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

Sponsor
International Extranodal Lymphoma Study Group (IELSG) (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT01599559
Collaborator
(none)
540
85
2
151
6.4
0

Study Details

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trial is to test whether radiation therapy is really necessary in patients where PET/CT has shown that the tumor is no longer active.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

Condition or Disease Intervention/Treatment Phase
  • Other: observation
  • Radiation: 3D-Conformal Radiotherapy (3D-CRT)
N/A

Study Design

Study Type:
Interventional
Anticipated Enrollment :
540 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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)
Actual Study Start Date :
Oct 1, 2012
Anticipated Primary Completion Date :
Dec 1, 2022
Anticipated Study Completion Date :
May 1, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: 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.

Other: observation
observation

Active Comparator: 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.

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

Outcome Measures

Primary Outcome Measures

  1. Progression free survival (PFS) [30 months from the randomization]

    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

  1. Overall survival (OS) [5 years from registration]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Norton Cancer Institute Louisville Kentucky United States
2 Mayo Clinil Rocheser Rochester Minnesota United States 55905
3 MD Anderson Cancer Center Houston Texas United States
4 Centro de Hematologia y Oncologia Pavlovsky Buenos Aires Argentina
5 Princess Margaret Hospital Toronto Canada
6 Ruijin Hospital Shanghai China
7 Faculty Hospital Brno Brno Czechia
8 University Hospital Hradec Kralove Czechia
9 Faculty Hospital Kralovske Vinohrady Prague Czechia
10 General University Hospital Prague Czechia
11 University of Duisburg-Essen, Campus Essen Essen Germany
12 A.O. SS. Antonio e Biagio e Cesare Arrigo Alessandria Italy
13 Clinica di Ematologia Ospedali Riuniti "Umberto I" Ancona Italy
14 Centro di Riferimento Oncologico - Aviano Aviano Italy
15 A.O.U Policlinico Consorziale di Bari Bari Italy
16 Bari IRCCS Istituto Tumori Bari Italy
17 Ospedale Mons. Dimiccoli Barletta Italy
18 Ospedale Papa Giovanni Xxiii Bergamo Italy
19 Sant'Orsola Malpighi Bologna Italy
20 Comprensorio Sanitario di Bolzano Bolzano Italy
21 Spedali Civili Brescia Italy
22 Asl Uoc Ematologia A Perrino Brindisi Italy
23 Ospedale Businco Cagliari Italy
24 AO Garibaldi Nesima Catalia Catania Italy
25 Ospedale S. Croce e Carle Cuneo Italy
26 Unità Funzionale di Ematologia AOU Careggi Firenze Italy
27 U.O. Ematologia Vito Fazzi Lecce Italy
28 Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori Meldola Italy
29 SC Ematologia Azienda Ospedali Riuniti Papardo Piemonte Messina Italy
30 Istituto Scientifico San Raffaele Milano Italy
31 Milano Ieo Milano Italy
32 SC Ematologia AO Niguarda Milano Italy
33 AOU Policlinico di Modena Modena Italy
34 Ematologia Università degli Studi di Federico II Napoli Italy
35 Ospedale Umberto I Nocera Italy
36 Azienda Ospedaliera Universitaria Padova Italy
37 Ospedali Riuniti Villa Sofia Palermo Italy
38 AOU di Parma Parma Italy
39 Fondazione IRCCS S. Matteo Pavia Italy
40 S.C. Ematologia Ospedale S. Marid Della Misericordia Perugia Italy
41 Ospedale Civile di Pescara Pescara Italy
42 Ospedale Civico Guglielmo di Saliceto Piacenza Italy
43 Ospedale San Carlo di Potenza Potenza Italy
44 U.O. Oncologia Ematologia Ospedale S. Maria Delle Croci Ravenna Italy
45 A.O. Bianchi-Melacrino-Morelli, Divisione di Ematologia Reggio Calabria Italy
46 ICCRS Azienda Ospedaliera Arcipedale "Santa Maria Nuova" Reggio Emilia Italy
47 Ospedale Degli Infermi Rimini Italy
48 Fondazione PTV Policlinico Tor Vergata Roma Italy 00133
49 AO San Camillo Forlanini Roma Italy
50 AOU S. Andrea Roma Roma Italy
51 Ospedale S. Eugenio Roma Italy
52 Policlinico Universitario Campus Bio-Medico Roma Italy
53 Roma Regina Elena IFO Roma Italy
54 Roma San Giovanni Roma Italy
55 Università degli Studi La Sapienza Roma Italy
56 Rozzano Humanitas Rozzano Italy
57 Siena Siena Italy
58 AOS Maria di Terni Terni Italy
59 AOS S. Giovanni Battista "Molinette" Torino Italy
60 Azienda Ospedaliera Citta Della Salute E Della Scienza Di Torino Torino Italy
61 Ospedale Cardinale Panico Tricase Italy
62 Azienda Ospedaliera Univesritaria Udine Italy
63 Asst Settelaghi Ospedale Macchi Varese Italy
64 Oslo University Hospital Oslo Norway
65 St Olavs Hospital Trondheim Norway
66 Warsaw Centrum Onkologi Instytucie Warsaw Poland
67 Istituto Portugues de Oncologia de Lisboa Lisboa Portugal
68 Lund Universitet Lund Sweden
69 IOSI Bellinzona Switzerland 6500
70 Inselspital Bern Bern Switzerland
71 Kantonsspital Olten Olten Switzerland
72 Kantonsspital St Gallen Switzerland
73 Kyiv National Cancer Institute Kiev Ukraine
74 Basingstoke & North Hamptshire Hospital Basingstoke United Kingdom
75 Birmingham Heartlands Hospital Birmingham United Kingdom
76 Glasgow Beatson Cancer Center Glasgow United Kingdom
77 Leeds St. James's Hospital Leeds United Kingdom
78 Royal Liverpool University Hospital Liverpool United Kingdom
79 Guy's & St. Thomas London London United Kingdom
80 UCLH St. Thomas London United Kingdom
81 Manchester The Christie NHS Foundation Trust Manchester United Kingdom
82 Newcastle Freeman Hospital Newcastle United Kingdom
83 Norfolk & Norwich University Hospital Norfolk United Kingdom
84 Nottingham University Hospital Nottingham United Kingdom
85 General Hospital Southampton United Kingdom

Sponsors and Collaborators

  • International Extranodal Lymphoma Study Group (IELSG)

Investigators

  • Study Chair: 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 Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
International Extranodal Lymphoma Study Group (IELSG)
ClinicalTrials.gov Identifier:
NCT01599559
Other Study ID Numbers:
  • IELSG37
First Posted:
May 16, 2012
Last Update Posted:
Aug 18, 2022
Last Verified:
Aug 1, 2022
Keywords provided by International Extranodal Lymphoma Study Group (IELSG)
Additional relevant MeSH terms:

Study Results

No Results Posted as of Aug 18, 2022