Combined Rituximab and Lenalidomide Treatment for Untreated Patients With Follicular Lymphoma
- Conditions
- Follicular Lymphoma
- Interventions
- Drug: Rituximab-CHOPDrug: Rituximab-CVPDrug: Rituximab-Bendamustine
- Registration Number
- NCT01476787
- Lead Sponsor
- Celgene
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1030
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Control Rituximab-CHOP • 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. Control Rituximab-CVP • 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. Control Rituximab-Bendamustine • 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. Lenalidomide + Rituximab 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. Lenalidomide + Rituximab Lenalidomide * 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.
- Primary Outcome Measures
Name Time Method Complete Response Rate (CR/CRu) at 120 Weeks by Independent Central Review 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) 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 Outcome Measures
Name Time Method 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). Time to Next Lymphoma Treatment (TTNLT) was measured from the date of randomization to the date of the first documented administration of any new anti-lymphoma treatment (such as chemotherapy, radiotherapy, radio-immunotherapy, or immunotherapy). Participants who continued to respond to treatment or who were lost to follow-up were considered censored on their last visit date. Participants who died (due to any cause) before receiving a new anti-lymphoma treatment were included in the statistical analysis, with death being counted as an event. Based on Kaplan-Meier estimates.
Complete Response Rate (CR) at 120 Weeks Per Independent Central Review At 120 weeks The Complete Response Rate (CR) is the percentage of participants who achieve confirmed complete response (CR) at 120 weeks as assessed per Independent Central Review.
- Complete Response (CR): Disappearance of all evidence of disease.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). Event Free Survival (EFS) is defined as the time a participant remains free from certain negative events (disease progression, relapse, initiation of a new anti-lymphoma treatment, or death) between 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 participants and those lost to follow up were censored at their last tumor assessment date.
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.Overall Survival (OS) From randomization to the date of death by any cause (up to approximately 144 months). Overall survival (OS) is defined as the median length of time a participant stays alive from randomization. Participants who died, regardless of the cause of death, were considered to have had an event. Participants who withdrew consent for the study were considered censored at the time of withdrawal. Participants who completed the study and were still alive at the time of the clinical data cut-off date were censored. All participants who were lost to follow-up prior to the clinical data cut-off date were also considered censored at the time of last contact. Based on Kaplan-Meier estimates.
Trial Locations
- Locations (36)
Local Institution - 54103
🇺🇸Chandler, Arizona, United States
Local Institution - 51803
🇺🇸Fullerton, California, United States
Local Institution - 52003
🇺🇸Los Angeles, California, United States
Local Institution - 51603
🇺🇸Colorado Springs, Colorado, United States
Local Institution - 52503
🇺🇸Englewood, Florida, United States
Local Institution - 51703
🇺🇸Orlando, Florida, United States
Local Institution - 53803
🇺🇸Saint Petersburg, Florida, United States
Local Institution - 50803
🇺🇸Chicago, Illinois, United States
Local Institution - 52203
🇺🇸Lexington, Kentucky, United States
Local Institution - 53603
🇺🇸Westminster, Maryland, United States
Local Institution - 50403
🇺🇸Boston, Massachusetts, United States
Local Institution - 50503
🇺🇸Boston, Massachusetts, United States
Local Institution - 53003
🇺🇸Southfield, Michigan, United States
Local Institution - 51003
🇺🇸Saint Louis, Missouri, United States
Local Institution - 54403
🇺🇸Cherry Hill, New Jersey, United States
Local Institution - 53703
🇺🇸Hackensack, New Jersey, United States
Local Institution - 50903
🇺🇸Morristown, New Jersey, United States
Local Institution - 54303
🇺🇸Sparta, New Jersey, United States
Local Institution - 52403
🇺🇸New York, New York, United States
Local Institution - 50203
🇺🇸New York, New York, United States
Local Institution - 51303
🇺🇸Nashville, Tennessee, United States
Local Institution - 51203
🇺🇸Dallas, Texas, United States
Local Institution - 51103
🇺🇸Houston, Texas, United States
Local Institution - 54003
🇺🇸Lubbock, Texas, United States
Local Institution - 53303
🇺🇸Richmond, Virginia, United States
Local Institution - 40722
🇯🇵Chuo-ku, Tokyo, Japan
Local Institution - 52703
🇺🇸Seattle, Washington, United States
Local Institution - 41122
🇯🇵Minato-ku, Tokyo, Japan
Local Institution - 40922
🇯🇵Fukuoka, Japan
Local Institution - 40422
🇯🇵Hiroshima, Japan
Local Institution - 40122
🇯🇵Isehara City, Kanagawa, Japan
Local Institution - 40322
🇯🇵Kobe-city, Japan
Local Institution - 40222
🇯🇵Koto-ku, Tokyo, Japan
Local Institution - 40622
🇯🇵Kyoto-city, Japan
Local Institution - 41022
🇯🇵Sendai-city, Japan
Local Institution - 40522
🇯🇵Shizuoka, Japan