Study of Ibrutinib Combined With Venetoclax in Subjects With Mantle Cell Lymphoma (MCL) (SYMPATICO)

July 2, 2025 updated by: Pharmacyclics LLC.

Phase 3 Study of Ibrutinib in Combination With Venetoclax in Subjects With Mantle Cell Lymphoma

This Phase 3 multinational, randomized, double-blind study is designed to compare the efficacy and safety of the combination of ibrutinib and venetoclax vs. ibrutinib and placebo in subjects with MCL.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
366

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Australian Capital Territory
      • Canberra, Australian Capital Territory, Australia, 2605
        • The Canberra Hospital
    • New South Wales
      • Albury, New South Wales, Australia, 2640
        • Border Medical Oncology Research Unit
    • Queensland
      • Auchenflower, Queensland, Australia, 4101
        • ICON Cancer Care
    • Victoria
      • Heidelberg, Victoria, Australia, 3084
        • Austin Health
      • Melbourne, Victoria, Australia, 3000
        • Peter MacCallum Cancer
      • Melbourne, Victoria, Australia, 3065
        • St.Vincent's hospital
    • Western Australia
      • Nedlands, Western Australia, Australia, 6009
        • Sir Charles Gairdner Hospital
  • Belgium
      • Antwerpen, Belgium, 2060
        • ZiekenhuisNetwerk Antwerpen (ZNA) Stuivenberg
      • Brugge, Belgium, 8000
        • AZ Sint-Jan Brugge-Oostende AV
      • Bruxelles, Belgium, 1000
        • Institut Jules Bordet
      • Yvoir, Belgium, 5530
        • CHU UCL Namur asbl- Mont Godinne
  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 4N2
        • Tom Baker Cancer Centre
      • Edmonton, Alberta, Canada, T6G 1 Z2
        • Cross Cancer Institute
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 4E6
        • BC Cancer-Vancouver Centre
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3H 2Y9
        • Queen Elizabeth II Health Science Centre
    • Ontario
      • Ottawa, Ontario, Canada, K1H 8L6
        • The Ottawa Hospital
    • Quebec
      • Montréal, Quebec, Canada, H3T 1E2
        • Jewish General Hospital
  • Czechia
      • Brno, Czechia, 625 00
        • FN Brno, Interni hematologicka a onkologicka klinika
      • Hradec Králové, Czechia, 500 05
        • Fakultni Nemocnice (FN) Hradec Kravlove, a.s. IV. Interni hematologicka klinika
      • Olomouc, Czechia, 77900
        • FN Olomouc
      • Ostrava-Poruba, Czechia, 708 52
        • FN Ostrava
      • Praha 10, Czechia, 100 34
        • Fakultní Nemocnice Královské Vinohrady
      • Praha 2, Czechia, 128 08
        • Vseobecna fakultni nemocnice v Praze, l. interni klinika-klinika hematologie
  • France
      • Bordeaux, France, 33076
        • Institut Bergonie
      • Clermont Ferrand cedex, France, 63003
        • CHU Clermont Ferrand - Hôpital d'Estaing
      • Marseille, France, 13009
        • Institut Paoli Calmettes, Service Hematologie
      • Nice Cedex 2, France, 06189
        • Centre Antoine Lacassagne
      • Paris, France, 75010
        • Hopital Saint-Louis
      • Pierre Benite cedex, France, 69495
        • Centre Hospitalier Lyon Sud
      • Tours Cedex 01, France, 37044
        • CHU de Tours
    • Calvados
      • CAEN Cedex, Calvados, France, 14033
        • CHU CAEN-Hôpital de la Côte de Nacre
  • Germany
      • Berlin, Germany, 10967
        • Vivantes Klinikum am Urban
      • Berlin, Germany, 12200
        • Charite- Universitatsmedizin Berlin, Campus Benjamin Franklin
      • Essen, Germany, 45147
        • Universitätsklinikum Essen, Klinik für Hämatologie
      • Homburg/Saar, Germany, 66421
        • Universitatsklinikum des Saarlandes, Klinik fur Innere Medizin I
    • Baden-Wuttemberg
      • Mutlangen, Baden-Wuttemberg, Germany, 73557
        • Kliniken Ostalb Stauferklinikum Schwab. Gmund
      • Ulm, Baden-Wuttemberg, Germany, 89081
        • Universitaetsklinikum Ulm
    • Bayern
      • Muenchen, Bayern, Germany, 81377
        • Klinikum der Universitaet Muenchen Campus Grosshadern
    • Koln
      • Kerpen, Koln, Germany, 50937
        • Universitätsklinikum Köln
    • Mainz
      • Langen, Mainz, Germany, 55131
        • Universitaetsmedizin der Johannes Gutenberg, Langenbeckstrasse 1
    • Sachsen
