Clinical trial NCT00210353: Randomized Trial of Chlorambucil Versus Chlorambucil Plus Rituximab Versus Rituximab in MALT Lymphoma
Official title: Multicenter Randomized Trial of Chlorambucil Versus Chlorambucil Plus Rituximab Versus Rituximab in Extranodal Marginal Zone B-cell Lymphoma of Mucosa Associated Lymphoid Tissue (MALT Lymphoma)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lymphoma, Mucosa-Associated Lymphoid Tissue
Lead sponsor: International Extranodal Lymphoma Study Group (IELSG)
Sponsor class: OTHER
First posted: 2005-09-21
Enrollment: 454
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: Assess the therapeutic activity and safety of the combination of Chlorambucil and Rituximab in MALT lymphomas and determine whether the addition of Rituximab to Chlorambucil will improve the outcome of MALT lymphoma in comparison to treatment with Chlorambucil alone.

In April 2006, a third arm of treatment was added to compare the antitumor activity and safety of rituximab alone vs chlorambucil alone


Eligibility criteria: Inclusion Criteria:

1. histologically proven diagnosis of CD20-positive marginal zone B-cell lymphoma of MALT type arisen at any extranodal site
2. any stage (Ann Arbor I-IV)
3. either de novo, or relapsed disease following local therapy (including surgery, radiotherapy and antibiotics for H. pylori-positive gastric lymphoma)
4. no evidence of histologic transformation to a high grade lymphoma
5. measurable or evaluable disease
6. age \> 18
7. life expectancy of at least 1 year
8. ECOG performance status 0-2
9. no prior diagnosis of neoplasm within 5 years, except cervical intraepithelial neoplasia type 1 (CIN1) or localized non-melanomatous skin cancer
10. no prior chemotherapy
11. no prior immunotherapy with any anti-CD20 monoclonal antibody
12. no prior radiotherapy in the last 6 weeks
13. no corticosteroids during the last 28 days, unless prednisone chronically administered at a dose \<20 mg/day for indications other than lymphoma or lymphoma-related symptoms
14. no evidence of clinically significant cardiac disease, as defined by history of symptomatic ventricular arrhythmias, congestive heart failure or myocardial infarction within 12 months before study entry
15. no evidence of symptomatic central nervous system (CNS) disease
16. no impairment of bone marrow function (WBC \>3.0x109/L, ANC \>1.5x109/L, PLT \>100x109/L), unless due to lymphoma involvement
17. no major impairment of renal function (serum creatinine \<1,5x upper normal) or liver function (ASAT/ALAT \<2,5 upper normal, total bilirubin \<2,5x upper normal), unless due to lymphoma involvement
18. no evidence of active opportunistic infections
19. no known HIV infection
20. no active HBV and/or HCV infection
21. no pregnant or lactating status
22. appropriate contraceptive method in women of childbearing potential or men
23. absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
24. informed consent must be given according to national/local regulations before randomization

