RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer cell 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. Lenalidomide may stop the growth of non-Hodgkin lymphoma by blocking blood flow to the cancer. It is not yet known whether rituximab is more effective when given alone or together with lenalidomide in treating patients with follicular lymphoma. PURPOSE: This randomized phase II trial is studying rituximab to see how well it works compared with giving rituximab together with lenalidomide in treating patients with previously untreated follicular lymphoma.
OBJECTIVES: Primary * To determine the activity of rituximab in combination with lenalidomide versus rituximab alone in patients with previously untreated follicular lymphoma in need of therapy. Secondary * To determine the safety of these regimens in these patients. OUTLINE: This is a multicenter study. Patients are stratified according to grade of disease (grades 1 or 2 vs 3a), presence of bulky disease (defined as masses ≥ 6 cm) (yes vs no), Follicular Lymphoma International Prognostic Index score (1 or 2 vs ≥ 3), and participating centers. Patients are randomized to 1 of 2 treatment arms. * Arm A: Patients receive rituximab IV on day 1 in weeks 1, 2, 3, 4 and weeks 12, 13, 14, 15 in the absence of disease progression or unacceptable toxicity. * Arm B: Patients receive rituximab IV as in arm A. Patients also receive oral lenalidomide once daily, starting 14 days before first rituximab administration and last until 14 days after the last rituximab administration, in the absence of disease progression or unacceptable toxicity. All patients undergo restaging at week 10. Patients who show less than a minimal response (i.e., reduction of more than 25% in sum of product of diameters \[SPD\]) are off study treatment and transferred to the follow-up phase. Patients undergo a second restaging in week 23. Some patients may undergo biopsies and blood and bone marrow sample collection periodically for biomarker studies. After completion of study treatment, patients are followed up periodically for 20 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
154
Rituximab (MabThera®) will be administered for a maximum of 8 infusions at weeks 1, 2, 3, 4 and again at weeks 12, 13, 14, 15 if the first restaging at week 10 (+/- 1 week) shows a partial response with at least more than 25% reduction in sum of product of diameters
Lenalidomide will be administered as 15 mg flat dose daily, starting 14 days before first and stopping 14 days after last rituximab administration.
Haukeland Hospital - University of Bergen
Bergen, Norway
Sorlandet Sykehus HF Kristiansand
Kristiansand, Norway
Ullevaal University Hospital
Oslo, Norway
Helse Stavanger HF
Stavanger, Norway
University Hospital of North Norway - Tromso
Tromsø, Norway
St. Olavs University Hospital
Complete response (CR)
The evaluation of CR is outlined in Appendix 1 Criteria for Evaluation of Response in Non-Hodgkin's Lymphoma.
Time frame: at week 23
Best overall response (OR)
OR is defined as either: * the disappearance of all evidence of disease (CR or CRu) * the regression of measurable disease with no new sites (PR)
Time frame: within 24 weeks
Best Overall response (OR)
OR is defined as either: * the disappearance of all evidence of disease (CR or CRu) * the regression of measurable disease with no new sites (PR)
Time frame: within 12 weeks
Progression-free survival
PFS will be calculated from randomization until the first event of interest: * disease progression or relapse according to criteria of Cheson et a.l 1999 * death from any cause
Time frame: until disease progression, for up to 10 years after randomization
Time to first off-trial anti-lymphoma therapy
This will be calculated from randomization until the start of the first off-trial anti-lymphoma treatment. Patients not receiving any off-trial anti-lymphoma treatment will be censored at the last follow-up visit.
Time frame: until off-trial therapy administration, for up to 10 years after randomization
Overall survival
OS will be calculated from randomization until death. Patients not experiencing an event will be censored at the last date they were known to be alive.
Time frame: every 6 months for up to 10 years after randomization
Adverse events, including laboratory abnormality assessments and vital signs
This will be evaluated using the NCI CTCAE v4.0
Time frame: from inclusion until 30 days after treatment discontinuation
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Trondheim, Norway
Sahlgrenska University Hospital
Gothenburg, Sweden
University Hospital of Linkoping
Linköping, Sweden
Sunderbyn Hospital
Luleå, Sweden
Lund University Hospital
Lund, Sweden
...and 23 more locations