      • Dresden, Sachsen, Germany, 01307
        • Gemeinschaftpraxis Haematologie und Onkologie
  • Greece
      • Alexandroupolis, Greece, 68100
        • University Hospital of Alexandroupolis
      • Athens, Greece, 11527
        • General Hospital of Athens Laiko
      • Athens, Greece, 11528
        • General Hospital of Athens "Alexandra"
      • Athens, Greece, 11525
        • 251 Air Force General Hospital
      • Ioánnina, Greece, 45500
        • University General Hospital of Ioannina
      • Larissa, Greece, 41110
        • University General Hospital of Larissa
      • Patra, Greece, 26504
        • University Hospital of Patras
  • Hungary
      • Budapest, Hungary, 1122
        • Országos Onkológiai Intézet
      • Budapest, Hungary, 1125
        • Semmelweis Egyetem
      • Debrecen, Hungary, 4032
        • Debreceni Egyetem Klinikai Kozpont, Belgyogyaszati Klinika
      • Győr, Hungary, 9024
        • Petz Aladar Megyei Oktato Korhaz, II. Belgyogyaszat-Hematologia
      • Kaposvár, Hungary, 7400
        • Somogy Megyei Kaposi Mor Oktato Korhaz
      • Szeged, Hungary, 6725
        • Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ
      • Szombathely, Hungary, 9700
        • Markusovszky Egyetemi Oktatokorhaz, Haematologiai es Haemoszatazeologiai Osztaly
  • Italy
    • Alessandria/Piemonte
      • Alessandria, Alessandria/Piemonte, Italy, 15121
        • Azienda Ospedaliera SS Antonio e Biagio e Cesare Arrigo di Alessandria
    • Bergamo/Lombardia
      • Bergamo, Bergamo/Lombardia, Italy, 21427
        • Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni XXIII)
    • Bologna/Emilia-Romagna
      • Bologna, Bologna/Emilia-Romagna, Italy, 40138
        • Azienda Ospedaliera Universitaria di Bologna Policlinico Saint Orsola Malpighi
    • Brescia/Lombardia
      • Brescia, Brescia/Lombardia, Italy, 25123
        • Asst Degli Spedali Civili Di Brescia
    • Cuneo/Piemonte
      • Cuneo, Cuneo/Piemonte, Italy, 12100
        • Azienda Ospedaliera S. Croce e Carle Cuneo
    • Forli-Cesena/Emilia-Rom
      • Meldola, Forli-Cesena/Emilia-Rom, Italy, 47014
        • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
    • Milano/Lombardia
      • Milano, Milano/Lombardia, Italy, 20132
        • IRCCS Ospedale S. Raffaele di Milano
      • Milano, Milano/Lombardia, Italy, 20162
        • Asst Grande Ospedale Metropolitano Niguarda
    • Pavia/Lombardia
      • Pavia, Pavia/Lombardia, Italy, 27100
        • Fondazione IRCCS Policlinico San Matteo
    • Torino/Piemonte
      • Torino, Torino/Piemonte, Italy, 10126
        • Azienda Ospedaliero Universitaria Molinette San Giovanni Battista di Torino
    • Udine/Friuli-Venezia Giulia
      • Udine, Udine/Friuli-Venezia Giulia, Italy, 33010
        • Azienda Ospedaliero-Universitaria Santa Maria della Misericordia
  • Korea, Republic of
      • Incheon, Korea, Republic of, 21565
        • Gachon University Gil Medical Center
      • Seoul, Korea, Republic of, 03080
        • Seoul National University Hospital
      • Seoul, Korea, Republic of, 03722
        • Severance Hospital, Yonsei University Health System
      • Seoul, Korea, Republic of, 06591
        • The Catholic University of Korea, Seoul St. Mary's Hospital
      • Seoul, Korea, Republic of, 06351
        • Samsung Medical Center
  • Netherlands
      • Groningen, Netherlands, 9713 GZ
        • Universitair Medisch Centrum Groningen
      • Hoofddorp, Netherlands, 2134 TM
        • Spaarne Gasthuis
      • Leiden, Netherlands, 2333 ZA
        • Leiden University Medical Center
      • Rotterdam, Netherlands, 3015 CE
        • Erasmus MC
      • Schiedam, Netherlands, 3118 JH
        • Franciscus Vlietland
  • Poland
      • Bydgoszcz, Poland, 85-168
        • Szpital Uniwersytecki nr 2 im. dr J. Biziela w Bydgoszcz
      • Chorzów, Poland, 41-500
        • Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich, Oddzial Hematologiczny
      • Kraków, Poland, 30-510Komisja Bioctyczn
        • Malopolskie Centrum Medyczne s c
      • Warszawa, Poland, 02-776
        • Instytut Hematologii I Transfuzjologii
      • Wrocław, Poland, 50-367
        • Uniwersytecki Szpital Kliniczny im. J. Mikulicza-Radeckiego we Wroclawiu, PZOZ
      • Łódź, Poland, 93-513
        • Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. Kopernika w Lodzi
  • Spain
      • Barcelona, Spain, 08041
        • Hospital De La Santa Creu I Sant Pau
      • Madrid, Spain, 28040
        • Fundacion Jimenez Diaz
      • Madrid, Spain, 28034
        • Hospital Universitario Ramon y Cajal
    • Asturias
      • Gijón, Asturias, Spain, 33203
        • Hospital Universitario de Cabueñes
    • Barcelona
      • Badalona, Barcelona, Spain, 08916
        • Hospital Universitari Germans Trias i Pujol
      • L'Hospitalet De Llobregat, Barcelona, Spain, 08907
        • ICO l'Hospitalet- Hospital Duran i Reynals
    • Navarra
      • Pamplona, Navarra, Spain, 31008
        • Clinica Universidad de Navarra
  • Turkey
      • Ankara, Turkey, 06500
        • Gazi Universitesi Tip Fakultesi, Besevler
      • Tekirdağ, Turkey, 59030
        • Namik Kemal Universitesi Saglik Uyg. ve.Ars. Hastanesi
      • İzmir, Turkey
        • Dokuz Eylul Universitesi Tip Fakultesi
    • Samsun
      • Kurupelit, Samsun, Turkey, 55139
        • Ondokuz Mayiz universitesi Tip Fakultesi
  • Ukraine
      • Cherkasy, Ukraine, 18009
        • Communal Nonprofit enterprise Cherkasy Regional Oncology Dispensary ofCherkasy Oblast Council,Regional Treatment and Diagnostic Hematological Center
      • Kharkiv, Ukraine, 61070
        • Communal Non-profit Enterprise Regional Center of Oncology, Department of Hematology
      • Kyiv, Ukraine, 03022
        • 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, 03115
        • SI national Scientific Center of Radiation Medicine of NAMS of Ukraine, Dep. of Radiation Oncohematology and Stem Cell Transplantation Unit
      • Uzhgorod, Ukraine, 88018
        • Andrii Novak Transcarpathian Regional Clinical Hospital, Department of Hematology
      • Zhytomyr, Ukraine, 10002
        • Communal Institution O.F. Herbachevskyi Regional Clinical Hospital of Zhytomyr Regional Council Dept of Hematology with beds of Intensive Therapy
  • United Kingdom
      • London, United Kingdom, NW1 2PG
        • University College London Hospitals NHS Foundation Trust
    • Greater London
      • London, Greater London, United Kingdom, EC1A 7BE
        • Barts Health NHS Trust
    • Greater Manchester
      • Manchester, Greater Manchester, United Kingdom, M20 4BX
        • The Christie NHS Foundation Trust
    • Nottinghamshire
      • Nottingham, Nottinghamshire, United Kingdom, NG5 1PB
        • Nottingham University Hospitals Nhs Trust
    • Oxfordshire
      • Oxford, Oxfordshire, United Kingdom, OX3 7LE
        • The Churchill Hospital
    • Surrey
      • Sutton, Surrey, United Kingdom, SM2 5PT
        • The Royal Marsden NHS Foundation Trust
    • West Yorkshire
      • Leeds, West Yorkshire, United Kingdom, LS9 7TF
        • St James University Hospital
  • United States
    • Arizona
      • Tucson, Arizona, United States, 85719
        • The University of Arizona Cancer Centre-North Campus
    • California
      • Duarte, California, United States, 91010
        • City of Hope
      • Los Angeles, California, United States, 90095
        • UCLA Department of Medicine-Hematology/Oncology
    • Florida
      • Orlando, Florida, United States, 32806
        • Orlando Health Inc.
    • Kansas
      • Westwood, Kansas, United States, 66205
        • The University of Kansas Cancer Center and Medical Pavilion
    • Kentucky
      • Louisville, Kentucky, United States, 40207
        • Norton Cancer Institute
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Barbara Ann Karmanos Cancer Institute
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
      • New York, New York, United States, 11794
        • Stony Brook University
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
        • Levine Cancer Institute
    • Tennessee
      • Chattanooga, Tennessee, United States, 37404
        • Tennessee Oncology
      • Knoxville, Tennessee, United States, 37920
        • University of Tennessee Medical Center
    • Texas
      • Houston, Texas, United States, 77030
        • University of Texas MD Anderson Cancer Center
    • Washington
      • Seattle, Washington, United States, 98194
        • Swedish Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Relapsed/Refractory Arm

