"
Centro di Riferimento Oncologico - Aviano
A.O.U Policlinico Consorziale di Bari
Bari IRCCS Istituto Tumori
Ospedale Mons. Dimiccoli
Ospedale Papa Giovanni Xxiii
Sant'Orsola Malpighi
Comprensorio Sanitario di Bolzano
Spedali Civili
Asl Uoc Ematologia A Perrino
Ospedale Businco
AO Garibaldi Nesima Catalia
Ospedale S. Croce e Carle
Unità Funzionale di Ematologia AOU Careggi
U.O. Ematologia Vito Fazzi
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
SC Ematologia Azienda Ospedali Riuniti Papardo Piemonte
Istituto Scientifico San Raffaele
Milano Ieo
SC Ematologia AO Niguarda
AOU Policlinico di Modena
Ematologia Università degli Studi di Federico II
Ospedale Umberto I
Azienda Ospedaliera Universitaria
Ospedali Riuniti Villa Sofia
AOU di Parma
Fondazione IRCCS S. Matteo
S.C. Ematologia Ospedale S. Marid Della Misericordia
Ospedale Civile di Pescara
Ospedale Civico Guglielmo di Saliceto
Ospedale San Carlo di Potenza
U.O. Oncologia Ematologia Ospedale S. Maria Delle Croci
A.O. Bianchi-Melacrino-Morelli, Divisione di Ematologia
ICCRS Azienda Ospedaliera Arcipedale "Santa Maria Nuova"
Ospedale Degli Infermi
Fondazione PTV Policlinico Tor Vergata
AO San Camillo Forlanini
AOU S. Andrea Roma
Ospedale S. Eugenio
Policlinico Universitario Campus Bio-Medico
Roma Regina Elena IFO
Roma San Giovanni
Università degli Studi La Sapienza
Rozzano Humanitas
Siena
AOS Maria di Terni
AOS S. Giovanni Battista "Molinette"
Azienda Ospedaliera Citta Della Salute E Della Scienza Di Torino
Ospedale Cardinale Panico
Azienda Ospedaliera Univesritaria
Asst Settelaghi Ospedale Macchi
Oslo University Hospital
St Olavs Hospital
Warsaw Centrum Onkologi Instytucie
Istituto Portugues de Oncologia de Lisboa
Lund Universitet
IOSI
Inselspital Bern
Kantonsspital Olten
Kantonsspital
Kyiv National Cancer Institute
Basingstoke & North Hamptshire Hospital
Birmingham Heartlands Hospital
Glasgow Beatson Cancer Center
Leeds St. James's Hospital
Royal Liverpool University Hospital
Guy's & St. Thomas London
UCLH St. Thomas
Manchester The Christie NHS Foundation Trust
Newcastle Freeman Hospital
Norfolk & Norwich University Hospital
Nottingham University Hospital
General Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

observation

mediastinal irradiation

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Overall survival (OS)

OS is defined as the time from registration until death as a result of any cause until five years from registration

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)

Full Information

NCT ID

NCT01599559

First Posted

May 10, 2012

Last Updated

October 17, 2023

Sponsor

International Extranodal Lymphoma Study Group (IELSG)

1. Study Identification

Unique Protocol Identification Number

NCT01599559

Brief Title

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

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

October 2012 (Actual)

Primary Completion Date

June 17, 2022 (Actual)

Study Completion Date

December 17, 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

International Extranodal Lymphoma Study Group (IELSG)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Primary Mediastinal B-cell Lymphoma

Keywords

previously, untreated

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

540 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

observation

Arm Type

Experimental

Arm Description

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.

Arm Title

mediastinal irradiation

Arm Type

Active Comparator

Arm Description

Intervention Type

Other

Intervention Name(s)

observation

Intervention Description

observation

Intervention Type

Radiation

Intervention Name(s)

3D-Conformal Radiotherapy (3D-CRT)

Intervention Description

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

Primary Outcome Measure Information:

Title

Progression free survival (PFS)

Description

Time Frame

30 months from the randomization

Secondary Outcome Measure Information:

Title

Overall survival (OS)

Description

OS is defined as the time from registration until death as a result of any cause until five years from registration

Time Frame

5 years from registration

Title

Long term toxicity

Description

Time Frame

10 years from registration

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Overall Study Officials: