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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. Identifier: NCT00112931
Recruitment Status : Active, not recruiting
First Posted : June 3, 2005
Last Update Posted : February 15, 2019
Cancer Research UK
Roche Pharma AG
Information provided by (Responsible Party):
University College, London

Tracking Information
First Submitted Date  ICMJE June 2, 2005
First Posted Date  ICMJE June 3, 2005
Last Update Posted Date February 15, 2019
Study Start Date  ICMJE September 2004
Actual Primary Completion Date March 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 14, 2016)
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. ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 14, 2016)
  • Frequency of clinical spontaneous remission [ Time Frame: From randomisation until the initiation of chemotherapy in the watch and wait arm ]
  • Cause specific survival [ Time Frame: Time from randomisation to death from lymphoma or immediate therapy related toxicity ]
  • Overall survival [ Time Frame: Time from randomisation to death from any cause. ]
  • Response rate at 25 months [ Time Frame: Response at 25 months ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Rituximab in Treating Patients With Newly Diagnosed Stage II, Stage III, or Stage IV Follicular Non-Hodgkin's Lymphoma
Official Title  ICMJE An Intergroup Randomised Trial of Rituximab Versus a Watch and Wait Strategy in Patients With Advanced Stage, Asymptomatic, Non-Bulky Follicular Lymphoma
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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Lymphoma
Intervention  ICMJE
  • Biological: rituximab
  • Other: No treatment
Study Arms  ICMJE
  • Active Comparator: Watch and Wait
    Watch and Wait - no treatment
    Intervention: 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
    Intervention: Biological: rituximab
Publications * Ardeshna KM, Qian W, Smith P, Braganca N, Lowry L, Patrick P, Warden J, Stevens L, Pocock CF, Miall F, Cunningham D, Davies J, Jack A, Stephens R, Walewski J, Ferhanoglu B, Bradstock K, Linch DC. Rituximab versus a watch-and-wait approach in patients with advanced-stage, asymptomatic, non-bulky follicular lymphoma: an open-label randomised phase 3 trial. Lancet Oncol. 2014 Apr;15(4):424-35. doi: 10.1016/S1470-2045(14)70027-0. Epub 2014 Mar 4.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: November 8, 2006)
Original Enrollment  ICMJE Not Provided
Estimated Study Completion Date  ICMJE May 2022
Actual Primary Completion Date March 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE


  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 120 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   New Zealand,   United Kingdom
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT00112931
Other Study ID Numbers  ICMJE CDR0000427312
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party University College, London
Study Sponsor  ICMJE University College, London
Collaborators  ICMJE
  • Cancer Research UK
  • Roche Pharma AG
Investigators  ICMJE
Study Chair: Kirit Ardeshna Mount Vernon Cancer Centre at Mount Vernon Hospital
PRS Account University College, London
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP