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Mantle-Cell LymphomaPhase 3SYMPATICONCT03112174

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

A Phase 3 study testing Ibrutinib and Venetoclax in people with Mantle-Cell Lymphoma, run by Pharmacyclics LLC. at 120 sites in 17 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Mantle-Cell Lymphoma
What is being tested?
Ibrutinib and Venetoclax
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
366 participants
Where
120 sitesin 17 countries
Study dates
19 Jun 2017to 27 Jun 2024
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

  • 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.
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  • 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.

Who cannot join

  • 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
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  • 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.

Trial locations and contacts

120 sites in 17 countries.

120 sites in 17 countries

United States14 sites

  • Levine Cancer Institute

    Charlotte, North Carolina, 28204

  • Tennessee Oncology

    Chattanooga, Tennessee, 37404

  • Barbara Ann Karmanos Cancer institute

    Detroit, Michigan, 48201

  • City of Hope

    Duarte, California, 91010

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • University of Tennessee medical Center

    Knoxville, Tennessee, 37920

  • UCLA Department of Medicine-Hematology/Oncology

    Los Angeles, California, 90095

  • Norton Cancer Institute

    Louisville, Kentucky, 40207

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Stony Brook University

    New York, New York, 11794

  • Orlando Health Inc.

    Orlando, Florida, 32806

  • Swedish Cancer Institute

    Seattle, Washington, 98194

  • The University of Arizona Cancer Centre-North Campus

    Tucson, Arizona, 85719

  • The University of Kansas Cancer Center and Medical Pavilion

    Westwood, Kansas, 66205

Other trials in United States

Italy11 sites

  • Azienda Ospedaliera SS Antonio e Biagio e Cesare Arrigo di Alessandria

    Alessandria, Alessandria/Piemonte, 15121

  • Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni XXIII)