Inclusion Criteria:

  • Pathologically confirmed MCL (in 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).
  • 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.

Exclusion Criteria:

  • History or current evidence of central nervous system lymphoma.
  • 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

Inclusion Criteria:

  • 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:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 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.
Drug: Ibrutinib
Administered orally once daily
Drug: Venetoclax
Administered orally once daily
Experimental: 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.
Drug: Ibrutinib
Administered orally once daily
Drug: Venetoclax
Administered orally once daily
Placebo Comparator: 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.
Drug: Ibrutinib
Administered orally once daily
Drug: Placebo Oral tablet to match Venetoclax
Administered orally once daily
Experimental: Treatment-naive Open-label Arm
Participants are treated with ibrutinib 560 mg and venetoclax 400 mg, administered using the 5-week ramp-up schedule.
Drug: Ibrutinib
Administered orally once daily
Drug: Venetoclax
Administered orally once daily

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Tumor Lysis Syndrome (TLS) Events (Safety Run-in)
Time Frame: After at least 3 months of treatment, with an overall median treatment duration of 20.0 months

TLS events are defined as follows:

  • Clinical TLS: any event that meets Howard criteria (N Engl J Med 2011;364:1844-1854) with the following exceptions:

    • For the purpose of TLS assessment during the Safety Run-in Period, only those increases in serum creatinine > 1.0 mg/dL from pre-treatment baseline will be considered clinical TLS.
    • In participants with renal dysfunction at baseline (CrCl < 60 mL/min), clinical TLS is defined as the presence of laboratory TLS plus either seizures, cardiac dysrhythmia, or death.
  • Laboratory TLS: any event that meets Howard criteria (N Engl J Med 2011;364:1844-1854) for laboratory TLS, that does not resolve within 72 hours despite protocol required management.
After at least 3 months of treatment, with an overall median treatment duration of 20.0 months
Number of Participants With Dose Limiting Toxicities (DLT) (Safety Run-in)
Time Frame: After at least 3 months of treatment, with an overall median treatment duration of 20.0 months

DLT: any Grade (Gr) 3 or higher non-TLS adverse event (AE) at least possibly related to study drug occurring during the DLT assessment period with the following clarifications:

Non-Hematologic DLTs: Gr ≥3 nausea, vomiting or diarrhea uncontrolled despite maximum medical supportive care and persisting >5 days; Gr 3 fatigue persisting >7 days; Gr 3 infection is not a DLT, however an infection with lifethreatening consequences or requiring urgent intervention (Gr 4) was considered a DLT; Treatment delay of any study drug >7 days for toxicity.

