Study of Ibrutinib Combined With Venetoclax in Subjects With Mantle Cell Lymphoma (MCL)
NCT ID: NCT03112174
Last Updated: 2025-07-22
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE3
366 participants
INTERVENTIONAL
2017-06-19
2024-06-27
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
TRIPLE
Study Groups
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Safety Run-in
Participants with a low or high risk of TLS enroll into the open-label Safety Run-in Period to receive concurrent ibrutinib at 560 mg once daily and venetoclax starting at 20 mg, and gradually ramp up to a target dose of 400 mg once daily over a 5-week period.
Ibrutinib
Administered orally once daily
Venetoclax
Administered orally once daily
Randomization Phase: Ibrutinb + Venetoclax
Participants randomized to ibrutinib and venetoclax for approximately 104 weeks, followed by ibrutinib monotherapy until disease progression (PD), unacceptable toxicity or withdrawal of consent. Venetoclax is discontinued after 104 weeks of treatment, regardless of response assessment.
Ibrutinib
Administered orally once daily
Venetoclax
Administered orally once daily
Randomization Phase: Ibrutinib + Placebo
Participants randomized to ibrutinib and placebo for approximately 104 weeks, followed by ibrutinib monotherapy until PD, unacceptable toxicity or withdrawal of consent. Placebo is discontinued after 104 weeks of treatment, regardless of response assessment.
Ibrutinib
Administered orally once daily
Placebo Oral tablet to match Venetoclax
Administered orally once daily
Treatment-naive Open-label Arm
Participants are treated with ibrutinib 560 mg and venetoclax 400 mg, administered using the 5-week ramp-up schedule.
Ibrutinib
Administered orally once daily
Venetoclax
Administered orally once daily
Interventions
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Ibrutinib
Administered orally once daily
Venetoclax
Administered orally once daily
Placebo Oral tablet to match Venetoclax
Administered orally once daily
Eligibility Criteria
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Inclusion Criteria
* At least 1 measurable site of disease on cross-sectional imaging (CT).
* At least 1, but no more than 5, prior treatment regimens for MCL.
* Failure to achieve at least partial response (PR) with, or documented disease progression after, the most recent treatment regimen.
* Subjects must have adequate fresh or paraffin embedded tissue.
* Adequate hematologic, hepatic and renal function.
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) of \<= 2.
* Pathologically confirmed treatment-naive MCL (tumor tissue), with documentation of either overexpression of cyclin D1 in association with other relevant markers (eg, CD19, CD20, PAX5, CD5) or evidence of t(11;14), as assessed by cytogenetics, fluorescent in situ hybridization (FISH), or polymerase chain reaction (PCR).
* Men and women ≥18 years of age with a TP53 mutation.
* At least 1 measurable site of disease by CT.
* Must have adequate fresh or paraffin-embedded tissue.
* Eastern Cooperative Oncology Group (ECOG) performance status score 0 to \<= 2.
* Adequate hematologic, hepatic, and renal function.
Exclusion Criteria
* Concurrent enrollment in another therapeutic investigational study or prior therapy with ibrutinib or other BTK inhibitors.
* Prior treatment with venetoclax or other BCL2 inhibitors.
* Anticancer therapy including chemotherapy, radiotherapy, small molecule and investigational agents \<= 21 days prior to receiving the first dose of study drug.
* Treatment with any of the following within 7 days prior to the first dose of study drug: moderate to strong cytochrome P450 3A (CYP3A) inhibitors or strong CYP3A inducers.
Treatment Naïve Arm
* Blastoid variant of MCL
* History or current evidence of CNS lymphoma.
* Concurrent enrollment in another therapeutic investigational study or prior therapy including ibrutinib or other BTK inhibitors.
* Prior treatment with venetoclax or other BCL2 inhibitors.
* Vaccinated with live, attenuated vaccines within 4 weeks of the first dose of study drug.
* Clinically significant infection requiring IV systemic treatment that was completed \<=14 days before the first dose of study drug.
* Any uncontrolled active systemic infection.
* Known bleeding disorders (eg, von Willebrand's disease or hemophilia).
* History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
* History of HIV or active HCV or HBV.
* Major surgery within 4 weeks of the first dose of study drug.
* Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could compromise the participant's safety or put the study outcomes at undue risk.
* Currently active, clinically significant cardiovascular disease; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to randomization.
* Unable to swallow capsules or tablets, or malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction.
* Treatment with any of the following within 7 days prior to the first dose of study drug: Moderate or strong cytochrome P450 3A (CYP3A) inhibitors or moderate or strong CYP3A inducers.
* Known allergy to xanthine oxidase inhibitors and/or rasburicase for subjects with known risk factors (as defined by high tumor burden and/or diminished renal function, as detailed in "Study Design" section above) for TLS.
* Chronic liver disease with hepatic impairment Child-Pugh class B or C.
* Unwilling or unable to participate in all required study evaluations and procedures.
* Known hypersensitivity to the active ingredient or other components of one or more study drugs.
18 Years
ALL
No
Sponsors
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Janssen Research & Development, LLC
INDUSTRY
Pharmacyclics LLC.
INDUSTRY
Responsible Party
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Locations
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The University of Arizona Cancer Centre-North Campus
Tucson, Arizona, United States
City of Hope
Duarte, California, United States
UCLA Department of Medicine-Hematology/Oncology
Los Angeles, California, United States
Orlando Health Inc.
Orlando, Florida, United States
The University of Kansas Cancer Center and Medical Pavilion
Westwood, Kansas, United States
Norton Cancer Institute
Louisville, Kentucky, United States
Barbara Ann Karmanos Cancer institute
Detroit, Michigan, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Stony Brook University
New York, New York, United States
Levine Cancer Institute
Charlotte, North Carolina, United States
Tennessee Oncology
Chattanooga, Tennessee, United States
University of Tennessee medical Center
Knoxville, Tennessee, United States
University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Swedish Cancer Institute
Seattle, Washington, United States
The Canberra Hospital
Canberra, Australian Capital Territory, Australia
Border Medical Oncology Research Unit
Albury, New South Wales, Australia
Icon Cancer Care
Auchenflower, Queensland, Australia
Austin Health
Heidelberg, Victoria, Australia
Peter MacCallum Cancer
Melbourne, Victoria, Australia
St.Vincent's Hospital
Melbourne, Victoria, Australia
Sir Charles Gairdner Hospital
Nedlands, Western Australia, Australia
ZiekenhuisNetwerk Antwerpen (ZNA) Stuivenberg
Antwerp, , Belgium
AZ Sint-Jan Brugge-Oostende AV
Bruges, , Belgium
Institut Jules Bordet
Brussels, , Belgium
CHU UCL Namur asbl- Mont Godinne
Yvoir, , Belgium
Tom Baker Cancer Centre
Calgary, Alberta, Canada
Cross Cancer Institute
Edmonton, Alberta, Canada
BC Cancer-Vancouver Centre
Vancouver, British Columbia, Canada
Queen Elizabeth II Health Science Centre
Halifax, Nova Scotia, Canada
The Ottawa Hospital
Ottawa, Ontario, Canada
Jewish General Hospital
Montreal, Quebec, Canada
FN Brno, Interni hematologicka a onkologicka klinika
Brno, , Czechia
Fakultni Nemocnice (FN) Hradec Kravlove, a.s. IV. Interni hematologicka klinika
Hradec Králové, , Czechia
FN Olomouc
Olomouc, , Czechia
FN Ostrava
Ostrava-Poruba, , Czechia
Fakultni nemocnice Kralovske Vinohrady
Prague, , Czechia
Vseobecna fakultni nemocnice v Praze, l. interni klinika-klinika hematologie
Prague, , Czechia
CHU CAEN-Hôpital de la Côte de Nacre
Caen, Calvados, France
