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

Phase 3

Completed

• Conditions: Lymphoma, Mucosa-Associated Lymphoid Tissue
• Interventions: Drug: chlorambucil (drug); Drug: rituximab+chlorambucil; Drug: rituximab

• 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

Study Timeline

• Study Start: 2003-01
• Study First Submitted: 2005-09-13
• Study First Submitted QC: 2005-09-13
• Study First Posted: 2005-09-21
• Primary Completion: 2015-04
• Study Completion: 2016-02-17
• Status Verified: 2018-10
• Results First Submitted: 2018-10-17
• Results First Submitted QC: 2019-03-01
• Last Update Submitted: 2019-03-01
• Results First Posted: 2019-06-06
• Last Update Posted: 2019-06-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 454

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

Exclusion Criteria

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)

ACZA Campus Stuivenberg; 🇧🇪 Antwerpen, Belgium

AZ StJan; 🇧🇪 Brugge, Belgium

St Luc; 🇧🇪 Bruxelles, Belgium

ULB Hopital Erasme; 🇧🇪 Bruxelles, Belgium

CHNDRF; 🇧🇪 Charleroi, Belgium

Hospital St Joseph; 🇧🇪 Gilly, Belgium

UCL de Mont Godinne; 🇧🇪 Yvoir, Belgium

Centre Hospitalier de Blois; 🇫🇷 Blois, France

Hopital Avicenne; 🇫🇷 Bobigny, France

CHU; 🇫🇷 Nancy, France

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