Hematologic DLTs: Gr 3 neutropenia is not a DLT, however, Gr 4 neutropenia (ANC <500/mm^3) lasting for > 7 days is a DLT; Gr 3 or 4 neutropenia complicated by fever ≥38.5°C or infection; Gr 4 thrombocytopenia (<25,000/mm^3) that persists for > 7 days; Gr 3 or 4 thrombocytopenia associated with Gr 2 or greater bleeding; Gr 3 anemia is not a DLT, however, Gr 4 anemia is a DLT; Treatment delay of any study drug >7 days for hematologic toxicity.
After at least 3 months of treatment, with an overall median treatment duration of 20.0 months
Number of Participants With Treatment Emergent Adverse Events (TEAEs) (Safety Run-in)
Time Frame: From first dose of study drug until the end of treatment + 30 days, with an overall median treatment duration of 20.0 months
AE: any untoward medical occurrence in a participant that does not necessarily have a causal relationship with treatment. The investigator assesses the relationship of each event to the use of study. Serious adverse event (SAE): an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs): any event that began or worsened in severity on or after the first dose of study drug. Event severity is graded as mild (1), moderate (2), severe (3), life threatening (4), death (5).
From first dose of study drug until the end of treatment + 30 days, with an overall median treatment duration of 20.0 months
Progression-free Survival (PFS) (Randomization Phase)
Time Frame: For an overall median time on study of 61.34 months
PFS is defined as the time from the date of randomization to the date of disease progression using the Revised Response Criteria for Malignant Lymphoma (Cheson 2014), or death from any cause, whichever occurs first.
For an overall median time on study of 61.34 months
Complete Response (CR) Rate (Treatment-Naive Arm)
Time Frame: For an overall median time on study of 40.51 months
CR rate is defined as the percentage of participants with a CR according to the Revised Response Criteria for Malignant Lymphoma (Cheson 2014).
For an overall median time on study of 40.51 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Overall Survival (OS) (Safety Run-in)
Time Frame: For an overall median time on study of 74.78 months
OS is defined as the time from the date of the first dose of study treatment to death from any cause.
For an overall median time on study of 74.78 months
Progression-free Survival (PFS) (Safety Run-in)
Time Frame: For an overall median time on study of 74.78 months
PFS is defined as the time from the date of the first dose of study treatment to the date of disease progression using the Revised Response Criteria for Malignant Lymphoma (Cheson 2014), or death from any cause, whichever occurs first.
For an overall median time on study of 74.78 months
Duration of Response (DOR) (Safety Run-in)
Time Frame: For an overall median time on study of 74.78 months
DOR is defined for participants who achieve an overall response as the time from the first occurrence of response (CR or PR according to the Revised Response Criteria for Malignant Lymphoma [Cheson 2014]) to disease progression or death, whichever occurs first.
For an overall median time on study of 74.78 months
Overall Response Rate (ORR) (Safety Run-in)
Time Frame: For an overall median time on study of 74.78 months
ORR is defined as the percentage of participants with CR or PR per investigator assessment according to the Revised Response Criteria for Malignant Lymphoma (Cheson 2014).
For an overall median time on study of 74.78 months
Percentage of Participants With a Complete Response (CR) (Randomization Phase)
Time Frame: For an overall median time on study of 61.34 months
Complete response rate (CR) based on the best overall response per investigator assessment according to the Revised Response Criteria for Malignant Lymphoma (Cheson 2014).
For an overall median time on study of 61.34 months
Overall Response Rate (ORR) (Randomization Phase and Treatment-Naive Arm)
Time Frame: For an overall median time on study of 61.34 months (Randomization Phase) and 40.51 months (Treatment-Naïve arm)
ORR is defined as the percentage of participants with CR or PR per investigator assessment according to the Revised Response Criteria for Malignant Lymphoma (Cheson 2014).
For an overall median time on study of 61.34 months (Randomization Phase) and 40.51 months (Treatment-Naïve arm)
