Lymphoma, Non-HodgkinPhase 3AUGMENTNCT01938001
Rituximab Plus Lenalidomide for Patients With Relapsed / Refractory Indolent Non-Hodgkin's Lymphoma (Follicular Lymphoma and Marginal Zone Lymphoma)
A Phase 3 study testing Rituximab and Lenalidomide in people with Lymphoma, Non-Hodgkin, run by Celgene at 160 sites in 17 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphoma, Non-Hodgkin
- What is being tested?
- Rituximab and Lenalidomide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 358 participants
- Where
- 160 sitesin 17 countries
- Study dates
- 21 Nov 2013to 26 Jan 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
160 sites in 17 countries.
160 sites in 17 countries
United States35 sites
University of New Mexico
Albuquerque, New Mexico, 87102
Arlington Cancer Center
Arlington, Texas, 76012
Oncology Hematology Care Sarah Cannon Research
Cincinnati, Ohio, 45242
Iowa Oncology Research Association
Des Moines, Iowa, 50309
Southwest Cancer Care Medical Group
Escondido, California, 92025
Arizona Center for Cancer Care
Glendale, Arizona, 85306
Marin Oncology Associates
Greenbrae, California, 94904-2007
St Francis Hospital
Greenville, South Carolina, 29607
The Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, 07601
NH Oncology - Hematology, PA
Hooksett, New Hampshire, 03106
MD Anderson Cancer Center
Houston, Texas, 77030
Wilshire Oncology Medical Group, Inc
La Verne, California, 91750
LRG Healthcare Oncology Clinic
Laconia, Indiana, 03246
University of Louisville, J.G. Brown Cancer Center
Louisville, Kentucky, 40202
Mitchell Cancer Center, University of South Alabama
Mobile, Alabama, 36604
Hematology-Oncology Associates of Northern NJ
Morristown, New Jersey, 07962
Sarah Cannon Research Inst
Nashville, Tennessee, 37203
Weill Cornell Medical College
New York, New York, 10065
North County Hematology Oncology (NCHO) - TRM, LLC.
Oceanside, California, 92056
Hematology-Oncology Medical Group of Orange County, Inc.
Orange, California, 92868
Illinois Cancer Care, P.C.
Peoria, Illinois, 61615
Local Institution - 028
Portland, Oregon, 97213
Providence Portland Medical Center
Portland, Oregon, 97213
Mayo Clinic
Rochester, Minnesota, 55905
UC Davis Medical Center
Sacramento, California, 95817
Coborn Cancer Center at the St. Cloud Hospital
Saint Cloud, Minnesota, 56303
Central Coast Medical Oncology Corporation
Santa Maria, California, 93454
Providence Cancer Institute
Southfield, Michigan, 48075
Cancer Center of Central Connecticut
Southington, Connecticut, 06489
Spartanburg Regional Healthcare System - Gibbs Cancer Center & Research Institute
Spartanburg, South Carolina, 29303
Florida Cancer Specialists North Region Sarah Cannon Research
St. Petersburg, Florida, 33705
SUNY Upstate Medical University
Syracuse, New York, 13210
Northwest Medical Specialties PLLC
Tacoma, Washington, 98405
Wellness Hematology Oncology
West Hills, California, 92056
Wake Forest Baptist Health
Winston-Salem, North Carolina, 27157
China19 sites
Peking University People's Hospital
Beijing, 100044
307 Hospital of PLA
Beijing, 100071
Peking Union Medical College Hospital
Beijing, 100730
Beijing Cancer Hospital
Beijing, PR, 100142
The Third Xiangya hospital of central south university
Changsha, 410013
West China Hospital of Sichuan University
Chengdu, 610041
Fujian Medical University Union Hospital
Fuzhou, 350001
Sun Yat-sen University Cancer Center
Guangzhou, 510060
Guangdong General Hospital
Guangzhou, 510080
Local Institution - 600
Guangzhou, 510080
The First Affiliated Hospital of Medical School of Zhejiang University
Hangzhou, 310003
Local Institution - 604
Hangzhou, 310006
Jiangsu Province Hospital The First Hospital affiliated with Nanjing Medical University
Nanjing, 210029
Cancer Hospital, Fudan University
Shanghai, 200032
Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Shanghai
The First Affiliated Hospital of Soochow University
Suzhou, 215006
Chinese Academy of Medical Sciences & Peking Union Medical College
Tianjin, 300020
Tianjin Medical University Cancer Institute and Hospital
Tianjin, 300060
Xijing Hospital
Xi'an, 710032
Italy16 sites
Centro di Riferimento Oncologico - IRCCS
Aviano (PN), 33081
U.O.C. Ematologia
Barletta, 76121
A.O.U. di Bologna Policlinico S.Orsola-Malpighi
Bologna, 40138
Azienda Ospedaliera di Rilievo Nazionale e di Alta Specializzazione Garibaldi - Nesima
Catania, 95124
Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori (I.R.S.T.)
Meldola, 47014
Istituto Europeo di Oncologia - IEO
Milan, 20141
Ospedale Niguarda Ca Granda
Milan, 20162
IRCCS- Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione "G. Pascale"
Naples, 80131
Az. Osp. Vincenzo Cervello
Palermo, 90146
Casa di Cura La Maddalena
Palermo, 90146
Azienda Ospedaliero-Universitaria di Parma
Parma, 43100
Ospedale di Ravenna
Ravenna, 48121
Azienda Ospedaliera Bianchi-Melacrino-Morelli
Reggio Calabria, 89100
Ospedale degli Infermi di Rimini
Rimini, 47900
Azienda Ospedaliera S. Andrea - Università La Sapienza
Roma, 00189
Local Institution - 340
Roma, 00189
Japan13 sites
National Cancer Center Hospital
Chūōku, 104-0045
Chugoku Central Hospital
Hiroshima, 7200001
National Cancer Center Hospital East
Kashiwa, 277-8577
Kobe City Medical Center General Hospital
Kobe, 650-0047
The Cancer Institute Hospital of Japanese Foundation For Cancer Research
Kōtoku, 135-8550
Local Institution - 700
Kōtoku, 1350063
University Hospital, Kyoto Prefectural University of Medicine
Kyoto, 602-8566
Local Institution - 709
Minato-ku, Tokyo, 105-8470
Toranomon Hospital
Minatoku, 105-8470
Local Institution - 708
Nagasaki, Nagasaki, 852-8511
The Japanese Red Cross Nagasaki Genbaku Hospital
Nagasaki, 852-8511
Nagoya Medical Center,Division of Hematology/Oncology
Nagoya, 460-0001
National University Corporation Tohoku University, Tohoku University Hospital
Sendai, 980-8574
Spain12 sites
Hospital de la Santa Creu i Sant Pau
Barcelona, 08041
Hospital Universitario Reina Sofia
Córdoba, 14004
Local Institution - 314
Córdoba, 14004
Hospital Universitario Infanta Leonor
Madrid, 28031
Hospital Universitario Fundacion Jimenez Diaz
Madrid, 28040
Hospital Costa del Sol
Marbella, 29603
Local Institution - 315
Marbella, 29603
Hospital Morales Meseguer
Murcia, 30008
Local Institution - 318
Murcia, 30008
Hospital Universitario de Salamanca
Salamanca, 37007
Local Institution - 311
Salamanca, 37007
Hospital Universitario Virgen Del Rocio
Seville, 41013
Brazil10 sites
Fundacao Pio XII - Hospital de Cancer de Barretos
Barretos, São Paulo, 14784-400
Hospital Dr. Amaral Carvalho/ Hospital Amaral Carvalho Jaú
Jau/SP, São Paulo, 17210-080
Associacao Hospitalar Moinhos de Vento Hospital Moinhos de Vento
Porto Alegre, Rio Grande do Sul, 90035-001
Hospital de Clínicas de Porto Alegre
Porto Alegre, Rio Grande do Sul, 90035-903
Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da PUCRS
Porto Alegre, Rio Grande do Sul, 90610-000
Associacao Educudora Sao Carlos AESC Hospital Giovanni Battista HGB Hospital Mae de Deus Center
Porto Alegre, Rio Grande do Sul, 90740-340
MS INCA HC I Hospital do Cancer I
Rio de Janeiro, 20231-130
Sociedade Beneficente de Senhoras Hospital Sirio Libanes
São Paulo, 01308 050
Real e Benemerita Associacao Portuguesa de Beneficencia
São Paulo, 01321-001
Fundação Antonio Prudente - AC Camargo Câncer center
São Paulo, 01509-900
Turkey (Türkiye)8 sites
Cukurova University Medical Faculty Balcali Hospital
Adana, 01330
Hacettepe Universitesi
Ankara, 06100
Pamukkale University Medical Faculty
Denizli, 20070
Gaziantep University
Gaziantep, 27310
Marmara University
Istanbul, 34840