Institut Bergonié
Bordeaux, , France
CHU Clermont Ferrand - Hôpital d'Estaing
Clermont-Ferrand, , France
Institut Paoli Calmettes, Service Hematologie
Marseille, , France
Centre Antoine Lacassagne
Nice, , France
Hôpital Saint-Louis
Paris, , France
Centre Hospitalier Lyon Sud
Pierre-Bénite, , France
CHU de Tours
Tours, , France
Kliniken Ostalb Stauferklinikum Schwab. Gmund
Mutlangen, Baden-Wuttemberg, Germany
Universitaetsklinikum Ulm
Ulm, Baden-Wuttemberg, Germany
Klinikum der Universitaet Muenchen Campus Grosshadern
Munich, Bavaria, Germany
Universitatsklinikum Koln
Kerpen, Koln, Germany
Universitaetsmedizin der Johannes Gutenberg, Langenbeckstrasse 1
Langen, Mainz, Germany
Gemeinschaftpraxis Haematologie und Onkologie
Dresden, Saxony, Germany
Vivantes Klinikum Am Urban
Berlin, , Germany
Charite- Universitatsmedizin Berlin, Campus Benjamin Franklin
Berlin, , Germany
Universitatsklinikum Essen, Klinik fur Hamatologie
Essen, , Germany
Universitatsklinikum des Saarlandes, Klinik fur Innere Medizin I
Homburg/Saar, , Germany
University Hospital of Alexandroupolis
Alexandroupoli, , Greece
251 Air Force General Hospital
Athens, , Greece
General Hospital of Athens Laiko
Athens, , Greece
General Hospital of Athens "Alexandra"
Athens, , Greece
University General Hospital of Ioannina
Ioannina, , Greece
University General Hospital of Larissa
Larissa, , Greece
University Hospital of Patras
Pátrai, , Greece
Orszagos Onkologiai Intezet
Budapest, , Hungary
Semmelweis Egyetem
Budapest, , Hungary
Debreceni Egyetem Klinikai Kozpont, Belgyogyaszati Klinika
Debrecen, , Hungary
Petz Aladar Megyei Oktato Korhaz, II. Belgyogyaszat-Hematologia
Győr, , Hungary
Somogy Megyei Kaposi Mor Oktato Korhaz
Kaposvár, , Hungary
Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ
Szeged, , Hungary
Markusovszky Egyetemi Oktatokorhaz, Haematologiai es Haemoszatazeologiai Osztaly
Szombathely, , Hungary
Azienda Ospedaliera SS Antonio e Biagio e Cesare Arrigo di Alessandria
Alessandria, Alessandria/Piemonte, Italy
Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni XXIII)
Bergamo, Bergamo/Lombardia, Italy
Azienda Ospedaliera Universitaria di Bologna Policlinico Saint Orsola Malpighi
Bologna, Bologna/Emilia-Romagna, Italy
ASST degli Spedali Civili di Brescia
Brescia, Brescia/Lombardia, Italy
Azienda Ospedaliera S. Croce e Carle Cuneo
Cuneo, Cuneo/Piemonte, Italy
Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori
Meldola, Forli-Cesena/Emilia-Rom, Italy
IRCCS Ospedale S. Raffaele di Milano
Milan, Milano/Lombardia, Italy
Asst Grande Ospedale Metropolitano Niguarda
Milan, Milano/Lombardia, Italy
Fondazione IRCCS Policlinico San Matteo
Pavia, Pavia/Lombardia, Italy
Azienda Ospedaliero Universitaria Molinette San Giovanni Battista di Torino
Torino, Torino/Piemonte, Italy
Azienda Ospedaliero-Universitaria Santa Maria della Misericordia
Udine, Udine/Friuli-Venezia Giulia, Italy
Universitair Medisch Centrum Groningen
Groningen, , Netherlands
Spaarne Gasthuis
Hoofddorp, , Netherlands
Leiden University Medical Center
Leiden, , Netherlands
Erasmus MC
Rotterdam, , Netherlands
Franciscus Vlietland
Schiedam, , Netherlands
Szpital Uniwersytecki nr 2 im. dr J. Biziela w Bydgoszcz
Bydgoszcz, , Poland
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich, Oddzial Hematologiczny
Chorzów, , Poland
Malopolskie Centrum Medyczne s c
Krakow, , Poland
Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. Kopernika w Lodzi
Lodz, , Poland
Instytut Hematologii i Transfuzjologii
Warsaw, , Poland
Uniwersytecki Szpital Kliniczny im. J. Mikulicza-Radeckiego we Wroclawiu, PZOZ
Wroclaw, , Poland
Gachon University Gil Medical Center
