Rituximab Plus Lenalidomide for Patients With Relapsed / Refractory Indolent Non-Hodgkin's Lymphoma (Follicular Lymphoma and Marginal Zone Lymphoma)

NCT ID: NCT01938001

Last Updated: 2023-02-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 358 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-11-21
• Study Completion Date: 2022-01-26

Brief Summary

This double-blind randomized, parallel group study will evaluate the efficacy and safety of lenalidomide (Revlimid, CC-5013) in combination with rituximab (MabThera/Rituxan) in patients with relapsed or refractory follicular lymphoma or marginal zone lymphoma. Patients will be randomized to receive either lenalidomide or placebo for twelve 28-day cycles in combination with rituximab. Anticipated time on study treatment is 1 year.

Detailed Description

Indolent lymphoma is a slow growing but incurable lymphoma which includes follicular lymphoma and marginal zone lymphoma. Follicular lymphoma and marginal zone lymphoma are cancers of the B lymphocyte, a type of white blood cell. Lenalidomide is an immunomodulatory drug (a drug that affects the immune system) which alters the body's immune system and it may also interfere with the development of tiny blood vessels involved in tumor growth. Therefore, lenalidomide may reduce or prevent the growth of cancer cells. Lenalidomide has also been shown to restore the immune cells' ability to attack and kill tumor cells, an ability that may be inhibited by follicular lymphoma and other lymphomas. The combination of rituximab and lenalidomide may eliminate the cancer while restoring the immune system's ability to attack tumor cells.

Conditions

Lymphoma, Non-Hodgkin

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Rituximab and Lenalidomide

Participants received rituximab 375 mg/m\^2 intravenously (IV) every week in Cycle 1 (Days 1, 8, 15 and 22) and on Day 1 of every 28-day cycle from Cycles 2 to 5 plus lenalidomide 20 mg by mouth (PO) once daily on Days 1 to 21 every 28 days, up to 12 cycles (21-day treatment and 7-day rest period); if creatinine clearance (CrCl) was ≥ 30 mL/min but \< 60 mL/min, participants received lenalidomide 10 mg capsules on days 1 to 21 every 28 days.

Group Type: EXPERIMENTAL

Rituximab

Intervention Type: DRUG

Rituximab 375mg/m\^2 IV every week in Cycle 1 (Days 1, 8, 15 and 22) on Day 1 of every 28 day cycle from Cycles 2 to 5

Lenalidomide

Intervention Type: DRUG

Lenalidomide 20mg by mouth (PO) daily on Days 1 to 21 every 28 days up to 12 cycles

Rituximab and Placebo

Participants received riituximab 375 mg/m\^2 IV every week in Cycle 1 (Days 1, 8, 15 and 22) and on Day 1 of every 28-day cycle from cycle 2 to 5 plus placebo (identically matched capsule) once daily on Days 1 to 21 of every 28-day cycle up, to 12 cycles.

Group Type: ACTIVE_COMPARATOR

Rituximab

Intervention Type: DRUG

Rituximab 375mg/m\^2 IV every week in Cycle 1 (Days 1, 8, 15 and 22) on Day 1 of every 28 day cycle from Cycles 2 to 5

Placebo

Intervention Type: DRUG

Placebo (identical matched capsule) PO daily on Days 1 to 21 every 28 days

Interventions

Rituximab

Rituximab 375mg/m\^2 IV every week in Cycle 1 (Days 1, 8, 15 and 22) on Day 1 of every 28 day cycle from Cycles 2 to 5

Intervention Type: DRUG

Lenalidomide

Lenalidomide 20mg by mouth (PO) daily on Days 1 to 21 every 28 days up to 12 cycles

Intervention Type: DRUG

Placebo

Placebo (identical matched capsule) PO daily on Days 1 to 21 every 28 days

Intervention Type: DRUG

Other Intervention Names

Rituxan; CC-5013, Revlimid

Eligibility Criteria

Inclusion Criteria

• Age ≥18 years at the time of signing the informed consent document.
• Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures are conducted.
• Histologically confirmed marginal zone lymphoma or follicular lymphoma (grade 1, 2 or 3a; CD20+ by flow cytometry or histochemistry).
• Previously treated with at least one prior systemic chemotherapy, immunotherapy or chemoimmunotherapy and have received at least 2 previous doses of rituximab.
• Documented relapsed, refractory or progressive disease after treatment with systemic therapy and must not be rituximab-refractory.
• Investigator considers rituximab monotherapy appropriate.
• Bi-dimensionally measurable disease on cross sectional imaging by X-ray computed tomography (CT) or magnetic resonance imaging (MRI).
• Need of treatment for relapsed, progressed or refractory disease as assessed by the investigator.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Adequate bone marrow function.
• Willingness to follow study visit schedule, pregnancy precautions and other protocol requirements.

Exclusion Criteria

• Histology other than follicular or marginal zone lymphoma or clinical evidence of transformation or Grade 3b follicular lymphoma.
• Subjects taking corticosteroids during the last week prior to study treatment, unless administered at a dose equivalent to < 20 mg/day prednisone or prednisolone.
• Systemic anti-lymphoma therapy within 28 days or use of antibody agents within 8 weeks use of radioimmunotherapy within 6 months.
• Known seropositive for or active viral infection with hepatitis B virus (HBV) or/and human immunodeficiency virus (HIV).
• Known hepatitis C virus (HCV) positive with chronic HCV or active viral infection with HCV hepatitis requiring anti-viral medication (at time of randomization).
• Life expectancy < 6 months.
• Known sensitivity or allergy to murine products.
• Prior history of malignancies, other than follicular or marginal zone lymphoma, unless the subject has been free of the disease for ≥ 5 years.
• Prior use of lenalidomide.
• Known allergy to thalidomide.
• Neuropathy > Grade 1.
• Presence or history of central nervous system involvement by lymphoma.
• Subjects who are at a risk for a thromboembolic event and are not willing to take prophylaxis for it.
• Uncontrolled intercurrent illness.
• Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent document.
• Pregnant or lactating females.
• Any condition that places the subject at unacceptable risk if he/she were to participate in the study or that confounds the ability to interpret data from the study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Celgene

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

Mitchell Cancer Center, University of South Alabama

Mobile, Alabama, United States

Arizona Center for Cancer Care

Glendale, Arizona, United States

Southwest Cancer Care Medical Group

Escondido, California, United States

Marin Oncology Associates

Greenbrae, California, United States

Wilshire Oncology Medical Group, Inc

La Verne, California, United States

North County Hematology Oncology (NCHO) - TRM, LLC.

Oceanside, California, United States

Hematology-Oncology Medical Group of Orange County, Inc.

Orange, California, United States

UC Davis Medical Center

Sacramento, California, United States

Central Coast Medical Oncology Corporation

Santa Maria, California, United States

Wellness Hematology Oncology

West Hills, California, United States

Cancer Center of Central Connecticut

Southington, Connecticut, United States

Florida Cancer Specialists North Region Sarah Cannon Research

St. Petersburg, Florida, United States

Illinois Cancer Care, P.C.

Peoria, Illinois, United States

LRG Healthcare Oncology Clinic

Laconia, Indiana, United States

Iowa Oncology Research Association

Des Moines, Iowa, United States

University of Louisville, J.G. Brown Cancer Center

Louisville, Kentucky, United States

Providence Cancer Institute

Southfield, Michigan, United States

Mayo Clinic

Rochester, Minnesota, United States

Coborn Cancer Center at the St. Cloud Hospital

Saint Cloud, Minnesota, United States

NH Oncology - Hematology, PA

Hooksett, New Hampshire, United States

The Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, United States

Hematology-Oncology Associates of Northern NJ

Morristown, New Jersey, United States

University of New Mexico

Albuquerque, New Mexico, United States

Weill Cornell Medical College

New York, New York, United States

SUNY Upstate Medical University

Syracuse, New York, United States

Wake Forest Baptist Health

Winston-Salem, North Carolina, United States

Oncology Hematology Care Sarah Cannon Research

Cincinnati, Ohio, United States

Local Institution - 028

Portland, Oregon, United States

Providence Portland Medical Center

Portland, Oregon, United States

St Francis Hospital

Greenville, South Carolina, United States

Spartanburg Regional Healthcare System - Gibbs Cancer Center & Research Institute

Spartanburg, South Carolina, United States

Sarah Cannon Research Inst

Nashville, Tennessee, United States

Arlington Cancer Center

Arlington, Texas, United States

MD Anderson Cancer Center

Houston, Texas, United States

Northwest Medical Specialties PLLC

Tacoma, Washington, United States

AZ St-Jan Brugge Oostende AV

Bruges, , Belgium

Local Institution - 371

Ghent, , Belgium

UZ Gent

Ghent, , Belgium

AZ Groeninge

Kortrijk, , Belgium

CHU Mont -Godinne

Yvoir, , Belgium

Associacao Hospitalar Moinhos de Vento Hospital Moinhos de Vento

Porto Alegre, Rio Grande do Sul, Brazil

Hospital de Clínicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da PUCRS

Porto Alegre, Rio Grande do Sul, Brazil

Associacao Educudora Sao Carlos AESC Hospital Giovanni Battista HGB Hospital Mae de Deus Center

Porto Alegre, Rio Grande do Sul, Brazil

Fundacao Pio XII - Hospital de Cancer de Barretos

Barretos, São Paulo, Brazil

Hospital Dr. Amaral Carvalho/ Hospital Amaral Carvalho Jaú

Jau/SP, São Paulo, Brazil

MS INCA HC I Hospital do Cancer I

Rio de Janeiro, , Brazil

Sociedade Beneficente de Senhoras Hospital Sirio Libanes

São Paulo, , Brazil

Real e Benemerita Associacao Portuguesa de Beneficencia

São Paulo, , Brazil

Fundação Antonio Prudente - AC Camargo Câncer center

São Paulo, , Brazil

Peking University People's Hospital

Beijing, , China

307 Hospital of PLA

Beijing, , China

Peking Union Medical College Hospital

Beijing, , China

Beijing Cancer Hospital

Beijing, PR, , China

The Third Xiangya hospital of central south university

Changsha, , China

West China Hospital of Sichuan University

Chengdu, , China

Fujian Medical University Union Hospital

Fuzhou, , China

Sun Yat-sen University Cancer Center

Guangzhou, , China

Guangdong General Hospital

Guangzhou, , China

Local Institution - 600

Guangzhou, , China

The First Affiliated Hospital of Medical School of Zhejiang University

Hangzhou, , China

Local Institution - 604

Hangzhou, , China

Jiangsu Province Hospital The First Hospital affiliated with Nanjing Medical University

Nanjing, , China

Cancer Hospital, Fudan University

Shanghai, , China

Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Shanghai, , China

The First Affiliated Hospital of Soochow University

Suzhou, , China

Chinese Academy of Medical Sciences & Peking Union Medical College

Tianjin, , China

Tianjin Medical University Cancer Institute and Hospital

Tianjin, , China

Xijing Hospital

Xi'an, , China

Interni hematoonkologicka klinika

Brno, , Czechia

Fakultni nemocnice Hradec Kralove, IV.interni hematologicka klinika

Hradec Králové, , Czechia

Fakultni Nemocnice Ostrava, Klinika hematoonkologie,

Ostrava, , Czechia

Fakultni nemocnice Kralovske Vinohrady, Interni hematologicka klinika

Prague, , Czechia

Local Institution - 534

Prague, , Czechia

Vseobecna Fakultni Nemocnice v Praze

Prague, , Czechia

CHU d'Angers

Angers, , France

Centre Hospitalier Universitaire d'Avicennes

Bobigny, , France

CHRU de Brest - Hopital Morvan

Brest, , France

Hopital Saint-Louis

Paris, , France

CH Perpignan - Hopital Saint-Jean

Perpignan, , France

CHU de Poitiers

Poitiers, , France

Centre Hospitalier de Valence

Valence, , France

Charite - Universitaetsmedizin Berlin Charité - Campus Benjamin Franklin

Berlin, , Germany

Charite - Universitaetsmedizin Berlin Campus Virchow Klinikum

Berlin, , Germany

Krankenhaus Nordwest

Frankfurt, , Germany

Onkologische Schwerpunktpraxis Leer - Emden

Leer, , Germany

Kliniken Maria Hilf GmbH

Mönchengladbach, , Germany

Klinkum der Stadt Villingen-Schwenningen GmbH

Villingen-Schwenningen, , Germany

Soroka University Medical Center

Beersheba, , Israel

Hadassah University Hospital

Jerusalem, , Israel

Tel-Aviv Sourasky Medical Center

Tel Aviv, , Israel

Centro di Riferimento Oncologico - IRCCS

Aviano (PN), , Italy

U.O.C. Ematologia

Barletta, , Italy

A.O.U. di Bologna Policlinico S.Orsola-Malpighi

Bologna, , Italy

Azienda Ospedaliera di Rilievo Nazionale e di Alta Specializzazione Garibaldi - Nesima

Catania, , Italy

Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori (I.R.S.T.)

Meldola, , Italy

Istituto Europeo di Oncologia - IEO

Milan, , Italy

Ospedale Niguarda Ca Granda

Milan, , Italy

IRCCS- Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione "G. Pascale"

Napoli, , Italy

Az. Osp. Vincenzo Cervello

Palermo, , Italy

Casa di Cura La Maddalena

Palermo, , Italy

Azienda Ospedaliero-Universitaria di Parma

Parma, , Italy

Ospedale di Ravenna

Ravenna, , Italy

Azienda Ospedaliera Bianchi-Melacrino-Morelli

Reggio Calabria, , Italy

Ospedale degli Infermi di Rimini

Rimini, , Italy

Azienda Ospedaliera S. Andrea - Università La Sapienza

Roma, , Italy

Local Institution - 340

Roma, , Italy

Local Institution - 708

Nagasaki, Nagasaki, Japan

Local Institution - 709

Minato-ku, Tokyo, Japan

National Cancer Center Hospital

Chūōku, , Japan

Chugoku Central Hospital

Hiroshima, , Japan

National Cancer Center Hospital East

Kashiwa, , Japan

Kobe City Medical Center General Hospital

Kobe, , Japan

The Cancer Institute Hospital of Japanese Foundation For Cancer Research

Kōtoku, , Japan

Local Institution - 700

Kōtoku, , Japan

University Hospital, Kyoto Prefectural University of Medicine

Kyoto, , Japan

Toranomon Hospital

Minatoku, , Japan

The Japanese Red Cross Nagasaki Genbaku Hospital

Nagasaki, , Japan

Nagoya Medical Center,Division of Hematology/Oncology

Nagoya, , Japan

National University Corporation Tohoku University, Tohoku University Hospital

Sendai, , Japan

Malopolskie Centrum Medyczne S.C.

