Randomized Trial of Chlorambucil Versus Chlorambucil Plus Rituximab Versus Rituximab in MALT Lymphoma
- Conditions
- Lymphoma, Mucosa-Associated Lymphoid Tissue
- Interventions
- Registration Number
- NCT00210353
- Lead Sponsor
- International Extranodal Lymphoma Study Group (IELSG)
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 454
- histologically proven diagnosis of CD20-positive marginal zone B-cell lymphoma of MALT type arisen at any extranodal site
- any stage (Ann Arbor I-IV)
- either de novo, or relapsed disease following local therapy (including surgery, radiotherapy and antibiotics for H. pylori-positive gastric lymphoma)
- no evidence of histologic transformation to a high grade lymphoma
- measurable or evaluable disease
- age > 18
- life expectancy of at least 1 year
- ECOG performance status 0-2
- no prior diagnosis of neoplasm within 5 years, except cervical intraepithelial neoplasia type 1 (CIN1) or localized non-melanomatous skin cancer
- no prior chemotherapy
- no prior immunotherapy with any anti-CD20 monoclonal antibody
- no prior radiotherapy in the last 6 weeks
- 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
- 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
- no evidence of symptomatic central nervous system (CNS) disease
- no impairment of bone marrow function (WBC >3.0x109/L, ANC >1.5x109/L, PLT >100x109/L), unless due to lymphoma involvement
- 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
- no evidence of active opportunistic infections
- no known HIV infection
- no active HBV and/or HCV infection
- no pregnant or lactating status
- appropriate contraceptive method in women of childbearing potential or men
- 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
- informed consent must be given according to national/local regulations before randomization
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ARM A chlorambucil (drug) chlorambucil 6 mg/m2 daily during the first 6 weeks of treatment; two weeks rest; chlorambucil 6 mg/m2 daily during the first two of a four weeks cycles (total of 4 cycles) ARM B rituximab+chlorambucil rituximab 375 mg/m2 iv, d1, d8, d15, d22 chlorambucil 6 mg/m2 os, daily during the first 6 weeks of treatment two weeks rest chlorambucil 6 mg/m2 os daily during the first two of a four weeks cycles (total of 4 cycles) rituximab 375 mg/m2 iv at day 1 of each cycle ARM C (Since April 2006) rituximab rituximab 375 mg/m2 iv on days 1, 8, 15, 22, 56, 84, 112, 140
- Primary Outcome Measures
Name Time Method Event-free-survival (EFS) 5 years Percentage of patients without events (failure of treatment or Death from any cause) after 5 years from trial registration
- Secondary Outcome Measures
Name Time Method Complete and Partial Remission Rate - Percentage of Patients With Complete and Partial Response at the End of Treatment End of treatment (after 24 weeks of therapy) Response criteria were defined according to the NCI standardized response criteria for non-Hodgkin's lymphoma.
Complete response. Disappearance of all detectable clinical and radiographic evidence of disease, disappearance of all disease-related symptoms, if present before therapy, and normalization of those biochemical abnormalities definitely assignable to NHL. Regression of all lymph nodes and nodal masses to normal (≤ 1.5 cm in their greatest transverse diameter for nodes \> 1.5 cm before therapy and to ≤ 1 cm for nodes that were 1.1-1.5 cm. Regression by more than 75% in the sum of the products of the greatest diameters).
Partial response. Decrease by at least 50% in SPD of the six largest measurable lesions. It is not necessary for all lesions to have regressed to qualify for partial response, but no lesion should have progressed and no new lesion should appear.
For primary gastric sites, response was based on GELA histologic grading system.Response Duration (Time to Relapse or Progression) - Percentage of Patients in Continuous Remission at Five Years From Trial Registration 5 years Response criteria were defined according to the NCI standardized response criteria for non-Hodgkin's lymphoma.
Complete response (CR). Disappearance of all detectable clinical and radiographic evidence of disease, disappearance of all disease-related symptoms, if present before therapy, and normalization of those biochemical abnormalities definitely assignable to NHL. Regression of all lymph nodes and nodal masses to normal (≤ 1.5 cm in their greatest transverse diameter for nodes \> 1.5 cm before therapy and to ≤ 1 cm for nodes that were 1.1-1.5 cm. Regression by more than 75% in the sum of the products of the greatest diameters).Progression-free-survival (PFS) 5 years Percentage of patients without disease progression after 5 years from trial registration
Overall Survival 5 years Percentage of patients alive after 5 years from trial registration
Trial Locations
- Locations (74)
IST
🇮🇹Genova, Italy
Ospedale di Circolo Fondazione Macchi
🇮🇹Varese, Italy
Russels Hall Hospital
🇬🇧Dudley, United Kingdom
Hopital Avicenne
🇫🇷Bobigny, France
Centre Hospitalier de Blois
🇫🇷Blois, France
Centre Leon Berard
🇫🇷Lyon, France
A.O. Bianchi-Melacrino-Morelli, Divisione di Ematologia
🇮🇹Reggio Calabria, Italy
Heartlands
🇬🇧Birmingham, United Kingdom
A.O.U. San Giovanni Battista-Molinette, S.C. Ematologia 2
🇮🇹Torino, Italy
Darent Valley Hospital
🇬🇧Dartford, United Kingdom
Aberdeen Royal Infirmary
🇬🇧Aberdeen, United Kingdom
Azienda ULSS 15 Alta Padovana
🇮🇹Cittadella, Italy
Victoria Hospital
🇬🇧Blackpool, United Kingdom
Humanitas
🇮🇹Milan, Italy
Joan XXIII
🇪🇸Tarragona, Spain
Hopital Henri-Mondor
🇫🇷Paris, France
Ospedale Civile
🇮🇹Piacenza, Italy
Università Cattolica Sacro Cuore
🇮🇹Rome, Italy
University Hospital
🇪🇸Salamanca, Spain
Hopital St Louis
🇫🇷Paris, France
Hopital Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Royal Devon &Exeter Healtcare NHS Trust
🇬🇧Devon, United Kingdom
Mount Vernon Hospital
🇬🇧Middlesex, United Kingdom
Weston Park
🇬🇧Sheffield, United Kingdom
Western General Hospital
🇬🇧Edinburgh, United Kingdom
John Radcliffe
🇬🇧Oxford, United Kingdom
Centre R. Gauducheau
🇫🇷Nantes-St. Herblain, France
Spedali Civili
🇮🇹Brescia, Italy
IEO
🇮🇹Milano, Italy
Barts & the London NHS Trust
🇬🇧London, United Kingdom
Christie Hospital
🇬🇧Manchester, United Kingdom
Sandwell General Hospital
🇬🇧West Bromwich, United Kingdom
INT
🇮🇹Milano, Italy
Policlinico
🇮🇹Modena, Italy
Arcispedale S. Maria Nuova
🇮🇹Reggio Emilia, Italy
S. Eugenio
🇮🇹Rome, Italy
Università La Sapienza
🇮🇹Rome, Italy
Trani GISL
🇮🇹Trani, Italy
UCL de Mont Godinne
🇧🇪Yvoir, Belgium
ACZA Campus Stuivenberg
🇧🇪Antwerpen, Belgium
Hospital St Joseph
🇧🇪Gilly, Belgium
St Georges
🇬🇧London, United Kingdom
Raigmore Hospital
🇬🇧Inverness, United Kingdom
James Paget Hospital
🇬🇧Norfolk, United Kingdom
Queen Elisabeth
🇬🇧Norfolk, United Kingdom
CHU
🇫🇷Nancy, France
Centre Hospitalier
🇫🇷Lens, France
CHRU Lille
🇫🇷Lille, France
Centre Hospitalier Lyon Sud
🇫🇷Lyon, France
Institut Paoli Calmettes
🇫🇷Marseille, France
Necker
🇫🇷Paris, France
Centre Henri Becquerel
🇫🇷Rouen, France
St Luc
🇧🇪Bruxelles, Belgium
AZ StJan
🇧🇪Brugge, Belgium
ULB Hopital Erasme
🇧🇪Bruxelles, Belgium
CHNDRF
🇧🇪Charleroi, Belgium
CHU Hotel Dieu
🇫🇷Nantes, France
Hopital Arnold Villeneuve
🇫🇷Monpellier, France
San Raffaele Hospital
🇮🇹Milan, Italy
Sassuolo GISL
🇮🇹Sassuolo, Italy
AOU Senese
🇮🇹Siena, Italy
Clinic Hospital Universitari
🇪🇸Barcelona, Spain
Policlinico GB Rossi
🇮🇹Verona, Italy
IOSI
🇨🇭Bellinzona, Switzerland
Hopital Mataro'
🇪🇸Barcelona, Spain
Royal Cornwall Hospital
🇬🇧Cornwall, United Kingdom
Medway Hospital
🇬🇧Gillingham, United Kingdom
Liverpool Royal Hospital
🇬🇧Liverpool, United Kingdom
University Hospital Aintree
🇬🇧Liverpool, United Kingdom
Nottingham City Hospital
🇬🇧Nottingham, United Kingdom
Worchestershire Acute Hospital NHS Trust
🇬🇧Worcester, United Kingdom
Conquest Hospital
🇬🇧Saint Leonard On Sea, United Kingdom
Southampton General Hospital
🇬🇧Southampton, United Kingdom
Royal Marsden NHS Foundation Trust
🇬🇧London, United Kingdom