Randomized Trial of Chlorambucil Versus Chlorambucil Plus Rituximab Versus Rituximab in MALT Lymphoma

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