AzTrials
AzTrials

Lymphoma, Mucosa-Associated Lymphoid TissuePhase 3NCT00210353

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

A Phase 3 study testing chlorambucil (drug), rituximab+chlorambucil and rituximab in people with Lymphoma, Mucosa-Associated Lymphoid Tissue, run by International Extranodal Lymphoma Study Group (IELSG) at 75 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
chlorambucil (drug), rituximab+chlorambucil and rituximab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
454 participants
Where
75 sitesin 6 countries
Study dates
Jan 2003to 17 Feb 2016
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 24Show fewer
  • 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

Who cannot join

None listed.

Trial locations and contacts

75 sites in 6 countries.

75 sites in 6 countries

United Kingdom26 sites

  • Aberdeen Royal Infirmary

    Aberdeen

  • Heartlands

    Birmingham

  • Victoria Hospital

    Blackpool

  • Royal Cornwall Hospital

    Cornwall

  • Darent Valley Hospital

    Dartford

  • Royal Devon &Exeter Healtcare NHS Trust

    Devon

  • Russels Hall Hospital

    Dudley

  • Western General Hospital

    Edinburgh

  • Medway Hospital

    Gillingham

  • Raigmore Hospital

    Inverness

  • Liverpool Royal Hospital

    Liverpool

  • University Hospital Aintree

    Liverpool

  • Barts & the London NHS Trust

    London

  • Royal Marsden NHS Foundation Trust

    London

  • St Georges

    London

  • Christie Hospital

    Manchester

  • Mount Vernon Hospital

    Middlesex

  • James Paget Hospital

    Norfolk

  • Queen Elisabeth

    Norfolk

  • Nottingham City Hospital

    Nottingham

  • John Radcliffe

    Oxford

  • Conquest Hospital

    Saint Leonard on Sea

  • Weston Park

    Sheffield

  • Southampton General Hospital

    Southampton

  • Sandwell General Hospital

    West Bromwich

  • Worchestershire Acute Hospital NHS Trust

    Worcester

Other trials in United Kingdom

Italy20 sites

  • Spedali Civili

    Brescia

  • Azienda ULSS 15 Alta Padovana

    Cittadella

  • IST

    Genova

  • Humanitas

    Milan

  • San Raffaele Hospital

    Milan

  • IEO

    Milan

  • INT

    Milan

  • Policlinico

    Modena

  • Ospedale Civile

    Piacenza

  • A.O. Bianchi-Melacrino-Morelli, Divisione di Ematologia

    Reggio Calabria

  • Arcispedale S. Maria Nuova

    Reggio Emilia

  • S. Eugenio

    Rome

  • Università Cattolica Sacro Cuore

    Rome

  • Università La Sapienza

    Rome

  • Sassuolo GISL

    Sassuolo

  • AOU Senese

    Siena

  • A.O.U. San Giovanni Battista-Molinette, S.C. Ematologia 2

    Torino, 10134

  • Trani GISL

    Trani

  • Ospedale di Circolo Fondazione Macchi

    Varese

  • Policlinico GB Rossi

    Verona

Other trials in Italy

France16 sites

  • Centre Hospitalier de Blois

    Blois

  • Hopital Avicenne

    Bobigny

  • CHU

    Dijon

  • Centre Hospitalier

    Lens

  • CHRU Lille

    Lille

  • Centre Hospitalier Lyon Sud

    Lyon

  • Centre Leon Berard

    Lyon

  • Institut Paoli Calmettes

    Marseille

  • Hopital Arnold Villeneuve

    Monpellier

  • CHU

    Nancy

  • CHU Hotel Dieu

    Nantes

  • Centre R. Gauducheau

    Nantes-St. Herblain

  • Hopital Henri-Mondor

    Paris

  • Hopital St Louis

    Paris

  • Necker

    Paris

  • Centre Henri Becquerel

    Rouen

Other trials in France

Belgium7 sites

  • ACZA Campus Stuivenberg

    Antwerp

  • AZ StJan

    Bruges

  • St Luc

    Brussels

  • ULB Hopital Erasme

    Brussels

  • CHNDRF

    Charleroi

  • Hospital St Joseph

    Gilly

  • UCL de Mont Godinne

    Yvoir

Other trials in Belgium

Spain5 sites

  • Clinic Hospital Universitari

    Barcelona

  • Hopital Mataro'

    Barcelona

  • Hopital Santa Creu i Sant Pau

    Barcelona

  • University Hospital

    Salamanca

  • Joan XXIII

    Tarragona

Other trials in Spain

Switzerland1 site

  • IOSI

    Bellinzona, 6500

Other trials in Switzerland

About this study

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)

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

Being tested
chlorambucil (drug), rituximab+chlorambucil, rituximab
Medical subject headings
Lymphoma, B-Cell, Marginal Zone

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • chlorambucil (drug)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)

  • rituximab+chlorambucilDrug

    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

  • rituximabDrug

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

Study groups in NCT00210353
Study groupRoleWhat they receive
ARM AActive comparatorchlorambucil 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)
Receives: Drug: chlorambucil (drug)
ARM BExperimentalrituximab 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
Receives: Drug: rituximab+chlorambucil
ARM C (Since April 2006)Experimentalrituximab 375 mg/m2 iv on days 1, 8, 15, 22, 56, 84, 112, 140
Receives: Drug: rituximab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Event-free-survival (EFS)

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

    Measured: 5 years

Secondary outcomes (4)

  1. 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.

    Measured: End of treatment (after 24 weeks of therapy)

  2. 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).

    Measured: 5 years

  3. Progression-free-survival (PFS)

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

    Measured: 5 years

  4. Overall Survival

    Percentage of patients alive after 5 years from trial registration

    Measured: 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Sep 2005 (estimated)
  2. Study startJan 2003
  3. Primary completionApr 2015
  4. Study completion17 Feb 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
454 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00210353
Sponsor's protocol ID
IELSG19
Status last verified
Oct 2018
First submitted
13 Sep 2005
Last updated
6 Jun 2019
Data monitoring committee
Yes

Publications

  • Bommier C, Zucca E, Chevret S, Conconi A, Nowakowski G, Maurer MJ, Cerhan JR, Thieblemont C, Lambert J. Early complete response as a validated surrogate marker in extranodal marginal zone lymphoma systemic therapy. Blood. 2024 Feb 1;143(5):422-428. doi: 10.1182/blood.2023020984.

    PubMed 37801707

  • Zucca E, Conconi A, Laszlo D, Lopez-Guillermo A, Bouabdallah R, Coiffier B, Sebban C, Jardin F, Vitolo U, Morschhauser F, Pileri SA, Copie-Bergman C, Campo E, Jack A, Floriani I, Johnson P, Martelli M, Cavalli F, Martinelli G, Thieblemont C. Addition of rituximab to chlorambucil produces superior event-free survival in the treatment of patients with extranodal marginal-zone B-cell lymphoma: 5-year analysis of the IELSG-19 Randomized Study. J Clin Oncol. 2013 Feb 10;31(5):565-72. doi: 10.1200/JCO.2011.40.6272. Epub 2013 Jan 7.

    PubMed 23295789

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing chlorambucil (drug), rituximab+chlorambucil and rituximab in people with Lymphoma, Mucosa-Associated Lymphoid Tissue, run by International Extranodal Lymphoma Study Group (IELSG) at 75 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 75 sites in United Kingdom, Italy, France, Belgium, Spain and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Jun 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Event-free-survival (EFS) (time frame: 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00210353, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jun 2019.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in