A Study of the Bruton's Tyrosine Kinase Inhibitor Ibrutinib Given in Combination With Bendamustine and Rituximab in Patients With Newly Diagnosed Mantle Cell Lymphoma
A Randomized, Double-blind, Placebo-controlled Phase 3 Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor, PCI-32765 (Ibrutinib), in Combination With Bendamustine and Rituximab (BR) in Subjects With Newly Diagnosed Mantle Cell Lymphoma
4 other identifiers
interventional
523
28 countries
201
Brief Summary
The purpose of this study is to evaluate the efficacy and safety of ibrutinib given in combination with bendamustine and rituximab in patients 65 years of age or older with newly diagnosed mantle cell lymphoma.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started May 2013
Longer than P75 for phase_3
201 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
January 24, 2013
CompletedFirst Posted
Study publicly available on registry
January 28, 2013
CompletedStudy Start
First participant enrolled
May 16, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 30, 2021
CompletedResults Posted
Study results publicly available
July 26, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
June 24, 2024
CompletedJuly 8, 2025
June 1, 2025
8.1 years
January 24, 2013
June 30, 2022
June 18, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression-free Survival (PFS)
Progression-free survival (PFS) was defined as the interval between the date of randomization to the date of disease progression (PD) or relapse from complete response (CR) or death, whichever was first reported. Disease assessments were based on the 2007 Revised Response Criteria for Malignant Lymphoma. PD was defined as any new lesion or increase by 50 percent (%) of previously involved sites from nadir (PD criteria: Appearance of new nodal lesion 1.5 centimeters \[cm\] in any axis, 50% increase in sum of product of diameters \[SPD\] of greater than \[\>\] 1 node or 50% increase in longest diameter of previously identified node 1 cm in short axis).
Up to 97 months
Secondary Outcomes (15)
Overall Survival
From randomization (Day -3) up to 121 months
Complete Response Rate
Up to 97 months
Time-to-Next Treatment
Up to 97 months
Percentage of Participants With Overall Response
Up to 97 months
Minimal Residual Disease (MRD)-Negative Response Rate
Up to 97 months
- +10 more secondary outcomes
Study Arms (2)
Treatment Arm A
PLACEBO COMPARATORTreatment Arm B
EXPERIMENTALInterventions
90 mg/m2 administered intravenously on Days 1-2, Cycles 1-6
375 mg/m2 administered intravenously on Day 1, Cycles 1-6; if complete response or partial response is achieved, 375 mg/m2 is administered on Day 1 of every second cycle for a maximum of 12 additional doses
560 mg (4 x 140 mg capsules) administered orally once daily continuously starting on Day 1, Cycle 1 until disease progression, or unacceptable toxicity, or study end
4 capsules administered orally once daily continuously starting on Day 1, Cycle 1 until disease progression, or unacceptable toxicity, or the final analysis of progression-free survival
Eligibility Criteria
You may qualify if:
- Diagnosis of mantle cell lymphoma (MCL) reviewed and approved by central laboratory: diagnosis must include morphology and expression of either cyclin D1 in association with other relevant markers (eg, CD19, CD20, PAX5 and CD5) or evidence of t(11;14) as assessed by cytogenetics, fluorescent in situ hybridization (FISH), or polymerase chain reaction (PCR)
- Clinical Stage II, III, or IV by Ann Arbor Classification
- At least 1 measurable site of disease according to Revised Response Criteria for Malignant Lymphoma
- No prior therapies for MCL
- Eastern Cooperative Oncology Group (ECOG) performance status grade 0 or 1
- Hematology and biochemical laboratory values within protocol-defined limits
- Agrees to protocol-defined use of effective contraception
- Negative blood or urine pregnancy test at screening
You may not qualify if:
- Major surgery within 4 weeks of random assignment
- Known central nervous system lymphoma
- Diagnosed or treated for malignancy other than MCL, except: malignancy treated with curative intent and with no known active disease present for \>=3 years before random assignment; adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease; adequately treated cervical carcinoma in situ without evidence of disease
- Patients for whom the goal of therapy is tumor debulking prior to stem cell transplant
- History of stroke or intracranial hemorrhage within 6 months prior to random assignment
- Requires anticoagulation with warfarin or equivalent vitamin K antagonists
- Requires treatment with strong CYP3A inhibitors
- Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification
- Vaccinated with live, attenuated vaccines within 4 weeks of random assignment
- Known history of human immunodeficiency virus (HIV) or active hepatitis C virus or active hepatitis B virus infection or any uncontrolled active systemic infection requiring intravenous antibiotics
- Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the patient's safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Janssen Research & Development, LLClead
- Pharmacyclics LLC.collaborator
Study Sites (201)
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Tucson, Arizona, United States
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Burbank, California, United States
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La Jolla, California, United States
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Stanford, California, United States
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Denver, Colorado, United States
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New Haven, Connecticut, United States
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Stamford, Connecticut, United States
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Chicago, Illinois, United States
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Maywood, Illinois, United States
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Niles, Illinois, United States
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Springfield, Illinois, United States
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Goshen, Indiana, United States
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Iowa City, Iowa, United States
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Sioux City, Iowa, United States
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Topeka, Kansas, United States
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Westwood, Kansas, United States
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Lexington, Kentucky, United States
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Louisville, Kentucky, United States
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Metairie, Louisiana, United States
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Ann Arbor, Michigan, United States
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Detroit, Michigan, United States
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Jefferson City, Missouri, United States
