Rituximab and/or Lenalidomide in Treating Patients With Follicular Non-Hodgkin's Lymphoma That is Not Refractory to Rituximab

Study Overview
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Brief Summary
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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. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Lenalidomide may also stop the growth of non-Hodgkin's lymphoma by blocking blood flow to the cancer. Giving rituximab together with lenalidomide may kill more cancer cells. This randomized phase II trial is studying how well rituximab and/or lenalidomide work in treating patients with follicular non-Hodgkin's lymphoma that is not refractory to rituximab.

Detailed Description
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Outline: This is a randomized, multicenter study. Patients are randomized to 1 of 3 treatment arms. Please see the Arms section for a description of each treatment arm. The primary and secondary objectives of the study are provided below. Primary Objectives: To determine the response rate (overall and complete) after lenalidomide therapy and rituximab + lenalidomide in follicular NHL patients who have relapsed. To determine time to progression after lenalidomide therapy and rituximab and lenalidomide in follicular NHL patients who have relapsed. Secondary Objectives: To compare the time to progression of the previous rituximab regimen to that obtained subsequently to lenalidomide therapy and rituximab + lenalidomide. To determine the toxicity profile of lenalidomide therapy and of rituximab and lenalidomide in follicular NHL patients who have received a previous rituximab regimen. To correlate Fc receptor polymorphism profiling with response to lenalidomide or rituximab + lenalidomide in previously treated patients with follicular NHL who have relapsed. To evaluate changes in Natural Killer (NK) cells, activated NK cells, activated T-cells and several plasma cytokines followed by rituximab therapy and correlation of observed changes to objective response rates. After completion of study treatment, patients are followed for up to 10 years from study entry.

Official Title
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A Randomized Phase II Trial of Rituximab Versus Lenalidomide (REVLIMID™, Cc-5013) (IND#73034) Versus Rituximab + Lenalidomide in Recurrent Follicular Non-Hodgkin Lymphoma (NHL) That is Not Rituximab-Refractory

Conditions
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Lymphoma

Intervention / Treatment
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* Biological: rituximab
* Drug: lenalidomide


Participation Criteria
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Eligibility Criteria
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Documentation of Disease Previously treated, histologically confirmed follicle center cell lymphoma, World Health Organization (WHO) classification, grade 1, 2, or 3a Institutional flow cytometry or immunohistochemistry must confirm Cluster of Differentiation 20 (CD20) antigen expression. Prior Treatment Patient must have been treated with rituximab either alone or in combination with chemotherapy. Patient must have a time to progression of ≥ 6 months from last rituximab dose. No corticosteroids within two weeks prior to study, except for maintenance therapy for a non-malignant disease. Maintenance therapy dose may not exceed 20 mg/day prednisone or equivalent. No prior radioimmunotherapy within 12 months of study entry. Age ≥ 18 years. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2. Measurable disease must be present either on physical examination or imaging studies. Non-measurable disease alone is not acceptable. Any tumor mass >1 cm is acceptable.Lesions that are considered non-measurable include the following: Bone lesions Ascites Pleural/pericardial effusion Lymphangitis cutis/pulmonis Bone marrow No known Central Nervous System (CNS) involvement by lymphoma. No known Human Immunodeficiency Virus (HIV) infection. Non-pregnant and non-nursing. Patients with a currently active second malignancy, other than non-melanoma skin cancers, are not eligible. Patients with a recent history (within 3 months of study entry) of Deep Vein Thrombosis/Pulmonary Embolism (DVT/PE) are not eligible. Required Initial Laboratory Values: Absolute Neutrophil Count (ANC) ≥ 1000/µL Platelet count ≥ 75,000/µL Creatinine < 1.5 x Upper Limit of Normal (ULN) unless attributed to lymphoma or calculated clearance > 50 mL/min (patients on dialysis are not eligible) Total Bilirubin ≤ 2 x ULN unless attributed to lymphoma or Gilbert's disease

Ages Eligible for Study
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Minimum Age: 18 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: Arm I - rituximab<br>Patients receive rituximab IV on days 1, 8, 15, and 22. | Biological: rituximab<br>* Given IV<br>|
| Experimental: Arm II - lenalidomide<br>Patients receive oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. | Drug: lenalidomide<br>* Given orally<br>|
| Experimental: Arm III - lenalidomide and rituximab<br>Patients receive lenalidomide as in arm II. Patients also receive rituximab IV on days 8, 15, 22 and 29. | Biological: rituximab<br>* Given IV<br>Drug: lenalidomide<br>* Given orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | Response is assessed by investigator according to International Working Group (IWG) criteria. A complete response requires disappearance of all evidence of disease. A partial response is a >/= 50% decrease in the sum of products of 6 largest dominant nodes or nodal masses as well as for splenic and hepatic nodules. No increase in size of nodes, liver or spleen and no new sites of disease. | Duration of treatment (12 cycles) | 
| Time to Progression | Time to progression (TTP) is defined as the time from study entry until progression or death without progression. The median TTP with 95% CI was estimated using the Kaplan-Meier method. | Up to 10 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma