RATIONALE: Lenalidomide may stimulate the immune system in different ways and stop cancer cells from growing. 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. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, vincristine, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving lenalidomide together with rituximab and combination chemotherapy may kill more cancer cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of lenalidomide when given together with rituximab and combination chemotherapy and to see how well they work in treating patients with newly diagnosed stage II, stage III, or stage IV diffuse large cell or follicular B-cell lymphoma.
OBJECTIVES: Primary * To determine the maximum tolerated dose of lenalidomide when given in combination with rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone in patients with newly diagnosed stage II-IV diffuse large cell or grade 3 follicular B-cell lymphoma. (Phase I) * To assess the efficacy of this regimen, in terms of event-free survival and response rate, in these patients. (Phase II) * To assess the safety of this regimen in these patients. (Phase II) Secondary * To assess the host immune function at baseline and after treatment and correlate these parameters with tumor response and event-free survival. OUTLINE: This is a multicenter, phase I dose-escalation study of lenalidomide followed by a phase II study. * Phase I: Patients receive rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine IV on day 1, oral prednisone on days 1-5, and oral lenalidomide on days 1-10. Patients also receive pegfilgrastim subcutaneously on day 2. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. * Phase II: Patients receive lenalidomide at the maximum tolerated dose determined in phase I and rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, prednisone, and pegfilgrastim as in phase I. Blood is collected at baseline, before course 3, and after completion of study treatment for translational research studies. Research studies include immune function and cytokine analysis, T- and B- quantitative lymphocyte analysis, and single nucleotide polymorphism analysis. After completion of study therapy, patients are followed every 3 months for 1 year, every 4 months for 1 year, and then every 6 months for 3 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
138
Mayo Clinic in Arizona
Scottsdale, Arizona, United States
Mayo Clinic in Florida
Jacksonville, Florida, United States
Mayo Clinic
Rochester, Minnesota, United States
Toxicity as Assessed by NCI CTCAE v3.0 (Phase I)
Time frame: 5 years
Event-free > Survival at 12 Months (Phase 2, DLBCL/Mixed Dose Level 3)
Other Phase II Cohorts were not evaluable for event-free survival analysis.
Time frame: 1 year
Progression-free > Survival at 24 Months (Phase 2, Transformed/Composite)
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions Other Phase II Cohorts were not evaluable for progression-free survival analysis.
Time frame: 2 years
Overall Response Rate
Time frame: When all patients either have a CR or have completed observation.
Overall Complete Response Rate
Time frame: When all patients either have a CR or have completed observation.
Event-free Survival
Time frame: 5 years
Overall Survival
Time frame: 5 years
Progression-free Survival
Time frame: 5 years
Duration of Response
Time frame: 5 years
Immune Function Before and After Treatment as Assessed by T-, B-, and NK-cell Quantification
Time frame: 5 years
Correlation of Immune Function With Clinical Outcomes
Time frame: 5 years
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