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

International Extranodal Lymphoma Study Group (IELSG)

Status and phase: Completed; Phase 3

Conditions: Lymphoma, Mucosa-Associated Lymphoid Tissue

Treatments: Drug: rituximab; Drug: chlorambucil (drug); Drug: rituximab+chlorambucil

Study type: Interventional

Funder types: Other

Identifiers

NCT00210353

IELSG19

Details and patient eligibility

About

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

Enrollment: 454 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

454 participants in 3 patient groups

ARM A

Active Comparator group

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)

Treatment:

Drug: chlorambucil (drug)

ARM B

Experimental group

Description:

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

Treatment:

Drug: rituximab+chlorambucil

ARM C (Since April 2006)

Experimental group

Description:

rituximab 375 mg/m2 iv on days 1, 8, 15, 22, 56, 84, 112, 140

Treatment:

Drug: rituximab