Dokuz Eylul University Izmir
Izmir, 35340
19 Mayis Medical Faculty - Samsun
Samsun, 55139
Kocaeli Derince Training and Research Hospital
Umuttepe Kocaeli, 41380
France7 sites
CHU d'Angers
Angers, 49033
Centre Hospitalier Universitaire d'Avicennes
Bobigny, 93009
CHRU de Brest - Hopital Morvan
Brest, 29609
Hopital Saint-Louis
Paris, 75010
CH Perpignan - Hopital Saint-Jean
Perpignan, 66046
CHU de Poitiers
Poitiers, 86021
Centre Hospitalier de Valence
Valence, 26953
Czechia6 sites
Interni hematoonkologicka klinika
Brno, 625 00
Fakultni nemocnice Hradec Kralove, IV.interni hematologicka klinika
Hradec Králové, 500 05
Fakultni Nemocnice Ostrava, Klinika hematoonkologie,
Ostrava, 70852
Fakultni nemocnice Kralovske Vinohrady, Interni hematologicka klinika
Prague, 100 34
Local Institution - 534
Prague, 128 08
Vseobecna Fakultni Nemocnice v Praze
Prague, 128 08
Germany6 sites
Charite - Universitaetsmedizin Berlin Charité - Campus Benjamin Franklin
Berlin, 12203
Charite - Universitaetsmedizin Berlin Campus Virchow Klinikum
Berlin, 13353
Krankenhaus Nordwest
Frankfurt, 60488
Onkologische Schwerpunktpraxis Leer - Emden
Leer, 26789
Kliniken Maria Hilf GmbH
Mönchengladbach, 41063
Klinkum der Stadt Villingen-Schwenningen GmbH
Villingen-Schwenningen, 78052
Russia6 sites
Krasnoyarsk Regional Clinical Hospital
Krasnoyarsk, 660022
Russian Academy of Medical Sciences Institution
Moscow, 115478
Moscow State Medical Institution Municipal Clinical Hospital n.a. S.P. Botkin
Moscow, 125101
St. Petersburg Pavlov State Medical University
Saint Petersburg, 197022
Federal Centre of Heart, Blood and Endocrinology of Rosmed technlologies V.A. Almazov
Saint Petersburg, 197341
The Ministry of Health and Social Development of the Tula region state institution Health Tula regio
Tula, 300053
Belgium5 sites
AZ St-Jan Brugge Oostende AV
Bruges, 8000
Local Institution - 371
Ghent, 9000
UZ Gent
Ghent, 9000
AZ Groeninge
Kortrijk, 8500
CHU Mont -Godinne
Yvoir, 5530
Poland5 sites
Malopolskie Centrum Medyczne S.C.
Krakow, 30-510
Instytut Hematologii i Transfuzjologii w Warszawie
Warsaw, 02-776
Local Institution - 514
Warsaw, 02-776
Centrum Onkologii, Instytut im. Marii Sklodowskiej-Curie
Warsaw, 02-781
Local Institution - 513
Warsaw, 02-781
Portugal4 sites
Instituto Portugues de Oncologia de Lisboa, Francisco Gentil
Lisbon, 1099-023
Local Institution - 330
Lisbon, 1099-023
Instituto Portugues de Oncologia do Porto, Francisco Gentil
Porto, 4200-072
Local Institution - 331
Porto, 4200-072
United Kingdom4 sites
Eastbourne District General Hospital
Eastbourne, BN21 2UD
Royal Liverpool University Hospital, Prescot Street
Liverpool, L7 8XP
Barts Cancer Institute, Queen Mary University of London, Charterhouse Square
London, EC1M 6BQ
Southend University Hospital NHS Foundation Trust, Prittlewell Chase
Westcliff-on-Sea, SS0 0RY
Israel3 sites
Soroka University Medical Center
Beersheba, 84101
Hadassah University Hospital
Jerusalem, 91120
Tel-Aviv Sourasky Medical Center
Tel Aviv, 64239
About this study
Official title: 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
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.
Read the 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
- Being tested
- Rituximab, Lenalidomide, Placebo
- Keywords
- Non-Hodgkins Follicular lymphoma, Non-Hodgkins Marginal zone lymphoma, treatment for follicular lymphoma, treatment for Marginal zone lymphoma
- Medical subject headings
- Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabDrug
Also called Rituxan
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
LenalidomideDrug
Also called CC-5013, Revlimid
Lenalidomide 20mg by mouth (PO) daily on Days 1 to 21 every 28 days up to 12 cycles
PlaceboDrug
Placebo (identical matched capsule) PO daily on Days 1 to 21 every 28 days
| Study group | Role | What they receive |
|---|---|---|
| Rituximab and Lenalidomide | Experimental | 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. Receives: Drug: Rituximab; Drug: Lenalidomide |
| Rituximab and Placebo | Active comparator | 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. Receives: Drug: Rituximab; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
DCCR was defined as the percentage of participants with a best response of complete response (CR) that lasted no less than one year (≥ 48 weeks) during the study prior to administration of new anti-lymphoma therapy. A CR is defined as a complete disappearance of any disease-related symptoms and normalization of biochemical abnormalities.
Measured: 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)
Overall survival was defined as the time from randomization to death from any cause. Overall survival was censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for participants who were lost to follow-up before death was documented.
Measured: 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
Percentage of participants with an objective response is defined as having a response of at least a PR during the study without administration of new anti-lymphoma therapy. A complete response = a complete disappearance of all detectable clinical and radiographic evidence of disease, disappearance of any disease-related symptoms, and normalization of biochemical abnormalities; a partial response (PR) = 50% decrease in SPD of the 6 largest dominant nodes or nodal masses. No increase in the size of other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD.
Measured: 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
Percentage of participants with a best response of at CR during the study without administration of new anti-lymphoma therapy. A CR = Complete disappearance of all detectable clinical and radiographic evidence of disease, disappearance of any disease-related symptoms, and normalization of biochemical abnormalities.
Measured: 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
Duration of response (DOR) was defined as the time from initial response (at least PR) until documented progressive disease (PD) or death. Participants who had not progressed at the time of analysis were censored at the last assessment date that the participant was known to be progression free. Participants who received a new treatment without documented progression were censored at the last assessment date that the participants was known to be progression free.
Measured: 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).
Kaplan-Meier Estimate of Duration of Complete Response (DOCR) as Assessed by the IRC According to the 2007 IWGRC
DOCR was defined as the time from initial CR until documented PD or death. Participants who had not progressed at the time of analysis were censored at the last assessment date that the participant was known to be progression free. Participants who received a new treatment without documented progression were censored at the last assessment date that the participants was known to be progression free.
Measured: 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).
Kaplan Meier Estimate of Event Free Survival as Assessed by the IRC According to the 2007 IWGRC
Event-free survival (EFS) was defined as the time from date of randomization to date of first documented progression, relapse, institution of new anti-lymphoma treatment (chemotherapy, radiotherapy or immunotherapy) or death from any cause. Responding participants and those who were lost to follow up were censored at their last tumor assessment date.
Measured: From date of randomization 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).
Kaplan Meier Estimate of Time to Next Anti-Lymphoma Treatment (TTNLT)
Time to next anti-lymphoma treatment (TTNLT) was defined as the time from date of randomization to date of first documented administration of a new anti-lymphoma treatment (including chemotherapy, radiotherapy, radioimmunotherapy or immunotherapy). The time to the next anti-lymphoma treatment was of special interest to the study.
Measured: From date of randomization to date of first documented administration of a new anti-lymphoma treatment (Average of 55.71 months and a maximum up to 95.2 months)
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
TEAEs include AEs that started or worsened between the date of the first dose and 28 days after the date of the last dose. A serious adverse event (SAE) is any: • Death; • Life-threatening event; • Any inpatient hospitalization or prolongation of existing hospitalization; • Persistent or significant disability or incapacity; • Congenital anomaly or birth defect; • Any other important medical event. The investigator determined the relationship of an AE to study drug based on the timing of the AE relative to drug administration and whether or not other drugs, therapeutic interventions, or underlying conditions could provide a sufficient explanation for the event. The severity of an AE was evaluated by the investigator according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (Version 4.03) where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Death
Measured: From first dose to 28 days post last dose (Average of 55.71 months and a maximum up to 95.2 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2013 (estimated)
- Study start21 Nov 2013
- Primary completion22 Jun 2018
- Study completion26 Jan 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Lymphoma, Non-HodgkinStudies of the same condition, open and under way.
- More trials run by CelgeneThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 358 participants (actual)
Sponsor and investigators
- Lead sponsor
- Celgene
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01938001
- Sponsor's protocol ID
- CC-5013-NHL-007
- Acronym
- AUGMENT
- Status last verified
- Jan 2023
- First submitted
- 5 Sep 2013
- Last updated
- 22 Feb 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 30184451Leonard 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.
