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
Overview
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Celgene
- Enrollment
- 1,030
- Locations
- 36
- Primary Endpoint
- Complete Response Rate (CR/CRu) at 120 Weeks by Independent Central Review
Overview
Brief Summary
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
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Control
• 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.
Intervention: Rituximab-CHOP (Drug)
Lenalidomide + Rituximab
- 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.
Intervention: Rituximab (Drug)
Lenalidomide + Rituximab
- 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.
Intervention: Lenalidomide (Drug)
Control
• 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.
Intervention: Rituximab-CVP (Drug)
Control
• 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.
Intervention: Rituximab-Bendamustine (Drug)
Outcomes
Primary Outcomes
Complete Response Rate (CR/CRu) at 120 Weeks by Independent Central Review
Time Frame: At 120 weeks
The Complete Response Rate (CR/CRu) is the percentage of participants who achieve complete response (CR/CRu) at 120 weeks as assessed per Independent Central Review. * Complete Response (CR): Disappearance of all evidence of disease. * Complete Response Unconfirmed (CRu): Disappearance of all disease with the exception of residual lymph nodes that are 1.5 cm or less in greatest transverse diameter and/or indeterminate bone marrow findings.
Progression-free Survival (PFS)
Time Frame: From randomization into the study to the first observation of documented disease progression or death due to any cause (up to approximately 140 months).
Progression-free survival (PFS) is defined as the time from randomization into the study to the first observation of documented disease progression or death due to any cause. Progressive Disease (PD) is characterized by any of the following: * An increase of at least 50% in the sum of the products of the greatest diameters (SPD) of any previously identified abnormal lymph node(s) or other disease sites. * The appearance of any new lesion during or after treatment. * An increase of at least 50% in the longest diameter of a previously identified node that was 1 cm or more in its short axis. * An increase of at least 50% in the size of other lesions (e.g., splenomegaly, hepatomegaly). Based on Kaplan-Meier estimates.
Secondary Outcomes
- Time to Next Anti-Lymphoma Treatment (TTNLT)(From the date of randomization to the date of the first documented administration of any new anti-lymphoma treatment (up to approximately 140 months).)
- Complete Response Rate (CR) at 120 Weeks Per Independent Central Review(At 120 weeks)
- Event-free Survival (EFS)(From randomization to the date of first documented progression, relapse, and initiation of a new anti-lymphoma treatment or death by any cause (up to approximately 140 months).)
- Overall Survival (OS)(From randomization to the date of death by any cause (up to approximately 144 months).)