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

NCT01650701 | Completed Phase 3 DMC

• 2 other identifiers: RV-FOL-GELARC-06832011-002792-42
• Study Type: interventional
• Target: 1,030
• Locations: 8 countries
• Sites: 35

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.

Conditions

Follicular Lymphoma

Keywords

follicular lymphoma; non-hodgkins follicular lymphoma; treatment for follicular lymphoma; rituximab treatment; rituximab and lenalidomide treatment

Outcome Measures

Primary Outcomes (2)

• COMPLETE RESPONSE RATE

  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.

  Timeframe: CR/CRu rate at 120 weeks

• Progression Free Survival (PFS)

  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.

  up to 13 years

Secondary Outcomes (8)

• 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

• Time to Next Chemotherapy Treatment (TTNCT)

  up to13 years

Study Arms (2)

Lenalidomide + Rituximab

EXPERIMENTAL

* 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.

Drug: Rituximab; Drug: Lenalidomide

Control

ACTIVE COMPARATOR

• 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; Drug: Rituximab - CVP; Drug: Rituximab - Bendamustine

Interventions

Rituximab DRUG

• 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.

Also known as: mabthera, rituxan

Lenalidomide + Rituximab

Lenalidomide DRUG

• 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

Also known as: Revlimid

Lenalidomide + Rituximab

Rituximab - CHOP DRUG

six cycles of R-CHOP in 21 day cycles followed by two 21 day cycles of 375 mg/m2 rituximab; and 7 weeks later responding patients continue with 375 mg/m2 rituximab every 8 weeks for 12 cycles

Control

Rituximab - CVP DRUG

eight cycles of R-CVP in 21 day cycles; and 7 weeks later responding patients continue with 375 mg/m2 rituximab every 8 weeks for 12 cycles,

Control

Rituximab - Bendamustine DRUG

six cycles of R-B in 28 day cycles and 8 weeks later responding patients continue with 375 mg/m2 rituximab every 8 weeks for 12 cycles.

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• The Lymphoma Academic Research Organisation: lead
• Celgene Corporation: collaborator

Study Sites (35)

Concord Repatriation General Hospital

Concord, New South Wales, Australia

Location

Nepean Hospital

Penrith, New South Wales, Australia

Location

Wollongong Hospital

Wollongong, New South Wales, Australia

Location

CHU Mont-Godinne

Yvoir, Belgium

Location

Tom Baker Cancer Centre

Calgary, Alberta, Canada

Location

Cross Cancer Institute

Edmonton, Alberta, Canada

Location

Fraser Valley Cancer Centre

Surrey, British Columbia, Canada

Location

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, Canada

Location

Moncton Hospital

Moncton, New Brunswick, Canada

Location

Atlantic Health Sciences Corp - Saint John Regional Hospital

Halifax, Nova Scotia, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Location

UHN-Princess Margaret Hospital

Toronto, Ontario, Canada

Location

CHUM Hopital Notre-Dame

Montreal, Quebec, Canada

Location

McGill University Department of Oncology

Montreal, Quebec, Canada

Location

Hôpital de l'Enfant-Jesus, CHU de Quebec

Québec, Quebec, Canada

Location

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, Canada

Location

CHU Claude Huriez

Lille, France

Location

Medizinische Klinik der Universität Tübingen

Tübingen, Baden-Wurttemberg, Germany

Location

Uniklinik Köln

Cologne, Nordrhein, Germany

Location

LMU Munchën - Klinikum Grosshadern

München, Germany

Location

Sant'Andrea Hospital

Rome, Lazio, Italy

Location

Policlinico Sant'Orsola-Malpighi

Bologna, Italy

Location

Instituto Português Oncologia

Lisbon, Portugal

Location

Hospital Virgen del Rocio

Seville, Andaloucia, Spain

Location

Hospital Universitario Mutua de Terrassa

Terrassa, Barcelona, Spain

Location

Hospital Universitario de Canarias

Santa Cruz de Tenerife, Canary Islands, Spain

Location

Hospital Son Llatzer

Palma, Mallorca, Spain

Location

Hospital Clínico de Barcelona

Barcelona, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain

Location

Hospital Universitario Vall d´Hebron

Barcelona, Spain

Location

Institut Català d'Oncologia de Girona (ICO Girona)

Girona, Spain

Location

Hospital Ramon y Cajal

Madrid, Spain

Location

Hospital Costa del Sol

Marbella, Spain

Location

Hospital Universitario Salamanca

Salamanca, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, Spain

Location

Related Publications (5)

• Claudel A, Cottereau AS, Bachy E, Itti E, Feugier P, Rossi C, Lemonnier F, Camus V, Daguindau N, Cartron G, Nicolas-Virelizier E, Mboumba DL, Cardoso C, Bommier C, Tessoulin B, Fruchart C, Gilbert A, Durot E, Fleck E, Pica GM, Zerazhi H, Guidez S, Cheminant M, Sarkozy C, Xerri L, Vercellino L, Trabelsi N, Gomes L, Portugues C, Viailly PJ, Delfau-Larue MH, Morschhauser F. Combined PET and ctDNA response as a predictor of POD24 for follicular lymphoma after first-line induction treatment. Blood. 2025 Aug 21;146(8):913-925. doi: 10.1182/blood.2024027727.

  PMID: 40499012 DERIVED

• Laurent C, Trisal P, Tesson B, Seth S, Beyou A, Roulland S, Lesne B, Van Acker N, Cerapio JP, Chartier L, Guille A, Stokes ME, Huang CC, Huet S, Gandhi AK, Morschhauser F, Xerri L. Follicular lymphoma comprises germinal center-like and memory-like molecular subtypes with prognostic significance. Blood. 2024 Dec 12;144(24):2503-2516. doi: 10.1182/blood.2024024496.

  PMID: 39374535 DERIVED

• 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.

  PMID: 35947804 DERIVED

• 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.

  PMID: 32673385 DERIVED

• 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.

  PMID: 30184451 DERIVED

MeSH Terms

Conditions

Lymphoma, Follicular

Interventions

Rituximab; Lenalidomide

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Franck Morschhauser, MD, PhD

  The Lymphoma Study Association (LYSA)

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2012
• First Posted: July 26, 2012
• Study Start: February 1, 2012
• Primary Completion: May 31, 2017
• Study Completion: April 30, 2024
• Last Updated: September 25, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CA (12); BE (1); FR (1); ES (12); AU (3); DE (3); PT (1); IT (2)