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Lincoln, Nebraska, United States
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Hackensack, New Jersey, United States
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New Brunswick, New Jersey, United States
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Albuquerque, New Mexico, United States
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Albany, New York, United States
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Hawthorne, New York, United States
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New York, New York, United States
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Durham, North Carolina, United States
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Greenville, North Carolina, United States
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Bismarck, North Dakota, United States
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Fargo, North Dakota, United States
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Eugene, Oregon, United States
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Portland, Oregon, United States
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Philadelphia, Pennsylvania, United States
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Greenville, South Carolina, United States
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Watertown, South Dakota, United States
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Nashville, Tennessee, United States
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Houston, Texas, United States
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San Antonio, Texas, United States
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Burlington, Vermont, United States
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Spokane, Washington, United States
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Vancouver, Washington, United States
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Buenos Aires, Argentina
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Córdoba, Argentina
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La Capital, Argentina
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Paraná, Argentina
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Adelaide, Australia
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Auchenflower, Australia
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Box Hill, Australia
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Concord, Australia
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Douglas, Australia
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Gosford, Australia
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Hobart, Australia
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Prahran, Australia
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Antwerp, Belgium
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Bruges, Belgium
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Brussels, Belgium
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Ghent, Belgium
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Leuven, Belgium
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Wilrijk, Belgium
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Yvoir, Belgium
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Barretos, Brazil
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Goiânia, Brazil
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Porto Alegre, Brazil
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Ribeirão Preto, Brazil
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Rio de Janeiro, Brazil
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São Paulo, Brazil
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Edmonton, Alberta, Canada
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Vancouver, British Columbia, Canada
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Hamilton, Ontario, Canada
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Ottawa, Ontario, Canada
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Montreal, Quebec, Canada
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Beijing, China
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Chengdu, China
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Guangzhou, China
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Hangzhou, China
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Shanghai, China
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Tianjin, China
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Brno, Czechia
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Hradec Králové, Czechia
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Prague, Czechia
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Créteil, France
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F-75 730 Paris Cedex 15, France
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Grenoble, France
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Nantes, France
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Paris, France
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Pessac, France
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Tours, France
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Berlin, Germany
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Heidelberg, Germany
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Jena, Germany
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Mainz, Germany
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München, Germany
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TÿBINGEN, Germany
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Ulm, Germany
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Villingen-Schwenningen, Germany
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Athens, Greece
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Athens Attica, Greece
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Thessalonikis, Greece
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Budapest, Hungary
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Debrecen, Hungary
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Kaposvár, Hungary
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Pécs, Hungary
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Szeged, Hungary
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Dublin, Ireland
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Galway, Ireland
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Afula, Israel
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Beersheba, Israel
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Haifa, Israel
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Jerusalem, Israel
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Nahariya, Israel
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Petah Tikva, Israel
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Ramat Gan, Israel
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Tel Aviv, Israel
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Ẕerifin, Israel
