Randomized Trial of Chlorambucil Versus Chlorambucil Plus Rituximab Versus Rituximab in MALT Lymphoma
Condition: Lymphoma, Mucosa-Associated Lymphoid Tissue
MeSH terms: Lymphoma; Lymphoma, B-Cell, Marginal Zone
Intervention: chlorambucil (drug); rituximab+chlorambucil; rituximab
Intervention description: 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); rituximab 375 mg/m2 iv, d1, 8, 15, 22, 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; rituximab 375 mg/m2 iv on days 1, 8, 15, 22, 56, 84, 112, 140
Intervention MeSH terms: Rituximab; Chlorambucil
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 454.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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