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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00210353
Recruitment Status : Active, not recruiting
First Posted : September 21, 2005
Last Update Posted : July 27, 2016
Information provided by (Responsible Party):

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

Condition or disease Intervention/treatment Phase
Lymphoma, Mucosa-Associated Lymphoid Tissue Drug: chlorambucil (drug) Drug: rituximab+chlorambucil Drug: rituximab Phase 3

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 450 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : January 2003
Estimated Primary Completion Date : April 2017
Estimated Study Completion Date : April 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :
  1. Event-free-survival (EFS) (failure or death from any cause) for all patients [ Time Frame: 5 years ]

Secondary Outcome Measures :
  1. Complete and partial remission rates for all patients [ Time Frame: end of treatment ]
  2. Response duration (time to relapse or progression) for responder patients [ Time Frame: 5 years ]
  3. Progression-free-survival (PFS) (disease progression or death from lymphoma: for all patients [ Time Frame: 5 years ]
  4. Overall survival for all patients [ Time Frame: 5 years ]
  5. Acute and long-term toxicity [ Time Frame: 5 years ]

Eligibility Criteria

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00210353

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

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: International Extranodal Lymphoma Study Group (IELSG)
ClinicalTrials.gov Identifier: NCT00210353     History of Changes
Other Study ID Numbers: IELSG19
First Posted: September 21, 2005    Key Record Dates
Last Update Posted: July 27, 2016
Last Verified: July 2016

Additional relevant MeSH terms:
Lymphoma, B-Cell, Marginal Zone
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action