    Bergamo, Bergamo/Lombardia, 21427

  • Azienda Ospedaliera Universitaria di Bologna Policlinico Saint Orsola Malpighi

    Bologna, Bologna/Emilia-Romagna, 40138

  • ASST degli Spedali Civili di Brescia

    Brescia, Brescia/Lombardia, 25123

  • Azienda Ospedaliera S. Croce e Carle Cuneo

    Cuneo, Cuneo/Piemonte, 12100

  • Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori

    Meldola, Forli-Cesena/Emilia-Rom, 47014

  • IRCCS Ospedale S. Raffaele di Milano

    Milan, Milano/Lombardia, 20132

  • Asst Grande Ospedale Metropolitano Niguarda

    Milan, Milano/Lombardia, 20162

  • Fondazione IRCCS Policlinico San Matteo

    Pavia, Pavia/Lombardia, 27100

  • Azienda Ospedaliero Universitaria Molinette San Giovanni Battista di Torino

    Torino, Torino/Piemonte, 10126

  • Azienda Ospedaliero-Universitaria Santa Maria della Misericordia

    Udine, Udine/Friuli-Venezia Giulia, 33010

Other trials in Italy

Germany10 sites

  • Vivantes Klinikum Am Urban

    Berlin, 10967

  • Charite- Universitatsmedizin Berlin, Campus Benjamin Franklin

    Berlin, 12200

  • Gemeinschaftpraxis Haematologie und Onkologie

    Dresden, Saxony, 01307

  • Universitatsklinikum Essen, Klinik fur Hamatologie

    Essen, 45147

  • Universitatsklinikum des Saarlandes, Klinik fur Innere Medizin I

    Homburg/Saar, 66421

  • Universitatsklinikum Koln

    Kerpen, Koln, 50937

  • Universitaetsmedizin der Johannes Gutenberg, Langenbeckstrasse 1

    Langen, Mainz, 55131

  • Klinikum der Universitaet Muenchen Campus Grosshadern

    Munich, Bavaria, 81377

  • Kliniken Ostalb Stauferklinikum Schwab. Gmund

    Mutlangen, Baden-Wuttemberg, 73557

  • Universitaetsklinikum Ulm

    Ulm, Baden-Wuttemberg, 89081

Other trials in Germany

France8 sites

  • Institut Bergonié

    Bordeaux, 33076

  • CHU CAEN-Hôpital de la Côte de Nacre

    Caen, Calvados, 14033

  • CHU Clermont Ferrand - Hôpital d'Estaing

    Clermont-Ferrand, 63003

  • Institut Paoli Calmettes, Service Hematologie

    Marseille, 13009

  • Centre Antoine Lacassagne

    Nice, 06189

  • Hôpital Saint-Louis

    Paris, 75010

  • Centre Hospitalier Lyon Sud

    Pierre-Bénite, 69495

  • CHU de Tours

    Tours, 37044

Other trials in France

Australia7 sites

  • Border Medical Oncology Research Unit

    Albury, New South Wales, 2640

  • Icon Cancer Care

    Auchenflower, Queensland, 4101

  • The Canberra Hospital

    Canberra, Australian Capital Territory, 2605

  • Austin Health

    Heidelberg, Victoria, 3084

  • Peter MacCallum Cancer

    Melbourne, Victoria, 3000

  • St.Vincent's Hospital

    Melbourne, Victoria, 3065

  • Sir Charles Gairdner Hospital

    Nedlands, Western Australia, 6009

Other trials in Australia

Greece7 sites

  • University Hospital of Alexandroupolis

    Alexandroupoli, 68100

  • 251 Air Force General Hospital

    Athens, 11525

  • General Hospital of Athens Laiko

    Athens, 11527

  • General Hospital of Athens "Alexandra"

    Athens, 11528

  • University General Hospital of Ioannina

    Ioannina, 45500

  • University General Hospital of Larissa

    Larissa, 41110

  • University Hospital of Patras

    Pátrai, 26504

Other trials in Greece

Hungary7 sites

  • Orszagos Onkologiai Intezet

    Budapest, 1122

  • Semmelweis Egyetem

    Budapest, 1125

  • Debreceni Egyetem Klinikai Kozpont, Belgyogyaszati Klinika

    Debrecen, 4032

  • Petz Aladar Megyei Oktato Korhaz, II. Belgyogyaszat-Hematologia

    Győr, 9024

  • Somogy Megyei Kaposi Mor Oktato Korhaz

    Kaposvár, 7400

  • Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ

    Szeged, 6725

  • Markusovszky Egyetemi Oktatokorhaz, Haematologiai es Haemoszatazeologiai Osztaly

    Szombathely, 9700

Other trials in Hungary

Spain7 sites

  • Hospital Universitari Germans Trias I Pujol

    Badalona, Barcelona, 08916

  • Hospital de la Santa Creu i Sant Pau

    Barcelona, 08041

  • Hospital Universitario de Cabuenes

    Gijón, Principality of Asturias, 33203

  • ICO l'Hospitalet- Hospital Duran i Reynals

    L'Hospitalet de Llobregat, Barcelona, 08907

  • Hospital Universitario Ramon y Cajal

    Madrid, 28034

  • Fundacion Jimenez Diaz

    Madrid, 28040

  • Clinica Universidad de Navarra

    Pamplona, Navarre, 31008

Other trials in Spain

United Kingdom7 sites

  • St James University Hospital

    Leeds, West Yorkshire, LS9 7TF

  • Barts Health NHS Trust

    London, Greater London, EC1A 7BE

  • University College London Hospitals NHS Foundation Trust

    London, NW1 2PG

  • The Christie NHS Foundation Trust

    Manchester, Greater Manchester, M20 4BX

  • Nottingham University Hospitals NHS Trust

    Nottingham, Nottinghamshire, NG5 1PB

  • The Churchill Hospital

    Oxford, Oxfordshire, OX3 7LE

  • The Royal Marsden NHS Foundation Trust

    Sutton, Surrey, SM2 5PT

Other trials in United Kingdom

Canada6 sites

  • Tom Baker Cancer Centre

    Calgary, Alberta, T2N 4N2

  • Cross Cancer Institute

    Edmonton, Alberta, T6G 1 Z2

  • Queen Elizabeth II Health Science Centre

    Halifax, Nova Scotia, B3H 2Y9

  • Jewish General Hospital

    Montreal, Quebec, H3T 1E2

  • The Ottawa Hospital

    Ottawa, Ontario, K1H 8L6

  • BC Cancer-Vancouver Centre

    Vancouver, British Columbia, V5Z 4E6

Other trials in Canada

Czechia6 sites

  • FN Brno, Interni hematologicka a onkologicka klinika

    Brno, 625 00

  • Fakultni Nemocnice (FN) Hradec Kravlove, a.s. IV. Interni hematologicka klinika

