Clinical trial NCT01650701: 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
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Follicular Lymphoma
Keywords: follicular lymphoma
non-hodgkins follicular lymphoma
treatment for follicular lymphoma
rituximab treatment
rituximab and lenalidomide treatment
Lead sponsor: The Lymphoma Academic Research Organisation
Sponsor class: OTHER
Collaborators: name: Celgene Corporation
First posted: 2012-07-26
Enrollment: 1030
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: COMPLETE RESPONSE RATE
timeFrame: Timeframe: CR/CRu rate at 120 weeks
measure: Progression Free Survival (PFS)
timeFrame: up to 13 years
Secondary outcomes:
measure: Number of participants with adverse events
timeFrame: up to13 years
measure: Time to Treatment Failure (TTF)
timeFrame: up to13 years
measure: Event Free Survival (EFS)
timeFrame: up to13 years
measure: Time to Next Anti-Lymphoma Treatment (TTNLT),
timeFrame: up to13 years
measure: Time to Next Chemotherapy Treatment (TTNCT)
timeFrame: up to13 years
measure: Overall Survival (OS)
timeFrame: up to13 years
measure: Overall response rate at 120 weeks by International Working Group (IWG) 1999 criteria
timeFrame: up to13 years
measure: Health related quality of life as measured by the EORTC QLQ-C30
timeFrame: up to13 years
Other outcomes:
Locations:
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
state: New South Wales
city: Penrith
country: Australia
facility: Nepean Hospital
state: New South Wales
city: Wollongong
country: Australia
facility: Wollongong Hospital
state: New South Wales
city: Yvoir
country: Belgium
facility: CHU Mont-Godinne
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Surrey
country: Canada
facility: Fraser Valley Cancer Centre
state: British Columbia
city: Vancouver
country: Canada
facility: BCCA - Vancouver Cancer Centre
state: British Columbia
city: Moncton
country: Canada
facility: Moncton Hospital
state: New Brunswick
city: Halifax
country: Canada
facility: Atlantic Health Sciences Corp - Saint John Regional Hospital
state: Nova Scotia
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: UHN-Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: CHUM Hopital Notre-Dame
state: Quebec
city: Montreal
country: Canada
facility: McGill University Department of Oncology
state: Quebec
city: Quebec city
country: Canada
facility: Hôpital de l'Enfant-Jesus, CHU de Quebec
state: Quebec
city: Saskatoon
country: Canada
facility: Saskatoon Cancer Centre
state: Saskatchewan
city: Lille
country: France
facility: CHU Claude Huriez
city: Tübingen
country: Germany
facility: Medizinische Klinik der Universität Tübingen
state: Baden Wurtemberg
city: Köln
country: Germany
facility: Uniklinik Köln
state: Nordrhein
city: Munchen
country: Germany
facility: LMU Munchën - Klinikum Grosshadern
city: Roma
country: Italy
facility: Sant'Andrea Hospital
state: Lazio
city: Bologna
country: Italy
facility: Policlinico Sant'Orsola-Malpighi
city: Lisboa
country: Portugal
facility: Instituto Português Oncologia
city: Sevilla
country: Spain
facility: Hospital Virgen del Rocio
state: Andaloucia
city: Terrassa
country: Spain
facility: Hospital Universitario Mutua de Terrassa
state: Barcelona
city: Santa Cruz de Tenerife
country: Spain
facility: Hospital Universitario de Canarias
state: Canarias
city: Palma
country: Spain
facility: Hospital Son Llatzer
state: Mallorca
city: Barcelona
country: Spain
facility: Hospital Clínico de Barcelona
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d´Hebron
city: Girona
country: Spain
facility: Institut Català d'Oncologia de Girona (ICO Girona)
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal
city: Marbella
country: Spain
facility: Hospital Costa del Sol
city: Salamanca
country: Spain
facility: Hospital Universitario Salamanca
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
Study officials:
affiliation: The Lymphoma Study Association (LYSA)
name: Franck Morschhauser, MD, PhD
role: STUDY_CHAIR
References:
citation: Morschhauser F, Nastoupil L, Feugier P, Schiano de Colella JM, Tilly H, Palomba ML, Bachy E, Fruchart C, Libby EN, Casasnovas RO, Flinn IW, Haioun C, Maisonneuve H, Ysebaert L, Bartlett NL, Bouabdallah K, Brice P, Ribrag V, Le Gouill S, Daguindau N, Guidez S, Pica GM, Garcia-Sancho AM, Lopez-Guillermo A, Larouche JF, Ando K, Gomes da Silva M, Andre M, Kalung W, Sehn LH, Izutsu K, Cartron G, Gkasiamis A, Crowe R, Xerri L, Fowler NH, Salles G. Six-Year Results From RELEVANCE: Lenalidomide Plus Rituximab (R2) Versus Rituximab-Chemotherapy Followed by Rituximab Maintenance in Untreated Advanced Follicular Lymphoma. J Clin Oncol. 2022 Oct 1;40(28):3239-3245. doi: 10.1200/JCO.22.00843. Epub 2022 Aug 10.
citation: Delfau-Larue MH, Boulland ML, Beldi-Ferchiou A, Feugier P, Maisonneuve H, Casasnovas RO, Lemonnier F, Pica GM, Houot R, Ysebaert L, Tilly H, Eisenmann JC, Le Gouill S, Ribrag V, Godmer P, Glaisner S, Cartron G, Xerri L, Salles GA, Fest T, Morschhauser F. Lenalidomide/rituximab induces high molecular response in untreated follicular lymphoma: LYSA ancillary RELEVANCE study. Blood Adv. 2020 Aug 11;4(14):3217-3223. doi: 10.1182/bloodadvances.2020001955.
citation: Morschhauser F, Fowler NH, Feugier P, Bouabdallah R, Tilly H, Palomba ML, Fruchart C, Libby EN, Casasnovas RO, Flinn IW, Haioun C, Maisonneuve H, Ysebaert L, Bartlett NL, Bouabdallah K, Brice P, Ribrag V, Daguindau N, Le Gouill S, Pica GM, Martin Garcia-Sancho A, Lopez-Guillermo A, Larouche JF, Ando K, Gomes da Silva M, Andre M, Zachee P, Sehn LH, Tobinai K, Cartron G, Liu D, Wang J, Xerri L, Salles GA; RELEVANCE Trial Investigators. Rituximab plus Lenalidomide in Advanced Untreated Follicular Lymphoma. N Engl J Med. 2018 Sep 6;379(10):934-947. doi: 10.1056/NEJMoa1805104.