PubMed 30897038Leonard JP, Trneny M, Zhang H, Nowakowski GS, Izutsu K, Fowler N, Thieblemont C, Zinzani PL, Gkasiamis A, Ahn JR, Gribben JG; AUGMENT Trial Investigators. Lenalidomide Plus Rituximab for Relapsed/Refractory Indolent Non-Hodgkin Lymphoma: 5-Year Follow-Up and Subgroup Analyses From the Phase III AUGMENT Trial. J Clin Oncol. 2026 Jun;44(16):1483-1489. doi: 10.1200/JCO-25-01770. Epub 2026 Apr 16.
PubMed 41990300
Study at a glance
From the registry record, last updated by the sponsor on 22 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01938001
- Acronym / sponsor ID
- AUGMENT / CC-5013-NHL-007
- Conditions
- Lymphoma, Non-Hodgkin
- Keywords
- Non-Hodgkins Follicular lymphoma, Non-Hodgkins Marginal zone lymphoma, treatment for follicular lymphoma, treatment for Marginal zone lymphoma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 358 participants (actual)
- Lead sponsor
- CelgeneIndustry (pharma, biotech, devices)
- Study start
- 21 Nov 2013 (actual)
- Primary completion
- 22 Jun 2018 (actual)
- Study completion
- 26 Jan 2022 (actual)
- First posted
- 10 Sep 2013 (estimated)
- Results
- Posted 13 Aug 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rituximab and Lenalidomide | Experimental | Drug: Rituximab, Drug: LenalidomideParticipants 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 comparator | Drug: Rituximab, Drug: PlaceboParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (17 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RituximabAlso: RituxanRituximab 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 | Drug | Rituximab and Lenalidomide, Rituximab and Placebo |
| LenalidomideAlso: CC-5013, RevlimidLenalidomide 20mg by mouth (PO) daily on Days 1 to 21 every 28 days up to 12 cycles | Drug | Rituximab and Lenalidomide |
| PlaceboPlacebo (identical matched capsule) PO daily on Days 1 to 21 every 28 days | Drug | Rituximab and Placebo |
Primary outcome
Kaplan Meier Estimate of Progression Free Survival Assessed by the Independent Review Committee (IRC) According to the 2007 International Working Group Response Criteria (IWGRC)
Time frame: 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).
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.
9 secondary outcomes
Durable Complete Response Rate (DCCR) as Assessed by the IRC According to the 2007 IWGRC
Time frame: 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)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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).
Kaplan-Meier Estimate of Duration of Complete Response (DOCR) as Assessed by the IRC According to the 2007 IWGRC
Time frame: 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).
Kaplan Meier Estimate of Event Free Survival as Assessed by the IRC According to the 2007 IWGRC
Time frame: From date of randomization 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).
Kaplan Meier Estimate of Time to Next Anti-Lymphoma Treatment (TTNLT)
Time frame: From date of randomization to date of first documented administration of a new anti-lymphoma treatment (Average of 55.71 months and a maximum up to 95.2 months)
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Time frame: From first dose to 28 days post last dose (Average of 55.71 months and a maximum up to 95.2 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Feb 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 30184451Morschhauser 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.
- Results publication: PubMed 30897038Leonard 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.
- Derived from this study: PubMed 41990300Leonard JP, Trneny M, Zhang H, Nowakowski GS, Izutsu K, Fowler N, Thieblemont C, Zinzani PL, Gkasiamis A, Ahn JR, Gribben JG; AUGMENT Trial Investigators. Lenalidomide Plus Rituximab for Relapsed/Refractory Indolent Non-Hodgkin Lymphoma: 5-Year Follow-Up and Subgroup Analyses From the Phase III AUGMENT Trial. J Clin Oncol. 2026 Jun;44(16):1483-1489. doi: 10.1200/JCO-25-01770. Epub 2026 Apr 16.
- BMS Clinical Trial InformationLink provided by the sponsor.
- BMS Clinical Trial Patient RecruitingLink provided by the sponsor.
- FDA Safety Alerts and RecallsLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
160 sites in 17 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Rituximab and Lenalidomide in people with Lymphoma, Non-Hodgkin, run by Celgene at 160 sites in 17 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 160 sites in United States, China, Italy, Japan, Spain and 12 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Kaplan Meier Estimate of Progression Free Survival Assessed by the Independent Review Committee (IRC) According to the 2007 International Working Group Response Criteria (IWGRC) (time frame: 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).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01938001, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Feb 2023.