• Time until initiation of therapy (chemotherapy or radiotherapy) [ Designated as safety issue: No ]
  

• Frequency of clinical spontaneous remission [ Designated as safety issue: No ]
  
• Cause specific survival [ Designated as safety issue: No ]
  
• Overall survival [ Designated as safety issue: No ]
  
• Disease-free survival [ Designated as safety issue: No ]
  
• Response rate [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• 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.

Secondary

• 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.