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Rituximab in Treating Patients With Newly Diagnosed Stage II, Stage III, or Stage IV Follicular Non-Hodgkin's 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: NCT00112931
Recruitment Status : Active, not recruiting
First Posted : June 3, 2005
Last Update Posted : May 10, 2023
Cancer Research UK
Roche Pharma AG
Information provided by (Responsible Party):
University College, London

Brief Summary:

RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. It is not yet known whether rituximab is more effective than observation in treating non-Hodgkin's lymphoma.

PURPOSE: This randomized phase III trial is studying rituximab to see how well it works compared to observation in treating patients with newly diagnosed stage II, stage III, or stage IV follicular non-Hodgkin's lymphoma with no symptoms.

Condition or disease Intervention/treatment Phase
Lymphoma Biological: rituximab Other: No treatment Phase 3

Detailed Description:



  • Compare time to initiation of systemic chemotherapy or radiotherapy in patients with newly diagnosed, previously untreated, asymptomatic stage II-IV non-bulky follicular non-Hodgkin's lymphoma treated with rituximab vs observation only.


  • Compare the frequency of clinical spontaneous remission in patients treated with these regimens.
  • Compare overall and cause-specific survival of patients treated with these regimens.
  • Determine the effect of rituximab on complete and partial response in patients treated with subsequent systemic chemotherapy.
  • Compare quality of life, in terms of functional well-being and anxiety and depression, of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, disease grade (1 vs 2 vs 3a), disease stage (II vs III vs IV), and age. Patients are randomized to 1 of 3 treatment arms.

  • Arm I: Patients undergo observation only until disease progression.
  • Arm II: Patients receive induction rituximab IV on day 1. Treatment repeats weekly for up to 4 weeks.
  • Arm III: Patients receive induction rituximab as in arm II. Patients then receive maintenance rituximab IV once on day 1 of weeks 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, and 100.

In all arms, treatment continues in the absence of unacceptable toxicity or disease progression requiring systemic chemotherapy* or radiotherapy.

NOTE: *Rituximab administration in arm I is considered initiation of systemic chemotherapy

Quality of life is assessed at baseline (before and after randomization), every 2 months for 2 years, and then every 6 months for 2 years.

Patients are followed every 2 months for 2 years and then every 3 months thereafter.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 600 patients (200 per treatment arm) will be accrued for this study within 3 years.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 600 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Intergroup Randomised Trial of Rituximab Versus a Watch and Wait Strategy in Patients With Advanced Stage, Asymptomatic, Non-Bulky Follicular Lymphoma
Study Start Date : September 2004
Actual Primary Completion Date : March 2014
Estimated Study Completion Date : May 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma
Drug Information available for: Rituximab

Arm Intervention/treatment
Active Comparator: Watch and Wait
Watch and Wait - no treatment
Other: No treatment
Experimental: Arm C Rituximab 4 and Rixuximab Maintenance
4 infusions - 375mg/m2 every 2 months. A single dose of rituximab (375mg/m2 will then be given at 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92 and 100 weeks
Biological: rituximab

Primary Outcome Measures :
  1. Time until initiation of therapy (chemotherapy or radiotherapy) [ Time Frame: Time from randomisation until the first day systemic chemotherapy or radiotherapy is given. If rituximab is given to patients in the watch and wait arm this will be considered as initiation of chemotherapy. ]

Secondary Outcome Measures :
  1. Frequency of clinical spontaneous remission [ Time Frame: From randomisation until the initiation of chemotherapy in the watch and wait arm ]
  2. Cause specific survival [ Time Frame: Time from randomisation to death from lymphoma or immediate therapy related toxicity ]
  3. Overall survival [ Time Frame: Time from randomisation to death from any cause. ]
  4. Response rate at 25 months [ Time Frame: Response at 25 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically confirmed follicular non-Hodgkin's lymphoma

    • Diagnosed within the past 3 months
    • Grade 1, 2, or 3a disease
    • Stage II-IV disease
    • No evidence of histological transformation
  • Bidimensionally measurable disease by clinical examination or radiography
  • Asymptomatic disease without B symptoms or severe pruritus
  • Low tumor burden, defined by all of the following criteria:

    • Lactic dehydrogenase normal
    • Largest nodal or extranodal mass < 7 cm
    • No more than 3 nodal sites with a diameter > 3 cm
    • No clinically detectable significant serous effusion by chest x-ray

      • Clinically non-evident small effusion on CT scan is not considered significant
    • Spleen enlargement ≤ 16 cm by CT scan
  • Circulating tumor cells < 5,000/mm^3
  • No organ compression (i.e., ureteric obstruction)



  • 18 and over

Performance status

  • ECOG 0-1

Life expectancy

  • Not specified


  • Absolute neutrophil count > 1,500/mm^3
  • Platelet count > 100,000/mm^3
  • Hemoglobin > 10 g/dL


  • AST and ALT normal
  • Alkaline phosphatase normal
  • Bilirubin normal


  • Creatinine < 2 times upper limit of normal (unless due to lymphoma)


  • Not pregnant or nursing
  • Fertile patients must use effective contraception during and for 12 months after completion of rituximab
  • No known HIV positivity
  • No other malignancy within the past 2 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
  • No critical organ failure
  • No other immediate life-threatening disease


Biologic therapy

  • Not specified


  • Not specified

Endocrine therapy

  • Not specified


  • Not specified


  • Not specified


  • No prior therapy for lymphoma

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): NCT00112931

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Sponsors and Collaborators
University College, London
Cancer Research UK
Roche Pharma AG
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Study Chair: Kirit Ardeshna Mount Vernon Cancer Centre at Mount Vernon Hospital
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT00112931    
Other Study ID Numbers: CDR0000427312
First Posted: June 3, 2005    Key Record Dates
Last Update Posted: May 10, 2023
Last Verified: May 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by University College, London:
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
noncontiguous stage II grade 1 follicular lymphoma
noncontiguous stage II grade 2 follicular lymphoma
noncontiguous stage II grade 3 follicular lymphoma
contiguous stage II grade 1 follicular lymphoma
contiguous stage II grade 2 follicular lymphoma
contiguous stage II grade 3 follicular lymphoma
Additional relevant MeSH terms:
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Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents