Rituximab Plus Lenalidomide for Patients With Relapsed / Refractory Indolent Non-Hodgkin's Lymphoma (Follicular Lymphoma and Marginal Zone Lymphoma)
AUGMENT
A Phase 3, Double-blind, Randomized Study to Compare the Efficacy and Safety of Rituximab Plus Lenalidomide (CC-5013) Versus Rituximab Plus Placebo in Subjects With Relapsed/Refractory Indolent Lymphoma
1 other identifier
interventional
358
17 countries
160
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Nov 2013
Longer than P75 for phase_3
160 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 5, 2013
CompletedFirst Posted
Study publicly available on registry
September 10, 2013
CompletedStudy Start
First participant enrolled
November 21, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 22, 2018
CompletedResults Posted
Study results publicly available
August 13, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
January 26, 2022
CompletedFebruary 22, 2023
January 1, 2023
4.6 years
September 5, 2013
June 21, 2019
January 26, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Kaplan Meier Estimate of Progression Free Survival Assessed by the Independent Review Committee (IRC) According to the 2007 International Working Group Response Criteria (IWGRC)
Progression-free survival (PFS) was defined as the time from date of randomization into the study to the first observation of documented disease progression or death due to any cause, whichever occurred first. PFS was based on the data from the IRC review using the modified 2007 International Working Group Response Criteria (IWGRC) using FDA censoring rules.
From randomization of study drug up to disease progression or death, which occurred first; up to the data cut-off date of 22 June 2018; overall median follow-up time for all participants was 28.30 months (range: 0.1 to 51.3 months).
Secondary Outcomes (9)
Durable Complete Response Rate (DCCR) as Assessed by the IRC According to the 2007 IWGRC
From first dose of investigational product (IP) to data cut-off date of 22 June 2018; the median treatment duration was 11.19 months in the rituximab/lenalidomiade arm and 11.04 months in the rituximab/placebo arm
Kaplan-Meier Estimate of Overall Survival (OS)
From date of randomization to death due to any cause (Average of 55.71 months and a maximum up to 95.2 months)
Percentage of Participants With an Objective Response as Assessed by the IRC According to the 2007 IWGRC
From date of first dose to data cut-off date of 22 June 2018; the median treatment duration was 11.19 months in the rituximab/lenalidomide arm and 11.04 months in the rituximab/placebo arm
Percentage of Participants With a Best Response of Complete Response as Assessed by the IRC According to the 2007 IWGRC
From date of first dose up to data cut-off date of 22 June 2018; the median treatment duration was 11.19 months in the rituximab/lenalidomide arm and 11.04 months in the rituximab/placebo arm
Kaplan-Meier Estimate of Duration of Objective Response as Assessed by the IRC According to the 2007 IWGRC
From randomization up to data cut-off date of 22 June 2018; overall median follow-up time for all participants was 28.30 months (range: 0.1 to 51.3 months).
- +4 more secondary outcomes
Study Arms (2)
Rituximab and Lenalidomide
EXPERIMENTALParticipants 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.
Rituximab and Placebo
ACTIVE COMPARATORParticipants 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.
Interventions
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 20mg by mouth (PO) daily on Days 1 to 21 every 28 days up to 12 cycles
Placebo (identical matched capsule) PO daily on Days 1 to 21 every 28 days
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Celgenelead
Study Sites (160)
Mitchell Cancer Center, University of South Alabama
Mobile, Alabama, 36604, United States
Arizona Center for Cancer Care
Glendale, Arizona, 85306, United States
Southwest Cancer Care Medical Group
Escondido, California, 92025, United States
Marin Oncology Associates
Greenbrae, California, 94904-2007, United States
Wilshire Oncology Medical Group, Inc
La Verne, California, 91750, United States
North County Hematology Oncology (NCHO) - TRM, LLC.
Oceanside, California, 92056, United States
Hematology-Oncology Medical Group of Orange County, Inc.
Orange, California, 92868, United States
UC Davis Medical Center
Sacramento, California, 95817, United States
Central Coast Medical Oncology Corporation
Santa Maria, California, 93454, United States
Wellness Hematology Oncology
West Hills, California, 92056, United States
Cancer Center of Central Connecticut
Southington, Connecticut, 06489, United States
Florida Cancer Specialists North Region Sarah Cannon Research
St. Petersburg, Florida, 33705, United States
Illinois Cancer Care, P.C.
Peoria, Illinois, 61615, United States
LRG Healthcare Oncology Clinic
Laconia, Indiana, 03246, United States
Iowa Oncology Research Association
Des Moines, Iowa, 50309, United States
University of Louisville, J.G. Brown Cancer Center
Louisville, Kentucky, 40202, United States
Providence Cancer Institute
Southfield, Michigan, 48075, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
Coborn Cancer Center at the St. Cloud Hospital
Saint Cloud, Minnesota, 56303, United States
NH Oncology - Hematology, PA
Hooksett, New Hampshire, 03106, United States
The Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
Hematology-Oncology Associates of Northern NJ
Morristown, New Jersey, 07962, United States
University of New Mexico
Albuquerque, New Mexico, 87102, United States
Weill Cornell Medical College
New York, New York, 10065, United States
SUNY Upstate Medical University
Syracuse, New York, 13210, United States
Wake Forest Baptist Health
Winston-Salem, North Carolina, 27157, United States
Oncology Hematology Care Sarah Cannon Research
Cincinnati, Ohio, 45242, United States
Local Institution - 028
Portland, Oregon, 97213, United States
Providence Portland Medical Center
Portland, Oregon, 97213, United States
St Francis Hospital
Greenville, South Carolina, 29607, United States
Spartanburg Regional Healthcare System - Gibbs Cancer Center & Research Institute
Spartanburg, South Carolina, 29303, United States
Sarah Cannon Research Inst
Nashville, Tennessee, 37203, United States
Arlington Cancer Center
Arlington, Texas, 76012, United States
MD Anderson Cancer Center
Houston, Texas, 77030, United States
Northwest Medical Specialties PLLC
Tacoma, Washington, 98405, United States
AZ St-Jan Brugge Oostende AV
Bruges, 8000, Belgium
Local Institution - 371
Ghent, 9000, Belgium
UZ Gent
Ghent, 9000, Belgium
AZ Groeninge
Kortrijk, 8500, Belgium
CHU Mont -Godinne
Yvoir, 5530, Belgium
Associacao Hospitalar Moinhos de Vento Hospital Moinhos de Vento
Porto Alegre, Rio Grande do Sul, 90035-001, Brazil
Hospital de Clínicas de Porto Alegre
Porto Alegre, Rio Grande do Sul, 90035-903, Brazil
Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da PUCRS
Porto Alegre, Rio Grande do Sul, 90610-000, Brazil
Associacao Educudora Sao Carlos AESC Hospital Giovanni Battista HGB Hospital Mae de Deus Center
Porto Alegre, Rio Grande do Sul, 90740-340, Brazil
Fundacao Pio XII - Hospital de Cancer de Barretos
Barretos, São Paulo, 14784-400, Brazil
Hospital Dr. Amaral Carvalho/ Hospital Amaral Carvalho Jaú
Jau/SP, São Paulo, 17210-080, Brazil
MS INCA HC I Hospital do Cancer I
Rio de Janeiro, 20231-130, Brazil
Sociedade Beneficente de Senhoras Hospital Sirio Libanes
São Paulo, 01308 050, Brazil
Real e Benemerita Associacao Portuguesa de Beneficencia
São Paulo, 01321-001, Brazil
Fundação Antonio Prudente - AC Camargo Câncer center
São Paulo, 01509-900, Brazil
Peking University People's Hospital
Beijing, 100044, China
307 Hospital of PLA
Beijing, 100071, China
Peking Union Medical College Hospital
Beijing, 100730, China
Beijing Cancer Hospital
Beijing, PR, 100142, China
The Third Xiangya hospital of central south university
Changsha, 410013, China
West China Hospital of Sichuan University
Chengdu, 610041, China
Fujian Medical University Union Hospital
Fuzhou, 350001, China
Sun Yat-sen University Cancer Center
Guangzhou, 510060, China
Guangdong General Hospital
Guangzhou, 510080, China
Local Institution - 600
Guangzhou, 510080, China
The First Affiliated Hospital of Medical School of Zhejiang University
Hangzhou, 310003, China
Local Institution - 604
Hangzhou, 310006, China
Jiangsu Province Hospital The First Hospital affiliated with Nanjing Medical University
Nanjing, 210029, China
Cancer Hospital, Fudan University
Shanghai, 200032, China
Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Shanghai, China
The First Affiliated Hospital of Soochow University
Suzhou, 215006, China
Chinese Academy of Medical Sciences & Peking Union Medical College
Tianjin, 300020, China
Tianjin Medical University Cancer Institute and Hospital
Tianjin, 300060, China
Xijing Hospital
Xi'an, 710032, China
Interni hematoonkologicka klinika
Brno, 625 00, Czechia
Fakultni nemocnice Hradec Kralove, IV.interni hematologicka klinika
Hradec Králové, 500 05, Czechia
Fakultni Nemocnice Ostrava, Klinika hematoonkologie,
Ostrava, 70852, Czechia
Fakultni nemocnice Kralovske Vinohrady, Interni hematologicka klinika
Prague, 100 34, Czechia
Local Institution - 534
Prague, 128 08, Czechia
Vseobecna Fakultni Nemocnice v Praze
Prague, 128 08, Czechia
CHU d'Angers
Angers, 49033, France
Centre Hospitalier Universitaire d'Avicennes
Bobigny, 93009, France
CHRU de Brest - Hopital Morvan
Brest, 29609, France
Hopital Saint-Louis
Paris, 75010, France
CH Perpignan - Hopital Saint-Jean
Perpignan, 66046, France
CHU de Poitiers
Poitiers, 86021, France
Centre Hospitalier de Valence
Valence, 26953, France
Charite - Universitaetsmedizin Berlin Charité - Campus Benjamin Franklin
Berlin, 12203, Germany
Charite - Universitaetsmedizin Berlin Campus Virchow Klinikum
Berlin, 13353, Germany
Krankenhaus Nordwest
Frankfurt, 60488, Germany
Onkologische Schwerpunktpraxis Leer - Emden
Leer, 26789, Germany
Kliniken Maria Hilf GmbH
Mönchengladbach, 41063, Germany
Klinkum der Stadt Villingen-Schwenningen GmbH
Villingen-Schwenningen, 78052, Germany
Soroka University Medical Center
Beersheba, 84101, Israel
Hadassah University Hospital
Jerusalem, 91120, Israel
Tel-Aviv Sourasky Medical Center
Tel Aviv, 64239, Israel
Centro di Riferimento Oncologico - IRCCS
Aviano (PN), 33081, Italy
U.O.C. Ematologia
Barletta, 76121, Italy
A.O.U. di Bologna Policlinico S.Orsola-Malpighi
Bologna, 40138, Italy
Azienda Ospedaliera di Rilievo Nazionale e di Alta Specializzazione Garibaldi - Nesima
Catania, 95124, Italy
Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori (I.R.S.T.)
Meldola, 47014, Italy
Istituto Europeo di Oncologia - IEO
Milan, 20141, Italy
Ospedale Niguarda Ca Granda
Milan, 20162, Italy
IRCCS- Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione "G. Pascale"
Napoli, 80131, Italy
Az. Osp. Vincenzo Cervello
Palermo, 90146, Italy
Casa di Cura La Maddalena
Palermo, 90146, Italy
Azienda Ospedaliero-Universitaria di Parma
Parma, 43100, Italy
Ospedale di Ravenna
Ravenna, 48121, Italy
Azienda Ospedaliera Bianchi-Melacrino-Morelli
Reggio Calabria, 89100, Italy
Ospedale degli Infermi di Rimini
Rimini, 47900, Italy
Azienda Ospedaliera S. Andrea - Università La Sapienza
Roma, 00189, Italy
Local Institution - 340
Roma, 00189, Italy
Local Institution - 708
Nagasaki, Nagasaki, 852-8511, Japan
Local Institution - 709
Minato-ku, Tokyo, 105-8470, Japan
National Cancer Center Hospital
Chūōku, 104-0045, Japan
Chugoku Central Hospital
Hiroshima, 7200001, Japan
National Cancer Center Hospital East
Kashiwa, 277-8577, Japan
Kobe City Medical Center General Hospital
Kobe, 650-0047, Japan
The Cancer Institute Hospital of Japanese Foundation For Cancer Research
Kōtoku, 135-8550, Japan
Local Institution - 700
Kōtoku, 1350063, Japan
University Hospital, Kyoto Prefectural University of Medicine
Kyoto, 602-8566, Japan
Toranomon Hospital
Minatoku, 105-8470, Japan
The Japanese Red Cross Nagasaki Genbaku Hospital
Nagasaki, 852-8511, Japan
Nagoya Medical Center,Division of Hematology/Oncology
Nagoya, 460-0001, Japan
National University Corporation Tohoku University, Tohoku University Hospital
Sendai, 980-8574, Japan
Malopolskie Centrum Medyczne S.C.
Krakow, 30-510, Poland
Instytut Hematologii i Transfuzjologii w Warszawie
Warsaw, 02-776, Poland
Local Institution - 514
Warsaw, 02-776, Poland
Centrum Onkologii, Instytut im. Marii Sklodowskiej-Curie
Warsaw, 02-781, Poland
Local Institution - 513
Warsaw, 02-781, Poland
Instituto Portugues de Oncologia de Lisboa, Francisco Gentil
Lisbon, 1099-023, Portugal
Local Institution - 330
Lisbon, 1099-023, Portugal
Instituto Portugues de Oncologia do Porto, Francisco Gentil
Porto, 4200-072, Portugal
Local Institution - 331
Porto, 4200-072, Portugal
Hospital Auxilio Muto Centro de Cancer
San Juan, 00918, Puerto Rico
Krasnoyarsk Regional Clinical Hospital
Krasnoyarsk, 660022, Russia
Russian Academy of Medical Sciences Institution
Moscow, 115478, Russia
Moscow State Medical Institution Municipal Clinical Hospital n.a. S.P. Botkin
Moscow, 125101, Russia
St. Petersburg Pavlov State Medical University
Saint Petersburg, 197022, Russia
Federal Centre of Heart, Blood and Endocrinology of Rosmed technlologies V.A. Almazov
Saint Petersburg, 197341, Russia
The Ministry of Health and Social Development of the Tula region state institution Health Tula regio
Tula, 300053, Russia
Hospital de la Santa Creu i Sant Pau
Barcelona, 08041, Spain
Hospital Universitario Reina Sofia
Córdoba, 14004, Spain
Local Institution - 314
Córdoba, 14004, Spain
Hospital Universitario Infanta Leonor
Madrid, 28031, Spain
Hospital Universitario Fundacion Jimenez Diaz
Madrid, 28040, Spain
Hospital Costa del Sol
Marbella, 29603, Spain
Local Institution - 315
Marbella, 29603, Spain
Hospital Morales Meseguer
Murcia, 30008, Spain
Local Institution - 318
Murcia, 30008, Spain
Hospital Universitario de Salamanca
Salamanca, 37007, Spain
Local Institution - 311
Salamanca, 37007, Spain
Hospital Universitario Virgen Del Rocio
Seville, 41013, Spain
Cukurova University Medical Faculty Balcali Hospital
Adana, 01330, Turkey (Türkiye)
Hacettepe Universitesi
Ankara, 06100, Turkey (Türkiye)
Pamukkale University Medical Faculty
Denizli, 20070, Turkey (Türkiye)
Gaziantep University
Gaziantep, 27310, Turkey (Türkiye)
Marmara University
Istanbul, 34840, Turkey (Türkiye)
Dokuz Eylul University Izmir
Izmir, 35340, Turkey (Türkiye)
19 Mayis Medical Faculty - Samsun
Samsun, 55139, Turkey (Türkiye)
Kocaeli Derince Training and Research Hospital
Umuttepe Kocaeli, 41380, Turkey (Türkiye)
Eastbourne District General Hospital
Eastbourne, BN21 2UD, United Kingdom
Royal Liverpool University Hospital, Prescot Street
Liverpool, L7 8XP, United Kingdom
Barts Cancer Institute, Queen Mary University of London, Charterhouse Square
London, EC1M 6BQ, United Kingdom
Southend University Hospital NHS Foundation Trust, Prittlewell Chase
Westcliff-on-Sea, SS0 0RY, United Kingdom
Related Publications (2)
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: 30184451BACKGROUNDLeonard 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.
PMID: 30897038RESULT
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Bristol-Myers Squibb Study Director
- Organization
- Bristol-Myers Squibb
Study Officials
- STUDY DIRECTOR
Bristol-Myers Squibb
Bristol-Myers Squibb
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 5, 2013
First Posted
September 10, 2013
Study Start
November 21, 2013
Primary Completion
June 22, 2018
Study Completion
January 26, 2022
Last Updated
February 22, 2023
Results First Posted
August 13, 2019
Record last verified: 2023-01