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Fukuoka, Japan
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Hiroshima, Japan
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Kyoto, Japan
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Nagoya, Japan
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Osaka, Japan
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Sapporo, Japan
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Sendai, Japan
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Suita, Japan
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Tokyo, Japan
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Monterrey, Mexico
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Oaxaca City, Mexico
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Amsterdam-Zuidoost, Netherlands
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Dordrecht, Netherlands
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Groningen, Netherlands
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Leiden, Netherlands
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Rotterdam, Netherlands
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Utrecht, Netherlands
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Bydgoszcz, Poland
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Krakow, Poland
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Olsztyn, Poland
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Warsaw, Poland
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Wroclaw, Poland
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San Juan, Puerto Rico
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Chelyabinsk, Russia
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Krasnodar, Russia
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Moscow, Russia
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Nizhny Novgorod, Russia
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Novosibirsk, Russia
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Petrozavodsk, Russia
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Rostov-on-Don, Russia
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Ryazan, Russia
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Saint Petersburg, Russia
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Sochi, Russia
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St.Petersurg, Russia
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Syktyvkar, Russia
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Volgograd, Russia
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Yekaterinburg, Russia
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Banská Bystrica, Slovakia
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Bratislava, Slovakia
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Košice, Slovakia
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Martin, Slovakia
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Prešov, Slovakia
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Gyeonggi-do, South Korea
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Jeollanam-do, South Korea
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Seoul, South Korea
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Barcelona, Spain
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Madrid, Spain
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Oviedo, Spain
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Palma de Mallorca, Spain
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Salamanca, Spain
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Santiago de Compostela, Spain
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Linköping, Sweden
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Lund, Sweden
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Stockholm, Sweden
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Umeaa, Sweden
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Uppsala, Sweden
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Changhua, Taiwan
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Kaohsiung County, Taiwan
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Taichung, Taiwan
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Tainan, Taiwan
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Taipei, Taiwan
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Taoyuan District, Taiwan
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Adana, Turkey (Türkiye)
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Ankara, Turkey (Türkiye)
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Diyarbakır, Turkey (Türkiye)
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Istanbul, Turkey (Türkiye)
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Izmir, Turkey (Türkiye)
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Kayseri, Turkey (Türkiye)
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Mersin, Turkey (Türkiye)
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Cherkassy, Ukraine
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Donetsk, Ukraine
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Khmelnitskiy, Ukraine
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Kiev, Ukraine
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Lviv, Ukraine
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Canterbury, United Kingdom
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Glasgow, United Kingdom
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Leeds, United Kingdom
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Leicester, United Kingdom
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Liverpool, United Kingdom
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London, United Kingdom
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Manchester, United Kingdom
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Plymouth, United Kingdom
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Southampton, United Kingdom
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Sutton, United Kingdom
Related Publications (1)
Wang ML, Jurczak W, Jerkeman M, Trotman J, Zinzani PL, Belada D, Boccomini C, Flinn IW, Giri P, Goy A, Hamlin PA, Hermine O, Hernandez-Rivas JA, Hong X, Kim SJ, Lewis D, Mishima Y, Ozcan M, Perini GF, Pocock C, Song Y, Spurgeon SE, Storring JM, Walewski J, Zhu J, Qin R, Henninger T, Deshpande S, Howes A, Le Gouill S, Dreyling M; SHINE Investigators. Ibrutinib plus Bendamustine and Rituximab in Untreated Mantle-Cell Lymphoma. N Engl J Med. 2022 Jun 30;386(26):2482-2494. doi: 10.1056/NEJMoa2201817. Epub 2022 Jun 3.
PMID: 35657079DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- EXECUTIVE MEDICAL DIRECTOR
- Organization
- Janssen Research & Development, LLC
Study Officials
- STUDY DIRECTOR
Janssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 24, 2013
First Posted
January 28, 2013
Study Start
May 16, 2013
Primary Completion
June 30, 2021
Study Completion
June 24, 2024
Last Updated
July 8, 2025
Results First Posted
July 26, 2022
Record last verified: 2025-06