Primary outcomes:
measure: Event-free-survival (EFS)
timeFrame: 5 years
Secondary outcomes:
measure: Complete and Partial Remission Rate - Percentage of Patients With Complete and Partial Response at the End of Treatment
timeFrame: End of treatment (after 24 weeks of therapy)
measure: Response Duration (Time to Relapse or Progression) - Percentage of Patients in Continuous Remission at Five Years From Trial Registration
timeFrame: 5 years
measure: Progression-free-survival (PFS)
timeFrame: 5 years
measure: Overall Survival
timeFrame: 5 years
Other outcomes:
Locations:
city: Antwerpen
country: Belgium
facility: ACZA Campus Stuivenberg
city: Brugge
country: Belgium
facility: AZ StJan
city: Bruxelles
country: Belgium
facility: St Luc
city: Bruxelles
country: Belgium
facility: ULB Hopital Erasme
city: Charleroi
country: Belgium
facility: CHNDRF
city: Gilly
country: Belgium
facility: Hospital St Joseph
city: Yvoir
country: Belgium
facility: UCL de Mont Godinne
city: Blois
country: France
facility: Centre Hospitalier de Blois
city: Bobigny
country: France
facility: Hopital Avicenne
city: Dijon
country: France
facility: CHU
city: Lens
country: France
facility: Centre Hospitalier
city: Lille
country: France
facility: CHRU Lille
city: Lyon
country: France
facility: Centre Hospitalier Lyon Sud
city: Lyon
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Monpellier
country: France
facility: Hopital Arnold Villeneuve
city: Nancy
country: France
facility: CHU
city: Nantes-St. Herblain
country: France
facility: Centre R. Gauducheau
city: Nantes
country: France
facility: CHU Hotel Dieu
city: Paris
country: France
facility: Hopital Henri-Mondor
city: Paris
country: France
facility: Hopital St Louis
city: Paris
country: France
facility: Necker
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Brescia
country: Italy
facility: Spedali Civili
city: Cittadella
country: Italy
facility: Azienda ULSS 15 Alta Padovana
city: Genova
country: Italy
facility: IST
city: Milano
country: Italy
facility: IEO
city: Milano
country: Italy
facility: INT
city: Milan
country: Italy
facility: Humanitas
city: Milan
country: Italy
facility: San Raffaele Hospital
city: Modena
country: Italy
facility: Policlinico
city: Piacenza
country: Italy
facility: Ospedale Civile
city: Reggio Calabria
country: Italy
facility: A.O. Bianchi-Melacrino-Morelli, Divisione di Ematologia
city: Reggio Emilia
country: Italy
facility: Arcispedale S. Maria Nuova
city: Rome
country: Italy
facility: S. Eugenio
city: Rome
country: Italy
facility: Università Cattolica Sacro Cuore
city: Rome
country: Italy
facility: Università La Sapienza
city: Sassuolo
country: Italy
facility: Sassuolo GISL
city: Siena
country: Italy
facility: AOU Senese
city: Torino
country: Italy
facility: A.O.U. San Giovanni Battista-Molinette, S.C. Ematologia 2
city: Trani
country: Italy
facility: Trani GISL
city: Varese
country: Italy
facility: Ospedale di Circolo Fondazione Macchi
city: Verona
country: Italy
facility: Policlinico GB Rossi
city: Barcelona
country: Spain
facility: Clinic Hospital Universitari
city: Barcelona
country: Spain
facility: Hopital Mataro'
city: Barcelona
country: Spain
facility: Hopital Santa Creu i Sant Pau
city: Salamanca
country: Spain
facility: University Hospital
city: Tarragona
country: Spain
facility: Joan XXIII
city: Bellinzona
country: Switzerland
facility: IOSI
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
city: Birmingham
country: United Kingdom
facility: Heartlands
city: Blackpool
country: United Kingdom
facility: Victoria Hospital
city: Cornwall
country: United Kingdom
facility: Royal Cornwall Hospital
city: Dartford
country: United Kingdom
facility: Darent Valley Hospital
city: Devon
country: United Kingdom
facility: Royal Devon &Exeter Healtcare NHS Trust
city: Dudley
country: United Kingdom
facility: Russels Hall Hospital
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
city: Gillingham
country: United Kingdom
facility: Medway Hospital
city: Inverness
country: United Kingdom
facility: Raigmore Hospital
city: Liverpool
country: United Kingdom
facility: Liverpool Royal Hospital
city: Liverpool
country: United Kingdom
facility: University Hospital Aintree
city: London
country: United Kingdom
facility: Barts & the London NHS Trust
city: London
country: United Kingdom
facility: Royal Marsden NHS Foundation Trust
city: London
country: United Kingdom
facility: St Georges
city: Manchester
country: United Kingdom
facility: Christie Hospital
city: Middlesex
country: United Kingdom
facility: Mount Vernon Hospital
city: Norfolk
country: United Kingdom
facility: James Paget Hospital
city: Norfolk
country: United Kingdom
facility: Queen Elisabeth
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
city: Oxford
country: United Kingdom
facility: John Radcliffe
city: Saint Leonard On Sea
country: United Kingdom
facility: Conquest Hospital
city: Sheffield
country: United Kingdom
facility: Weston Park
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
city: West Bromwich
country: United Kingdom
facility: Sandwell General Hospital
city: Worcester
country: United Kingdom
facility: Worchestershire Acute Hospital NHS Trust
Study officials:
affiliation: International Extranodal Lymphoma Study Group/Oncology Institute of Southern Switzerland. Bellinzona
name: Emanuele Zucca, MD
role: STUDY_CHAIR
affiliation: Clinic Hospital Universitari, Hematology. Barcelona
name: Emilio Montserrat, MD
role: STUDY_CHAIR
affiliation: Centre Hospitalier Lyon Sud, Hematology. Lyon
name: Catherine Thieblemont, MD
role: STUDY_CHAIR
affiliation: Hemato-oncology. European Oncology Institute. Milan
name: Giovanni Martinelli, MD
role: STUDY_CHAIR
affiliation: Oncology Unit. Southampton General Hospital. Southampton
name: Peter Johnson, MD
role: STUDY_CHAIR
affiliation: Hematology. Università La Sapienza. Roma
name: Maurizio Martelli, MD
role: STUDY_CHAIR
References:
citation: Zucca E, Conconi A, Laszlo D, Lopez-Guillermo A, Bouabdallah R, Coiffier B, Sebban C, Jardin F, Vitolo U, Morschhauser F, Pileri SA, Copie-Bergman C, Campo E, Jack A, Floriani I, Johnson P, Martelli M, Cavalli F, Martinelli G, Thieblemont C. Addition of rituximab to chlorambucil produces superior event-free survival in the treatment of patients with extranodal marginal-zone B-cell lymphoma: 5-year analysis of the IELSG-19 Randomized Study. J Clin Oncol. 2013 Feb 10;31(5):565-72. doi: 10.1200/JCO.2011.40.6272. Epub 2013 Jan 7.