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

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ClinicalTrials.gov Identifier: NCT00210353
Recruitment Status : Completed
First Posted : September 21, 2005
Results First Posted : June 6, 2019
Last Update Posted : June 6, 2019
Sponsor:
Information provided by (Responsible Party):
International Extranodal Lymphoma Study Group (IELSG)

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 454 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
Actual Primary Completion Date : April 2015
Actual Study Completion Date : February 17, 2016


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




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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.


  2. 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).


  3. Progression-free-survival (PFS) [ Time Frame: 5 years ]
    Percentage of patients without disease progression after 5 years from trial registration

  4. Overall Survival [ Time Frame: 5 years ]
    Percentage of patients alive after 5 years from trial registration



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

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

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


  Show 75 Study Locations
Sponsors and Collaborators
International Extranodal Lymphoma Study Group (IELSG)
Investigators
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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

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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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
Results First Posted: June 6, 2019
Last Update Posted: June 6, 2019
Last Verified: October 2018

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