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
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trial is to test whether radiation therapy is really necessary in patients where PET/CT has shown that the tumor is no longer active.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 |
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N/A |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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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
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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.
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Outcome Measures
Primary Outcome Measures
- 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
- Overall survival (OS) [5 years from registration]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Previously untreated primary mediastinal diffuse large B-cell lymphoma, CD20 positive.
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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.
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No evidence of extranodal disease outside the chest including spleen and bone marrow.
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Age at least 18 years.
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Fit to receive chemotherapy and radiotherapy with curative intent.
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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).
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At least 6 courses of Rituximab should be administered
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Able and willing to give informed consent, and to undergo staging including PET scanning
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Willingness to comply with an appropriate contraceptive method in women of childbearing potential or men.
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Histological diagnostic material available for review.
Exclusion Criteria:
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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.
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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.
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Known HIV-positive serology.
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Pregnant or lactating women.
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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 | |
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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.- IELSG37