    Hradec Králové, 500 05

  • FN Olomouc

    Olomouc, 77900

  • FN Ostrava

    Ostrava-Poruba, 708 52

  • Fakultni nemocnice Kralovske Vinohrady

    Prague, 100 34

  • Vseobecna fakultni nemocnice v Praze, l. interni klinika-klinika hematologie

    Prague, 128 08

Other trials in Czechia

Poland6 sites

  • Szpital Uniwersytecki nr 2 im. dr J. Biziela w Bydgoszcz

    Bydgoszcz, 85-168

  • Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich, Oddzial Hematologiczny

    Chorzów, 41-500

  • Malopolskie Centrum Medyczne s c

    Krakow, 30-510Komisja Bioctyczn

  • Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. Kopernika w Lodzi

    Lodz, 93-513

  • Instytut Hematologii i Transfuzjologii

    Warsaw, 02-776

  • Uniwersytecki Szpital Kliniczny im. J. Mikulicza-Radeckiego we Wroclawiu, PZOZ

    Wroclaw, 50-367

Other trials in Poland

Ukraine6 sites

  • Communal Nonprofit enterprise Cherkasy Regional Oncology Dispensary ofCherkasy Oblast Council,Regional Treatment and Diagnostic Hematological Center

    Cherkasy, 18009

  • Communal Non-profit Enterprise Regional Center of Oncology, Department of Hematology

    Kharkiv, 61070

  • 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, 03022

  • SI national Scientific Center of Radiation Medicine of NAMS of Ukraine, Dep. of Radiation Oncohematology and Stem Cell Transplantation Unit

    Kyiv, 03115

  • Andrii Novak Transcarpathian Regional Clinical Hospital, Department of Hematology

    Uzhhorod, 88018

  • Communal Institution O.F. Herbachevskyi Regional Clinical Hospital of Zhytomyr Regional Council Dept of Hematology with beds of Intensive Therapy

    Zhytomyr, 10002

Other trials in Ukraine

Netherlands5 sites

  • Universitair Medisch Centrum Groningen

    Groningen, 9713 GZ

  • Spaarne Gasthuis

    Hoofddorp, 2134 TM

  • Leiden University Medical Center

    Leiden, 2333 ZA

  • Erasmus MC

    Rotterdam, 3015 CE

  • Franciscus Vlietland

    Schiedam, 3118 JH

Other trials in Netherlands

South Korea5 sites

  • Gachon University Gil Medical Center

    Incheon, 21565

  • Seoul National University Hospital

    Seoul, 03080

  • Severance Hospital, Yonsei University Health System

    Seoul, 03722

  • Samsung Medical Center

    Seoul, 06351

  • The Catholic University of Korea, Seoul St. Mary's Hospital

    Seoul, 06591

Other trials in South Korea

Belgium4 sites

  • ZiekenhuisNetwerk Antwerpen (ZNA) Stuivenberg

    Antwerp, 2060

  • AZ Sint-Jan Brugge-Oostende AV

    Bruges, 8000

  • Institut Jules Bordet

    Brussels, 1000

  • CHU UCL Namur asbl- Mont Godinne

    Yvoir, 5530

Other trials in Belgium

Turkey (Türkiye)4 sites

  • Gazi Universitesi Tip Fakultesi, Besevler

    Ankara, 06500

  • Dokuz Eylul Universitesi Tip Fakultesi

    Izmir

  • Ondokuz Mayiz universitesi Tip Fakultesi

    Kurupelit, Samsun, 55139

  • Namik Kemal Universitesi Saglik Uyg. ve.Ars. Hastanesi

    Tekirdağ, 59030

Other trials in Turkey (Türkiye)

About this study

Official title: 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.

Being tested
Ibrutinib, Venetoclax, Placebo Oral tablet to match Venetoclax
Keywords
PCYC, MCL, Non-Hodgkin's Lymphoma, NHL, ibrutinib, venetoclax, Pharmacyclics
Medical subject headings
Lymphoma, Mantle-Cell, Lymphoma, Non-Hodgkin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IbrutinibDrug

    Administered orally once daily

  • VenetoclaxDrug

    Administered orally once daily

  • Placebo Oral tablet to match VenetoclaxDrug

    Administered orally once daily

Study groups in NCT03112174
Study groupRoleWhat they receive
Safety Run-inExperimentalParticipants 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.
Receives: Drug: Ibrutinib; Drug: Venetoclax
Randomization Phase: Ibrutinb + VenetoclaxExperimentalParticipants 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.
Receives: Drug: Ibrutinib; Drug: Venetoclax
Randomization Phase: Ibrutinib + PlaceboPlacebo comparatorParticipants 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.
Receives: Drug: Ibrutinib; Drug: Placebo Oral tablet to match Venetoclax
Treatment-naive Open-label ArmExperimentalParticipants are treated with ibrutinib 560 mg and venetoclax 400 mg, administered using the 5-week ramp-up schedule.
Receives: Drug: Ibrutinib; Drug: Venetoclax

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Tumor Lysis Syndrome (TLS) Events (Safety Run-in)

    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.

