Combined Rituximab and Lenalidomide Treatment for Untreated Patients With Follicular Lymphoma

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effect of the combined treatment of lenalidomide and rituximab in controlling the Follicular Lymphoma disease and also increase the length of response compared to the available standard combination chemotherapy treatment for Follicular Lymphoma.

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. The 'Relevance' cooperative group trial 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 Follicular Lymphoma patients enrolled in both studies will be analyzed.

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 in Subjects With Previously Untreated Follicular Lymphoma

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 follicular lymphoma grade 1, 2 or 3a, Stage II-IV Have no prior systemic treatment for lymphoma Symptomatic follicular lymphoma requiring treatment. Age ≥18 years Eastern Cooperative oncology group performance status 0-2 Willing to follow pregnancy precautions Exclusion Criteria: Clinical evidence of transformed lymphoma or Grade 3b follicular lymphoma. 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), human immunodeficiency virus (HIV) Known sensitivity or allergy to murine products. Presence or history of central nervous system involvement by lymphoma At high risk for a venous thromboembolic event (VTE) and not willing to take VTE prophylaxis Any of the following laboratory abnormalities: serum aspartate transaminase or alanine transaminase > 3x upper limit of normal (ULN), except in patients with documented liver involvement by lymphoma total bilirubin > 2.0 mg/dl (34 µmol/L) except in cases of Gilberts Syndrome and documented liver or pancreatic involvement by lymphoma creatinine clearance of < 30 mL/min

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 for 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 up to 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>* 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>Drug: Lenalidomide<br>* 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>* 7 to 8 weeks later responding patients will continue with 375 mg/m2 rituximab every 8 weeks for 12 cycles.<br>Drug: Rituximab-CVP<br>* 7 to 8 weeks later responding patients will continue with 375 mg/m2 rituximab every 8 weeks for 12 cycles.<br>Drug: Rituximab-Bendamustine<br>* 7 to 8 weeks later responding patients will 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 (CR/CRu) at 120 weeks | The tumor response data will be assessed by the IRC using the IWG (Cheson, 1999) criteria. Based on the CT/MRI schedule, any assessments in a time window of 120 weeks ± 4 weeks are qualified as the 120 week assessments. | Up to approximately 2.5 years | 
| Progression free survival (PFS)Follicular lymphoma | Is defined as the time from randomization into the study to the first observation of documented disease progression or death due to any cause. | Up to 12 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events |  | Up to 13 years | 
| Time to Treatment Failure (TTF)Follicular Lymphoma | Time to Treatment Failure (TTF)Follicular Lymphoma | Up to 13 years | 
| Number of Participants who Survive without an Event(s) | Event Free Survival (EFS)Follicular Lymphoma | Up to 13 years | 
| Time to Next Anti-Lymphoma Treatment (TTNLT) for Follicular Lymphoma | TTNLT will be measured from the date of randomization to the date of first documented administration of any new anti-lymphoma treatment (chemotherapy, radiotherapy, radio immunotherapy, immunotherapy). Patients continuing in response or who are lost to follow-up will be censored on their last visit date. Patients who died (due to any cause) before having received a new anti-lymphoma | Up to 12 years | 
| Time to Next Chemotherapy Treatment (TTNCT) for Follicular Lymphoma | Time to Next Chemotherapy Treatment (TTNCT) for Follicular Lymphoma | Up to 13 years | 
| Number of participants alive or dead |  | Up to 13 years | 
| Overall response by International Working Group (IWG) 1999 criteria |  | Up to 120 weeks | 
| Health related quality of life as measured by the EORTC QLQ-C30 for Follicular Lymphoma patients | Health related quality of life as measured by the EORTC QLQ-C30 for Follicular Lymphoma patients | Up to 13 years | 
| Event-Free Survival (EFS) | EFS will be measured from the date of randomization to the date of first documented progression, relapse, and initiation of a new anti-lymphoma treatment or death by any cause. Responding patients and patients who are lost to follow up will be censored at their last tumor assessment date. | Up to 12 years | 
| Overall Survival (OS) | Will be measured from date of randomization to the date of death | up to 12 years | 
| Complete Response Rate (CR/CRu) at 120 weeks | The tumor response data will be assessed by the IRC using the IWG (Cheson, 1999) criteria. Based on the CT/MRI schedule, any assessments in a time window of 120 weeks ± 4 weeks are qualified as the 120 week assessments. | Up to approximately 2.5 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