MRD-negative Remission Rate in Participants Who Achieve CR Per Investigator Assessment (Randomization Phase and Treatment-Naive Arm)
Time Frame: For an overall median time on study of 61.34 months (Randomization Phase) and 40.51 months (Treatment-Naïve arm)
MRD-negative remission rate is defined as the percentage of participants with undetectable MRD at documented CR in participants who were MRD positive at screening as assessed by flow cytometry in bone marrow and/or peripheral blood, with requirement of confirmation of MRD negativity in the subsequent peripheral blood 12 weeks later.
For an overall median time on study of 61.34 months (Randomization Phase) and 40.51 months (Treatment-Naïve arm)
Overall Survival (OS) (Randomization Phase and Treatment-Naive Arm)
Time Frame: For an overall median time on study of 61.34 months (Randomization Phase) and 40.51 months (Treatment-Naïve arm)
OS is defined as the time from the date of randomization (Randomization Phase) or the first dose of study treatment (Treatment-Naïve arm) to death from any cause.
For an overall median time on study of 61.34 months (Randomization Phase) and 40.51 months (Treatment-Naïve arm)
Duration of Response (DOR) (Randomization Phase and Treatment-Naive Arm)
Time Frame: For an overall median time on study of 61.34 months (Randomization Phase) and 40.51 months (Treatment-Naïve arm)
DOR is defined as the time frame for participants who achieve an overall response as the time from the first occurrence of response (CR or PR according to the Revised Response Criteria for Malignant Lymphoma [Cheson 2014]) to disease progression or death, whichever occurs first.
For an overall median time on study of 61.34 months (Randomization Phase) and 40.51 months (Treatment-Naïve arm)
Time to Next Treatment (TTNT) (Randomization Phase and Treatment-Naive Arm)
Time Frame: For an overall median time on study of 61.34 months (Randomization Phase) and 40.51 months (Treatment-Naïve arm)
TTNT is defined as the duration from the date of randomization (Randomization Phase) or date of first dose of study treatment (Treatment-Naive Arm) to the start date of any anti-lymphoma treatment subsequent to study treatment. Post-treatment stem cell transplantation, chimeric antigen receptor (CAR) T-cell therapy, or other cellular therapies were not considered subsequent anti-cancer treatments for participants responding to the study treatment (CR or PR).
For an overall median time on study of 61.34 months (Randomization Phase) and 40.51 months (Treatment-Naïve arm)
Number of Participants With TEAEs (Randomization Phase)
Time Frame: From first dose of study drug until the end of treatment + 30 days, with an overall median treatment duration of 19.5 months
AE: any untoward medical occurrence in a participant that does not necessarily have a causal relationship with treatment. The investigator assesses the relationship of each event to the use of study. Serious adverse event (SAE): an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs): any event that began or worsened in severity on or after the first dose of study drug. Event severity is graded as mild (1), moderate (2), severe (3), life threatening (4), death (5).
From first dose of study drug until the end of treatment + 30 days, with an overall median treatment duration of 19.5 months
Number of Participants With TLS TEAEs (Randomization Phase)
Time Frame: From first dose of study drug until the end of treatment + 7 days, with an overall median treatment duration 19.5 months
Treatment-emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs): any event that began or worsened in severity on or after the first dose of study drug (SD). Event severity is graded as mild (1), moderate (2), severe (3), life threatening (4), death (5).
From first dose of study drug until the end of treatment + 7 days, with an overall median treatment duration 19.5 months
Steady-State Pharmacokinetics (PK) of Ibrutinib: Maximum Observed Plasma Concentration (Cmax) (Randomization Phase)
Time Frame: Week 6, Day 1: Predose, at Dose, 1 hour (± 15 minutes [min]), 2 hours (± 15 min), 4 hours (± 30 min), 6 hours (± 30 min), 8 hours (± 1 hour), 24 hours post-dose
Pre-dose concentrations were applied as 24-hour concentrations in order to calculate steady-state PK parameters.
