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

Primary Purpose

Lymphoma, Mucosa-Associated Lymphoid Tissue

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

chlorambucil (drug)

rituximab+chlorambucil

rituximab

About this trial

This is an interventional treatment trial for Lymphoma, Mucosa-Associated Lymphoid Tissue

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Experimental

Arm Label

ARM A

ARM B

ARM C (Since April 2006)

Arm 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, 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

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

Outcomes

Primary Outcome Measures

Event-free-survival (EFS)

Percentage of patients without events (failure of treatment or Death from any cause) after 5 years from trial registration

Secondary Outcome Measures

Complete and Partial Remission Rate - Percentage of Patients With Complete and Partial Response at the End of Treatment

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

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)

Percentage of patients without disease progression after 5 years from trial registration

Overall Survival

Percentage of patients alive after 5 years from trial registration

Full Information

NCT ID

NCT00210353

First Posted

September 13, 2005

Last Updated

March 1, 2019

Sponsor

International Extranodal Lymphoma Study Group (IELSG)

1. Study Identification

Unique Protocol Identification Number

NCT00210353

Brief Title

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

Official Title

Multicenter Randomized Trial of Chlorambucil Versus Chlorambucil Plus Rituximab Versus Rituximab in Extranodal Marginal Zone B-cell Lymphoma of Mucosa Associated Lymphoid Tissue (MALT Lymphoma)

Study Type

Interventional

2. Study Status

Record Verification Date

October 2018

Overall Recruitment Status

Completed

Study Start Date

January 2003 (undefined)

Primary Completion Date

April 2015 (Actual)

Study Completion Date

February 17, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

International Extranodal Lymphoma Study Group (IELSG)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Lymphoma, Mucosa-Associated Lymphoid Tissue

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

454 (Actual)

8. Arms, Groups, and Interventions

Arm Title

ARM A

Arm Type

Active Comparator

Arm 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)

Arm Title

ARM B

Arm Type

Experimental

Arm Description

Arm Title

ARM C (Since April 2006)

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

chlorambucil (drug)

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)

Intervention Type

Drug

Intervention Name(s)

rituximab+chlorambucil

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

rituximab

Intervention Description

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

Primary Outcome Measure Information:

Title

Event-free-survival (EFS)

Description

Percentage of patients without events (failure of treatment or Death from any cause) after 5 years from trial registration

Time Frame

5 years

Secondary Outcome Measure Information:

Title

Complete and Partial Remission Rate - Percentage of Patients With Complete and Partial Response at the End of Treatment

Description

Time Frame

End of treatment (after 24 weeks of therapy)

Title

Response Duration (Time to Relapse or Progression) - Percentage of Patients in Continuous Remission at Five Years From Trial Registration

Description

Time Frame

5 years

Title

Progression-free-survival (PFS)

Description

Percentage of patients without disease progression after 5 years from trial registration

Time Frame

5 years

Title

Overall Survival

Description

Percentage of patients alive after 5 years from trial registration

Time Frame

5 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Overall Study Officials: