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

Study Overview
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Brief Summary
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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
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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.

Official Title
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An Intergroup Randomised Trial of Rituximab Versus a Watch and Wait Strategy in Patients With Advanced Stage, Asymptomatic, Non-Bulky Follicular Lymphoma

Conditions
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Lymphoma

Intervention / Treatment
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* Biological: rituximab
* Other: No treatment


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Watch and Wait<br>Watch and Wait - no treatment | Other: No treatment<br> <br> |
| Experimental: Arm C Rituximab 4 and Rixuximab Maintenance<br>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<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time until initiation of therapy (chemotherapy or radiotherapy) |  | 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of clinical spontaneous remission |  | From randomisation until the initiation of chemotherapy in the watch and wait arm | 
| Cause specific survival |  | Time from randomisation to death from lymphoma or immediate therapy related toxicity | 
| Overall survival |  | Time from randomisation to death from any cause. | 
| Response rate at 25 months |  | Response at 25 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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