A Phase 3 Open Label Randomized Study to Compare the Efficacy and Safety of Rituximab Plus Lenalidomide (CC-5013) Versus Rituximab Plus Chemotherapy Followed by Rituximab in Subjects With Previously Untreated Follicular Lymphoma

Study Overview
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Brief Summary
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The purpose of this study is to find out if lenalidomide when given along with rituximab can help to control the disease and also increase the length of your response (complete or partial response) compared to the standard of care rituximab chemotherapy treatment.

Detailed Description
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Follicular Lymphoma (FL) is a cancer of a B lymphocyte, a type of white blood cell. FL is typically a slowly progressing but incurable disease. Follicular lymphoma cells produce a specific defect in the patient's immune system impairing their ability to control their cancer. Lenalidomide has been shown to reverse the specific immune defect caused by FL in the patient. By including lenalidomide, the RELEVANCE study aims to eliminate the cancer while restoring the patient's immune competence.

Official Title
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A PHASE 3 OPEN-LABEL RANDOMIZED STUDY TO COMPARE THE EFFICACY AND SAFETY OF RITUXIMAB PLUS LENALIDOMIDE (CC-5013) VERSUS RITUXIMAB PLUS CHEMOTHERAPY FOLLOWED BY RITUXIMAB IN SUBJECTS WITH PREVIOUSLY UNTREATED FOLLICULAR LYMPHOMA The RELEVANCE Trial (Rituximab Lenalidomide Versus ANy ChEmotherapy)is Being Conducted as Two Companion Studies: RV-FOL-GELARC-0683 (N=750) and RV-FOL-GELARC-0683C (N=250); the Combined Total of 1000 Patients Enrolled in Both Studies Will be Analyzed.

Conditions
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Follicular Lymphoma

Intervention / Treatment
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* Drug: Rituximab
* Drug: Lenalidomide
* Drug: Rituximab - CHOP
* Drug: Rituximab - CVP
* Drug: Rituximab - Bendamustine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed CD20+ follicular lymphoma grade 1, 2 or 3a Have no prior systemic treatment for lymphoma. Must be in need of treatment Bi-dimensionally measurable disease with at least one mass lesion > 2 cm that was not previously irradiated. Stage II, III or IV disease. Must be ≥ 18 years and sign an informed consent. Performance status ≤ 2 on the ECOG scale. Adequate hematological function (unless abnormalities are related to lymphoma infiltration of the bone marrow) Willing to follow pregnancy precautions Exclusion Criteria: Clinical evidence of transformed lymphoma by investigator assessment or Grade 3b follicular lymphoma. Patients taking corticosteroids during the last 4 weeks, unless administered at a dose equivalent to < 10 mg/day prednisone (over these 4 weeks). Major surgery (excluding lymph node biopsy) within 28 days prior to signing informed consent. Known Seropositive for or active viral infection with hepatitis B virus (HBV), hepatitis C virus (HCV)or human immunodeficiency virus (HIV). Life expectancy < 6 months. Known sensitivity or allergy to murine products. Prior history of malignancies, other than follicular lymphoma, unless the patient has been free of the disease for ≥ 10 years. Prior use of lenalidomide. Neuropathy > Grade 1. Presence or history of CNS involvement by lymphoma. Patients who are at a high risk for a thromboembolic event and are not willing to take venous thromboembolic (VTE) prophylaxis. serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) > 3x upper limit of normal (ULN), except in patients with documented liver or pancreatic involvement by lymphoma total bilirubin > 2.0 mg/dl (34 µmol/L) except in cases of Gilberts Syndrome and documented liver involvement by lymphoma creatinine clearance of < 30 mL/min Pregnant or lactating females. Any condition, including the presence of laboratory abnormalities, which places the patient at unacceptable risk if he/she were to participate in the study, or which confounds the ability to interpret data from the study.

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 |
| --- | --- |
| Experimental: Lenalidomide + Rituximab<br>Lenalidomide dose 20-mg on days 2-22 every 28 days x 6 cycles, if CR then 10-mg on days 2-22 every 28 days for 12 cycles. PR after 6 cycles, continue 20 mg for 3 6 cycles and then 10 mg on days 2-22 every 28-day cycles for upto 18 cycles Rituximab, 375 mg/m2 on days 1, 8, 15 and 22 of cycle 1, day 1 of cycles 2 to 6; 8 weeks later responding patients continue with 375 mg/m2 rituximab every 8 weeks for 12 cycles. | Drug: Rituximab<br>* • Rituximab, 375 mg/m2 on days 1, 8, 15 and 22 of cycle 1, day 1 of cycles 2 to 6; 8 weeks later responding patients continue with 375 mg/m2 rituximab every 8 weeks for 12 cycles.<br>* Other names: rituxan;Drug: Lenalidomide<br>* • Lenalidomide dose 20-mg on days 2-22 every 28 days x 6 cycles, if CR then 10-mg on days 2-22 every 28 days for 12 cycles. PR after 6 cycles, continue 20 mg for 3 6 cycles and then 10 mg on days 2-22 every 28-day cycles for upto 18 cycles<br>* Other names: Revlimid;|
| Active Comparator: Control<br>• ONE of the following: Rituximab - CHOP, Rituximab - CVP, Rituximab - Bendamustine. 7 to 8 weeks later responding patients will continue with 375 mg/m2 rituximab every 8 weeks for 12 cycles. | Drug: Rituximab - CHOP<br>* six cycles of R-CHOP in 21 day cycles followed by two 21 day cycles of 375 mg/m2 rituximab; and 7 weeks later responding patients continue with 375 mg/m2 rituximab every 8 weeks for 12 cycles<br>Drug: Rituximab - CVP<br>* eight cycles of R-CVP in 21 day cycles; and 7 weeks later responding patients continue with 375 mg/m2 rituximab every 8 weeks for 12 cycles,<br>Drug: Rituximab - Bendamustine<br>* six cycles of R-B in 28 day cycles and 8 weeks later responding patients continue with 375 mg/m2 rituximab every 8 weeks for 12 cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| COMPLETE RESPONSE RATE | Complete response (CR/CRu) rate at 120 weeks Response evaluation was as defined by International Working Group (IWG) Response Criteria (Cheson 1999). Complete response (CR) is defined as the complete disappearance of all detectable clinical and radiographic evidence of disease and the disappearance of all disease-related symptoms if present before therapy. | Timeframe: CR/CRu rate at 120 weeks | 
| Progression Free Survival (PFS) | PFS is defined as the time from the start of study drug therapy to the 1st observation of disease progression or death due to any cause. | up to 13 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events |  | up to13 years | 
| Time to Treatment Failure (TTF) |  | up to13 years | 
| Event Free Survival (EFS) |  | up to13 years | 
| Time to Next Anti-Lymphoma Treatment (TTNLT), |  | up to13 years | 
| Time to Next Chemotherapy Treatment (TTNCT) |  | up to13 years | 
| Overall Survival (OS) |  | up to13 years | 
| Overall response rate at 120 weeks by International Working Group (IWG) 1999 criteria |  | up to13 years | 
| Health related quality of life as measured by the EORTC QLQ-C30 |  | up to13 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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follicular lymphoma, non-hodgkins follicular lymphoma, treatment for follicular lymphoma, rituximab treatment, rituximab and lenalidomide treatment