Incheon, , South Korea
Seoul National University Hospital
Seoul, , South Korea
Severance Hospital, Yonsei University Health System
Seoul, , South Korea
Samsung Medical Center
Seoul, , South Korea
The Catholic University of Korea, Seoul St. Mary's Hospital
Seoul, , South Korea
Hospital Universitari Germans Trias I Pujol
Badalona, Barcelona, Spain
ICO l'Hospitalet- Hospital Duran i Reynals
L'Hospitalet de Llobregat, Barcelona, Spain
Clinica Universidad de Navarra
Pamplona, Navarre, Spain
Hospital Universitario de Cabuenes
Gijón, Principality of Asturias, Spain
Hospital de la Santa Creu i Sant Pau
Barcelona, , Spain
Hospital Universitario Ramon y Cajal
Madrid, , Spain
Fundacion Jimenez Diaz
Madrid, , Spain
Ondokuz Mayiz universitesi Tip Fakultesi
Kurupelit, Samsun, Turkey (Türkiye)
Gazi Universitesi Tip Fakultesi, Besevler
Ankara, , Turkey (Türkiye)
Dokuz Eylul Universitesi Tip Fakultesi
Izmir, , Turkey (Türkiye)
Namik Kemal Universitesi Saglik Uyg. ve.Ars. Hastanesi
Tekirdağ, , Turkey (Türkiye)
Communal Nonprofit enterprise Cherkasy Regional Oncology Dispensary ofCherkasy Oblast Council,Regional Treatment and Diagnostic Hematological Center
Cherkasy, , Ukraine
Communal Non-profit Enterprise Regional Center of Oncology, Department of Hematology
Kharkiv, , Ukraine
National Inst. of Cancer, Scientific and Research Dept of Chemotherapy of Hemoblastosis and Adjuvant Treatment Methods, Dept of Oncohematology with Sector of Adjuvant treatment methods
Kyiv, , Ukraine
SI national Scientific Center of Radiation Medicine of NAMS of Ukraine, Dep. of Radiation Oncohematology and Stem Cell Transplantation Unit
Kyiv, , Ukraine
Andrii Novak Transcarpathian Regional Clinical Hospital, Department of Hematology
Uzhhorod, , Ukraine
Communal Institution O.F. Herbachevskyi Regional Clinical Hospital of Zhytomyr Regional Council Dept of Hematology with beds of Intensive Therapy
Zhytomyr, , Ukraine
Barts Health NHS Trust
London, Greater London, United Kingdom
The Christie NHS Foundation Trust
Manchester, Greater Manchester, United Kingdom
Nottingham University Hospitals NHS Trust
Nottingham, Nottinghamshire, United Kingdom
The Churchill Hospital
Oxford, Oxfordshire, United Kingdom
The Royal Marsden NHS Foundation Trust
Sutton, Surrey, United Kingdom
St James University Hospital
Leeds, West Yorkshire, United Kingdom
University College London Hospitals NHS Foundation Trust
London, , United Kingdom
Countries
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References
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Wang M, Jurczak W, Trneny M, Belada D, Wrobel T, Ghosh N, Keating MM, van Meerten T, Alvarez RF, von Keudell G, Thieblemont C, Peyrade F, Andre M, Hoffmann M, Szafer-Glusman E, Lin J, Dean JP, Neuenburg JK, Tam CS. Ibrutinib plus venetoclax in relapsed or refractory mantle cell lymphoma (SYMPATICO): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2025 Feb;26(2):200-213. doi: 10.1016/S1470-2045(24)00682-X.
Wang M, Ramchandren R, Chen R, Karlin L, Chong G, Jurczak W, Wu KL, Bishton M, Collins GP, Eliadis P, Peyrade F, Lee Y, Eckert K, Neuenburg JK, Tam CS. Concurrent ibrutinib plus venetoclax in relapsed/refractory mantle cell lymphoma: the safety run-in of the phase 3 SYMPATICO study. J Hematol Oncol. 2021 Oct 30;14(1):179. doi: 10.1186/s13045-021-01188-x.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Other Identifiers
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2017-000129-12
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
PCYC-1143-CA
Identifier Type: -
Identifier Source: org_study_id
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