Week 6, Day 1: Predose, at Dose, 1 hour (± 15 minutes [min]), 2 hours (± 15 min), 4 hours (± 30 min), 6 hours (± 30 min), 8 hours (± 1 hour), 24 hours post-dose
Steady-State PK of Ibrutinib: Time to Cmax (Tmax) (Randomization Phase)
Time Frame: Week 6, Day 1: Predose, at Dose, 1 hour (± 15 minutes [min]), 2 hours (± 15 min), 4 hours (± 30 min), 6 hours (± 30 min), 8 hours (± 1 hour), 24 hours post-dose
Pre-dose concentrations were applied as 24-hour concentrations in order to calculate steady-state PK parameters.
Week 6, Day 1: Predose, at Dose, 1 hour (± 15 minutes [min]), 2 hours (± 15 min), 4 hours (± 30 min), 6 hours (± 30 min), 8 hours (± 1 hour), 24 hours post-dose
Steady-State PK of Ibrutinib: Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Measurable Concentration (AUClast) (Randomization Phase)
Time Frame: Week 6, Day 1: Predose, at Dose, 1 hour (± 15 minutes [min]), 2 hours (± 15 min), 4 hours (± 30 min), 6 hours (± 30 min), 8 hours (± 1 hour), 24 hours post-dose
Pre-dose concentrations were applied as 24-hour concentrations in order to calculate steady-state PK parameters.
Week 6, Day 1: Predose, at Dose, 1 hour (± 15 minutes [min]), 2 hours (± 15 min), 4 hours (± 30 min), 6 hours (± 30 min), 8 hours (± 1 hour), 24 hours post-dose
Steady-State PK of Ibrutinib: Terminal Elimination Half-Life (t1/2,Term) (Randomization Phase)
Time Frame: Week 6, Day 1: Predose, at Dose, 1 hour (± 15 minutes [min]), 2 hours (± 15 min), 4 hours (± 30 min), 6 hours (± 30 min), 8 hours (± 1 hour), 24 hours post-dose
Pre-dose concentrations were applied as 24-hour concentrations in order to calculate steady-state PK parameters.
Week 6, Day 1: Predose, at Dose, 1 hour (± 15 minutes [min]), 2 hours (± 15 min), 4 hours (± 30 min), 6 hours (± 30 min), 8 hours (± 1 hour), 24 hours post-dose
Steady-State PK of Ibrutinib: Time of Last Measurable Concentration (Tlast) (Randomization Phase)
Time Frame: Week 6, Day 1: Predose, at Dose, 1 hour (± 15 minutes [min]), 2 hours (± 15 min), 4 hours (± 30 min), 6 hours (± 30 min), 8 hours (± 1 hour), 24 hours post-dose
Pre-dose concentrations were applied as 24-hour concentrations in order to calculate steady-state PK parameters.
Week 6, Day 1: Predose, at Dose, 1 hour (± 15 minutes [min]), 2 hours (± 15 min), 4 hours (± 30 min), 6 hours (± 30 min), 8 hours (± 1 hour), 24 hours post-dose
Steady-State PK of Ibrutinib: Area Under the Concentration-Time Curve From 0-24 Hours (AUC0-24) (Randomization Phase)
Time Frame: Week 6, Day 1: Predose, at Dose, 1 hour (± 15 minutes [min]), 2 hours (± 15 min), 4 hours (± 30 min), 6 hours (± 30 min), 8 hours (± 1 hour), 24 hours post-dose
Pre-dose concentrations were applied as 24-hour concentrations in order to calculate steady-state PK parameters.
Week 6, Day 1: Predose, at Dose, 1 hour (± 15 minutes [min]), 2 hours (± 15 min), 4 hours (± 30 min), 6 hours (± 30 min), 8 hours (± 1 hour), 24 hours post-dose
Steady-State PK of Ibrutinib: Terminal Elimination Rate Constant (λz) (Randomization Phase)
Time Frame: Week 6, Day 1: Predose, at Dose, 1 hour (± 15 minutes [min]), 2 hours (± 15 min), 4 hours (± 30 min), 6 hours (± 30 min), 8 hours (± 1 hour), 24 hours post-dose
Pre-dose concentrations were applied as 24-hour concentrations in order to calculate steady-state PK parameters.
Week 6, Day 1: Predose, at Dose, 1 hour (± 15 minutes [min]), 2 hours (± 15 min), 4 hours (± 30 min), 6 hours (± 30 min), 8 hours (± 1 hour), 24 hours post-dose
Steady-State PK of Ibrutinib: Apparent Total Clearance at Steady State (CLss/F) (Randomization Phase)
Time Frame: Week 6, Day 1: Predose, at Dose, 1 hour (± 15 minutes [min]), 2 hours (± 15 min), 4 hours (± 30 min), 6 hours (± 30 min), 8 hours (± 1 hour), 24 hours post-dose
Pre-dose concentrations were applied as 24-hour concentrations in order to calculate steady-state PK parameters.
Week 6, Day 1: Predose, at Dose, 1 hour (± 15 minutes [min]), 2 hours (± 15 min), 4 hours (± 30 min), 6 hours (± 30 min), 8 hours (± 1 hour), 24 hours post-dose
Steady-State PK of Venetoclax: Cmax (Randomization Phase)
Time Frame: Week 6, Day 1: Predose, at Dose, 1 hour (± 15 minutes [min]), 2 hours (± 15 min), 4 hours (± 30 min), 6 hours (± 30 min), 8 hours (± 1 hour), 24 hours post-dose