Krakow, , Poland

Instytut Hematologii i Transfuzjologii w Warszawie

Warsaw, , Poland

Local Institution - 514

Warsaw, , Poland

Centrum Onkologii, Instytut im. Marii Sklodowskiej-Curie

Warsaw, , Poland

Local Institution - 513

Warsaw, , Poland

Instituto Portugues de Oncologia de Lisboa, Francisco Gentil

Lisbon, , Portugal

Local Institution - 330

Lisbon, , Portugal

Instituto Portugues de Oncologia do Porto, Francisco Gentil

Porto, , Portugal

Local Institution - 331

Porto, , Portugal

Hospital Auxilio Muto Centro de Cancer

San Juan, , Puerto Rico

Krasnoyarsk Regional Clinical Hospital

Krasnoyarsk, , Russia

Russian Academy of Medical Sciences Institution

Moscow, , Russia

Moscow State Medical Institution Municipal Clinical Hospital n.a. S.P. Botkin

Moscow, , Russia

St. Petersburg Pavlov State Medical University

Saint Petersburg, , Russia

Federal Centre of Heart, Blood and Endocrinology of Rosmed technlologies V.A. Almazov

Saint Petersburg, , Russia

The Ministry of Health and Social Development of the Tula region state institution Health Tula regio

Tula, , Russia

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Hospital Universitario Reina Sofia

Córdoba, , Spain

Local Institution - 314

Córdoba, , Spain

Hospital Universitario Infanta Leonor

Madrid, , Spain

Hospital Universitario Fundacion Jimenez Diaz

Madrid, , Spain

Hospital Costa del Sol

Marbella, , Spain

Local Institution - 315

Marbella, , Spain

Hospital Morales Meseguer

Murcia, , Spain

Local Institution - 318

Murcia, , Spain

Hospital Universitario de Salamanca

Salamanca, , Spain

Local Institution - 311

Salamanca, , Spain

Hospital Universitario Virgen Del Rocio

Seville, , Spain

Cukurova University Medical Faculty Balcali Hospital

Adana, , Turkey (Türkiye)

Hacettepe Universitesi

Ankara, , Turkey (Türkiye)

Pamukkale University Medical Faculty

Denizli, , Turkey (Türkiye)

Gaziantep University

Gaziantep, , Turkey (Türkiye)

Marmara University

Istanbul, , Turkey (Türkiye)

Dokuz Eylul University Izmir

Izmir, , Turkey (Türkiye)

19 Mayis Medical Faculty - Samsun

Samsun, , Turkey (Türkiye)

Kocaeli Derince Training and Research Hospital

Umuttepe Kocaeli, , Turkey (Türkiye)

Eastbourne District General Hospital

Eastbourne, , United Kingdom

Royal Liverpool University Hospital, Prescot Street

Liverpool, , United Kingdom

Barts Cancer Institute, Queen Mary University of London, Charterhouse Square

London, , United Kingdom

Southend University Hospital NHS Foundation Trust, Prittlewell Chase

Westcliff-on-Sea, , United Kingdom

Countries

United States; Belgium; Brazil; China; Czechia; France; Germany; Israel; Italy; Japan; Poland; Portugal; Puerto Rico; Russia; Spain; Turkey (Türkiye); United Kingdom

References

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.

Reference Type: BACKGROUND

PMID: 30184451 (View on PubMed)

Leonard JP, Trneny M, Izutsu K, Fowler NH, Hong X, Zhu J, Zhang H, Offner F, Scheliga A, Nowakowski GS, Pinto A, Re F, Fogliatto LM, Scheinberg P, Flinn IW, Moreira C, Cabecadas J, Liu D, Kalambakas S, Fustier P, Wu C, Gribben JG; AUGMENT Trial Investigators. AUGMENT: A Phase III Study of Lenalidomide Plus Rituximab Versus Placebo Plus Rituximab in Relapsed or Refractory Indolent Lymphoma. J Clin Oncol. 2019 May 10;37(14):1188-1199. doi: 10.1200/JCO.19.00010. Epub 2019 Mar 21.

Reference Type: RESULT

PMID: 30897038 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html

BMS Clinical Trial Information

https://www.bmsstudyconnect.com/s/US/English/USenHome

BMS Clinical Trial Patient Recruiting

http://www.fda.gov/safety/medwatch/safetyinformation/default.htm

FDA Safety Alerts and Recalls

Other Identifiers

CC-5013-NHL-007

Identifier Type: -

Identifier Source: org_study_id