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
- Conditions
- Follicular Lymphoma
- Interventions
- Registration Number
- NCT01650701
- Lead Sponsor
- The Lymphoma Academic Research Organisation
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1030
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 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 - 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 - 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 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. Lenalidomide + Rituximab Lenalidomide * 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.
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS) up to 13 years 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.
COMPLETE RESPONSE RATE Timeframe: CR/CRu rate at 120 weeks 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.
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) up to13 years Time to Next Chemotherapy Treatment (TTNCT) up to13 years Overall response rate at 120 weeks by International Working Group (IWG) 1999 criteria up to13 years 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 Health related quality of life as measured by the EORTC QLQ-C30 up to13 years
Trial Locations
- Locations (35)
Hospital Universitario Vall d´Hebron
🇪🇸Barcelona, Spain
Hospital Clínico Universitario de Valencia
🇪🇸Valencia, Spain
Hospital Ramon y Cajal
🇪🇸Madrid, Spain
Institut Català d'Oncologia de Girona (ICO Girona)
🇪🇸Girona, Spain
CHU Mont-Godinne
🇧🇪Yvoir, Belgium
Concord Repatriation General Hospital
🇦🇺Concord, New South Wales, Australia
Nepean Hospital
🇦🇺Penrith, New South Wales, Australia
Fraser Valley Cancer Centre
🇨🇦Surrey, British Columbia, Canada
Hospital Costa del Sol
🇪🇸Marbella, Spain
CHU Claude Huriez
🇫🇷Lille, France
Tom Baker Cancer Centre
🇨🇦Calgary, Alberta, Canada
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
McGill University Department of Oncology
🇨🇦Montreal, Quebec, Canada
Hospital Clínico de Barcelona
🇪🇸Barcelona, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital Universitario Salamanca
🇪🇸Salamanca, Spain
Wollongong Hospital
🇦🇺Wollongong, New South Wales, Australia
Atlantic Health Sciences Corp - Saint John Regional Hospital
🇨🇦Halifax, Nova Scotia, Canada
UHN-Princess Margaret Hospital
🇨🇦Toronto, Ontario, Canada
Hôpital de l'Enfant-Jesus, CHU de Quebec
🇨🇦Quebec city, Quebec, Canada
Sunnybrook Health Sciences Centre
🇨🇦Toronto, Ontario, Canada
Saskatoon Cancer Centre
🇨🇦Saskatoon, Saskatchewan, Canada
Medizinische Klinik der Universität Tübingen
🇩🇪Tübingen, Baden Wurtemberg, Germany
Uniklinik Köln
🇩🇪Köln, Nordrhein, Germany
LMU Munchën - Klinikum Grosshadern
🇩🇪Munchen, Germany
Policlinico Sant'Orsola-Malpighi
🇮🇹Bologna, Italy
Sant'Andrea Hospital
🇮🇹Roma, Lazio, Italy
Instituto Português Oncologia
🇵🇹Lisboa, Portugal
Hospital Virgen del Rocio
🇪🇸Sevilla, Andaloucia, Spain
Hospital Universitario Mutua de Terrassa
🇪🇸Terrassa, Barcelona, Spain
Hospital Universitario de Canarias
🇪🇸Santa Cruz de Tenerife, Canarias, Spain
Hospital Son Llatzer
🇪🇸Palma, Mallorca, Spain
CHUM Hopital Notre-Dame
🇨🇦Montreal, Quebec, Canada
Moncton Hospital
🇨🇦Moncton, New Brunswick, Canada
BCCA - Vancouver Cancer Centre
🇨🇦Vancouver, British Columbia, Canada