Pre-dose concentrations were applied as 24-hour concentrations in order to calculate steady-state PK parameters.
Week 6, Day 1: Predose, at Dose, 1 hour (± 15 minutes [min]), 2 hours (± 15 min), 4 hours (± 30 min), 6 hours (± 30 min), 8 hours (± 1 hour), 24 hours post-dose
Steady-State PK of Venetoclax: AUC0-24 (Randomization Phase)
Time Frame: Week 6, Day 1: Predose, at Dose, 1 hour (± 15 minutes [min]), 2 hours (± 15 min), 4 hours (± 30 min), 6 hours (± 30 min), 8 hours (± 1 hour), 24 hours post-dose
Pre-dose concentrations were applied as 24-hour concentrations in order to calculate steady-state PK parameters.
Week 6, Day 1: Predose, at Dose, 1 hour (± 15 minutes [min]), 2 hours (± 15 min), 4 hours (± 30 min), 6 hours (± 30 min), 8 hours (± 1 hour), 24 hours post-dose
Steady-State PK of Venetoclax: Time to Cmax (Tmax) (Randomization Phase)
Time Frame: Week 6, Day 1: Predose, at Dose, 1 hour (± 15 minutes [min]), 2 hours (± 15 min), 4 hours (± 30 min), 6 hours (± 30 min), 8 hours (± 1 hour), 24 hours post-dose
Pre-dose concentrations were applied as 24-hour concentrations in order to calculate steady-state PK parameters.
Week 6, Day 1: Predose, at Dose, 1 hour (± 15 minutes [min]), 2 hours (± 15 min), 4 hours (± 30 min), 6 hours (± 30 min), 8 hours (± 1 hour), 24 hours post-dose
Steady-State PK of Venetoclax: CLss/F (Randomization Phase)
Time Frame: Week 6, Day 1: Predose, at Dose, 1 hour (± 15 minutes [min]), 2 hours (± 15 min), 4 hours (± 30 min), 6 hours (± 30 min), 8 hours (± 1 hour), 24 hours post-dose
Pre-dose concentrations were applied as 24-hour concentrations in order to calculate steady-state PK parameters.
Week 6, Day 1: Predose, at Dose, 1 hour (± 15 minutes [min]), 2 hours (± 15 min), 4 hours (± 30 min), 6 hours (± 30 min), 8 hours (± 1 hour), 24 hours post-dose
Time to Worsening in Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Subscale of the Health-related Quality of Life (Randomization Phase)
Time Frame: For an overall median time on study of 61.34 months (Randomization Phase)
The FACT-Lym lymphoma-specific additional concerns subscale responses to all items are rated on a 5-point scale ranging from 0 "not at all" to 4 "very much". The lymphoma subscale includes 15 items and scores range from 0 to 60, with higher scores representing better functional status and well-being. A 5-point change in the Lym subscale was selected as a conservative estimate of clinically meaningful deterioration in lymphoma symptoms.
For an overall median time on study of 61.34 months (Randomization Phase)
Duration of CR (Treatment-Naive Arm)
Time Frame: For an overall median time on study of 40.51 months
Duration of CR, defined for subjects who achieve CR according to the Revised Response Criteria for Malignant Lymphoma (Cheson 2014) as the time from the first occurrence of CR to disease progression or death, whichever occurs first.
For an overall median time on study of 40.51 months
Progression-free Survival (PFS) (Treatment-Naive Arm)
Time Frame: For an overall median time on study of 40.51 months
PFS is defined as the time from the date of the first dose of study treatment to the date of disease progression using the Revised Response Criteria for Malignant Lymphoma (Cheson 2014), or death from any cause, whichever occurs first.
For an overall median time on study of 40.51 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Pharmacyclics LLC.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Janssen Research & Development, LLC

Publications and helpful links

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General Publications

Study record dates

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Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 19, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 26, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 27, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 4, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 7, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 13, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 22, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 2, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PCYC-1143-CA
  • 2017-000129-12 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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