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

March 1, 2019 updated by: International Extranodal Lymphoma Study Group (IELSG)

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)

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

454

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Antwerpen, Belgium
        • ACZA Campus Stuivenberg
      • Brugge, Belgium
        • AZ StJan
      • Bruxelles, Belgium
        • ULB Hôpital Erasme
      • Bruxelles, Belgium
        • St Luc
      • Charleroi, Belgium
        • CHNDRF
      • Gilly, Belgium
        • Hospital St Joseph
      • Yvoir, Belgium
        • UCL de Mont Godinne
  • France
      • Blois, France
        • Centre Hospitalier de Blois
      • Bobigny, France
        • Hôpital Avicenne
      • Dijon, France
        • CHU
      • Lens, France
        • Centre Hospitalier
      • Lille, France
        • CHRU Lille
      • Lyon, France
        • Centre Leon Berard
      • Lyon, France
        • Centre Hospitalier Lyon Sud
      • Marseille, France
        • Institut Paoli Calmettes
      • Monpellier, France
        • Hopital Arnold Villeneuve
      • Nancy, France
        • CHU
      • Nantes, France
        • Chu Hotel Dieu
      • Nantes-St. Herblain, France
        • Centre R. Gauducheau
      • Paris, France
        • Hopital St Louis
      • Paris, France
        • NECKER
      • Paris, France
        • Hopital Henri-Mondor
      • Rouen, France
        • Centre Henri Becquerel
  • Italy
      • Brescia, Italy
        • Spedali Civili
      • Cittadella, Italy
        • Azienda ULSS 15 Alta Padovana
      • Genova, Italy
        • IST
      • Milan, Italy
        • Humanitas
      • Milan, Italy
        • San Raffaele Hospital
      • Milano, Italy
        • IEO
      • Milano, Italy
        • INT
      • Modena, Italy
        • Policlinico
      • Piacenza, Italy
        • Ospedale Civile
      • Reggio Calabria, Italy
        • A.O. Bianchi-Melacrino-Morelli, Divisione di Ematologia
      • Reggio Emilia, Italy
        • Arcispedale S. Maria Nuova
      • Rome, Italy
        • Università La Sapienza
      • Rome, Italy
        • Universita Cattolica Sacro Cuore
      • Rome, Italy
        • S. Eugenio
      • Sassuolo, Italy
        • Sassuolo GISL
      • Siena, Italy
        • AOU Senese
      • Torino, Italy, 10134
        • A.O.U. San Giovanni Battista-Molinette, S.C. Ematologia 2
      • Trani, Italy
        • Trani GISL
      • Varese, Italy
        • Ospedale di Circolo Fondazione Macchi
      • Verona, Italy
        • Policlinico GB Rossi
  • Spain
      • Barcelona, Spain
        • Clinic Hospital Universitari
      • Barcelona, Spain
        • Hopital Mataro'
      • Barcelona, Spain
        • Hopital Santa Creu i Sant Pau
      • Salamanca, Spain
        • University Hospital
      • Tarragona, Spain
        • Joan XXIII
  • Switzerland
      • Bellinzona, Switzerland, 6500
        • IOSI
  • United Kingdom
      • Aberdeen, United Kingdom
        • Aberdeen Royal Infirmary
      • Birmingham, United Kingdom
        • Heartlands
      • Blackpool, United Kingdom
        • Victoria Hospital
      • Cornwall, United Kingdom
        • Royal Cornwall Hospital
      • Dartford, United Kingdom
        • Darent Valley Hospital
      • Devon, United Kingdom
        • Royal Devon &Exeter Healtcare NHS Trust
      • Dudley, United Kingdom
        • Russels Hall Hospital
      • Edinburgh, United Kingdom
        • Western General Hospital
      • Gillingham, United Kingdom
        • Medway Hospital
      • Inverness, United Kingdom
        • Raigmore Hospital
      • Liverpool, United Kingdom
        • University Hospital Aintree
      • Liverpool, United Kingdom
        • Liverpool Royal Hospital
      • London, United Kingdom
        • Barts & The London NHS Trust
      • London, United Kingdom
        • Royal Marsden NHS Foundation Trust
      • London, United Kingdom
        • St Georges
      • Manchester, United Kingdom
        • Christie Hospital
      • Middlesex, United Kingdom
        • Mount Vernon Hospital
      • Norfolk, United Kingdom
        • James Paget Hospital
      • Norfolk, United Kingdom
        • Queen Elisabeth
      • Nottingham, United Kingdom
        • Nottingham City Hospital
      • Oxford, United Kingdom
        • John Radcliffe
      • Saint Leonard On Sea, United Kingdom
        • Conquest Hospital
      • Sheffield, United Kingdom
        • Weston Park
      • Southampton, United Kingdom
        • Southampton General Hospital
      • West Bromwich, United Kingdom
        • Sandwell General Hospital
      • Worcester, United Kingdom
        • Worchestershire Acute Hospital NHS Trust

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: ARM A
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)
Drug: 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)
Experimental: ARM B
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
Drug: rituximab+chlorambucil
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
Experimental: ARM C (Since April 2006)
rituximab 375 mg/m2 iv on days 1, 8, 15, 22, 56, 84, 112, 140
Drug: rituximab
rituximab 375 mg/m2 iv on days 1, 8, 15, 22, 56, 84, 112, 140

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Event-free-survival (EFS)
Time Frame: 5 years
Percentage of patients without events (failure of treatment or Death from any cause) after 5 years from trial registration
5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete and Partial Remission Rate - Percentage of Patients With Complete and Partial Response at the End of Treatment
Time Frame: 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.
End of treatment (after 24 weeks of therapy)
Response Duration (Time to Relapse or Progression) - Percentage of Patients in Continuous Remission at Five Years From Trial Registration
Time Frame: 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).
5 years
Progression-free-survival (PFS)
Time Frame: 5 years
Percentage of patients without disease progression after 5 years from trial registration
5 years
Overall Survival
Time Frame: 5 years
Percentage of patients alive after 5 years from trial registration
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

International Extranodal Lymphoma Study Group (IELSG)

Investigators

  • Study Chair: Emanuele Zucca, MD, International Extranodal Lymphoma Study Group/Oncology Institute of Southern Switzerland. Bellinzona
  • Study Chair: Emilio Montserrat, MD, Clinic Hospital Universitari, Hematology. Barcelona
  • Study Chair: Catherine Thieblemont, MD, Centre Hospitalier Lyon Sud, Hematology. Lyon
  • Study Chair: Giovanni Martinelli, MD, Hemato-oncology. European Oncology Institute. Milan
  • Study Chair: Peter Johnson, MD, Oncology Unit. Southampton General Hospital. Southampton
  • Study Chair: Maurizio Martelli, MD, Hematology. Università La Sapienza. Roma

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2003

Primary Completion (Actual)

April 1, 2015

Study Completion (Actual)

February 17, 2016

Study Registration Dates

First Submitted

September 13, 2005

First Submitted That Met QC Criteria

September 13, 2005

First Posted (Estimate)

September 21, 2005

Study Record Updates

Last Update Posted (Actual)

June 6, 2019

Last Update Submitted That Met QC Criteria

March 1, 2019

Last Verified

October 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IELSG19

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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