Rituximab in Treating Patients With Newly Diagnosed Stage II, Stage III, or Stage IV Follicular Non-Hodgkin's Lymphoma

University College London (UCL)

Status and phase: Completed; Phase 3

Conditions: Lymphoma

Treatments: Other: No treatment; Biological: rituximab

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00112931

CRUK-2004-001621-16

EU-20509

CDR0000427312

ROCHE-CRUK-001621-16

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 462 patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• 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)

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

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

Hepatic

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

Renal

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

Other

• 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

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• No prior therapy for lymphoma

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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462 participants in 2 patient groups

Watch and Wait

Active Comparator group

Description:

Watch and Wait - no treatment

Treatment:

Other: No treatment

Arm C Rituximab 4 and Rixuximab Maintenance

Experimental group

Description:

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

Treatment:

Biological: rituximab