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

NCT ID: NCT00210353

Last Updated: 2019-06-06

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

454 participants

Study Classification

INTERVENTIONAL

Study Start Date

2003-01-31

Study Completion Date

2016-02-17

Brief Summary

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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

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Conditions

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Lymphoma, Mucosa-Associated Lymphoid Tissue

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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)

Group Type ACTIVE_COMPARATOR

chlorambucil (drug)

Intervention Type 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 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

Group Type EXPERIMENTAL

rituximab+chlorambucil

Intervention Type DRUG

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

ARM C (Since April 2006)

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

Group Type EXPERIMENTAL

rituximab

Intervention Type DRUG

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

Interventions

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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)

Intervention Type 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

Intervention Type DRUG

rituximab

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

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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International Extranodal Lymphoma Study Group (IELSG)

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Emanuele Zucca, MD

Role: STUDY_CHAIR

International Extranodal Lymphoma Study Group/Oncology Institute of Southern Switzerland. Bellinzona

Emilio Montserrat, MD

Role: STUDY_CHAIR

Clinic Hospital Universitari, Hematology. Barcelona

Catherine Thieblemont, MD

Role: STUDY_CHAIR

Centre Hospitalier Lyon Sud, Hematology. Lyon

Giovanni Martinelli, MD

Role: STUDY_CHAIR

Hemato-oncology. European Oncology Institute. Milan

Peter Johnson, MD

Role: STUDY_CHAIR

Oncology Unit. Southampton General Hospital. Southampton

Maurizio Martelli, MD

Role: STUDY_CHAIR

Hematology. Università La Sapienza. Roma

Locations

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ACZA Campus Stuivenberg

Antwerp, , Belgium

Site Status

AZ StJan

Bruges, , Belgium

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St Luc

Brussels, , Belgium

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ULB Hopital Erasme

Brussels, , Belgium

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CHNDRF

Charleroi, , Belgium

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Hospital St Joseph

Gilly, , Belgium

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UCL de Mont Godinne

Yvoir, , Belgium

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Centre Hospitalier de Blois

Blois, , France

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Hopital Avicenne

Bobigny, , France

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CHU

Dijon, , France

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Centre Hospitalier

Lens, , France

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CHRU Lille

Lille, , France

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Centre Hospitalier Lyon Sud

Lyon, , France

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Centre Leon Berard

Lyon, , France

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Institut Paoli Calmettes

Marseille, , France

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Hopital Arnold Villeneuve

Monpellier, , France

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CHU

Nancy, , France

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CHU Hotel Dieu

Nantes, , France

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Centre R. Gauducheau

Nantes-St. Herblain, , France

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Hopital Henri-Mondor

Paris, , France

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Hopital St Louis

Paris, , France

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Necker

Paris, , France

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Centre Henri Becquerel

Rouen, , France

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Spedali Civili

Brescia, , Italy

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Azienda ULSS 15 Alta Padovana

Cittadella, , Italy

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IST

Genova, , Italy

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Humanitas

Milan, , Italy

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San Raffaele Hospital

Milan, , Italy

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IEO

Milan, , Italy

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INT

Milan, , Italy

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Policlinico

Modena, , Italy

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Ospedale Civile

Piacenza, , Italy

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

Reggio Calabria, , Italy

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Arcispedale S. Maria Nuova

Reggio Emilia, , Italy

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S. Eugenio

Rome, , Italy

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Università Cattolica Sacro Cuore

Rome, , Italy

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Università La Sapienza

Rome, , Italy

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Sassuolo GISL

Sassuolo, , Italy

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AOU Senese

Siena, , Italy

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

Torino, , Italy

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Trani GISL

Trani, , Italy

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Ospedale di Circolo Fondazione Macchi

Varese, , Italy

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Policlinico GB Rossi

Verona, , Italy

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Clinic Hospital Universitari

Barcelona, , Spain

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Hopital Mataro'

Barcelona, , Spain

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Hopital Santa Creu i Sant Pau

Barcelona, , Spain

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University Hospital

Salamanca, , Spain

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Joan XXIII

Tarragona, , Spain

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IOSI

Bellinzona, , Switzerland

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Aberdeen Royal Infirmary

Aberdeen, , United Kingdom

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Heartlands

Birmingham, , United Kingdom

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Victoria Hospital

Blackpool, , United Kingdom

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Royal Cornwall Hospital

Cornwall, , United Kingdom

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Darent Valley Hospital

Dartford, , United Kingdom

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Royal Devon &Exeter Healtcare NHS Trust

Devon, , United Kingdom

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Russels Hall Hospital

Dudley, , United Kingdom

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Western General Hospital

Edinburgh, , United Kingdom

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Medway Hospital

Gillingham, , United Kingdom

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Raigmore Hospital

Inverness, , United Kingdom

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Liverpool Royal Hospital

Liverpool, , United Kingdom

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University Hospital Aintree

Liverpool, , United Kingdom

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Barts & the London NHS Trust

London, , United Kingdom

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Royal Marsden NHS Foundation Trust

London, , United Kingdom

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St Georges

London, , United Kingdom

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Christie Hospital

Manchester, , United Kingdom

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Mount Vernon Hospital

Middlesex, , United Kingdom

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James Paget Hospital

Norfolk, , United Kingdom

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Queen Elisabeth

Norfolk, , United Kingdom

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Nottingham City Hospital

Nottingham, , United Kingdom

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John Radcliffe

Oxford, , United Kingdom

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Conquest Hospital

Saint Leonard on Sea, , United Kingdom

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Weston Park

Sheffield, , United Kingdom

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Southampton General Hospital

Southampton, , United Kingdom

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Sandwell General Hospital

West Bromwich, , United Kingdom

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Worchestershire Acute Hospital NHS Trust

Worcester, , United Kingdom

Site Status

Countries

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Belgium France Italy Spain Switzerland United Kingdom

References

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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.

Reference Type DERIVED
PMID: 37801707 (View on PubMed)

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.

Reference Type DERIVED
PMID: 23295789 (View on PubMed)

Related Links

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http://www.ielsg.org

Click here for more information about this study

Other Identifiers

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IELSG19

Identifier Type: -

Identifier Source: org_study_id

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