    Measured: After at least 3 months of treatment, with an overall median treatment duration of 20.0 months

  2. Number of Participants With Dose Limiting Toxicities (DLT) (Safety Run-in)

    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.

    Measured: After at least 3 months of treatment, with an overall median treatment duration of 20.0 months

  3. Number of Participants With Treatment Emergent Adverse Events (TEAEs) (Safety Run-in)

    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).

    Measured: From first dose of study drug until the end of treatment + 30 days, with an overall median treatment duration of 20.0 months

  4. Progression-free Survival (PFS) (Randomization Phase)

    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.

    Measured: For an overall median time on study of 61.34 months

  5. Complete Response (CR) Rate (Treatment-Naive Arm)

    CR rate is defined as the percentage of participants with a CR according to the Revised Response Criteria for Malignant Lymphoma (Cheson 2014).

    Measured: For an overall median time on study of 40.51 months

Secondary outcomes (27)

  1. Overall Survival (OS) (Safety Run-in)

    OS is defined as the time from the date of the first dose of study treatment to death from any cause.

    Measured: For an overall median time on study of 74.78 months

  2. Progression-free Survival (PFS) (Safety Run-in)

    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.

    Measured: For an overall median time on study of 74.78 months

  3. Duration of Response (DOR) (Safety Run-in)

    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.

    Measured: For an overall median time on study of 74.78 months

  4. Overall Response Rate (ORR) (Safety Run-in)

    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).

    Measured: For an overall median time on study of 74.78 months

  5. Percentage of Participants With a Complete Response (CR) (Randomization Phase)

    Complete response rate (CR) based on the best overall response per investigator assessment according to the Revised Response Criteria for Malignant Lymphoma (Cheson 2014).

    Measured: For an overall median time on study of 61.34 months

  6. Overall Response Rate (ORR) (Randomization Phase and Treatment-Naive 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).

    Measured: For an overall median time on study of 61.34 months (Randomization Phase) and 40.51 months (Treatment-Naïve arm)

  7. MRD-negative Remission Rate in Participants Who Achieve CR Per Investigator Assessment (Randomization Phase and Treatment-Naive 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.

    Measured: For an overall median time on study of 61.34 months (Randomization Phase) and 40.51 months (Treatment-Naïve arm)

  8. Overall Survival (OS) (Randomization Phase and Treatment-Naive 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.

    Measured: For an overall median time on study of 61.34 months (Randomization Phase) and 40.51 months (Treatment-Naïve arm)

  9. Duration of Response (DOR) (Randomization Phase and Treatment-Naive 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.

    Measured: For an overall median time on study of 61.34 months (Randomization Phase) and 40.51 months (Treatment-Naïve arm)

  10. Time to Next Treatment (TTNT) (Randomization Phase and Treatment-Naive 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).

    Measured: For an overall median time on study of 61.34 months (Randomization Phase) and 40.51 months (Treatment-Naïve arm)

  11. Number of Participants With TEAEs (Randomization Phase)

    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).

    Measured: From first dose of study drug until the end of treatment + 30 days, with an overall median treatment duration of 19.5 months

  12. Number of Participants With TLS TEAEs (Randomization Phase)

    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).

    Measured: From first dose of study drug until the end of treatment + 7 days, with an overall median treatment duration 19.5 months

  13. Steady-State Pharmacokinetics (PK) of Ibrutinib: Maximum Observed Plasma Concentration (Cmax) (Randomization Phase)

    Pre-dose concentrations were applied as 24-hour concentrations in order to calculate steady-state PK parameters.

    Measured: 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

  14. Steady-State PK of Ibrutinib: Time to Cmax (Tmax) (Randomization Phase)

    Pre-dose concentrations were applied as 24-hour concentrations in order to calculate steady-state PK parameters.

    Measured: 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

  15. 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)

    Pre-dose concentrations were applied as 24-hour concentrations in order to calculate steady-state PK parameters.

    Measured: 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

  16. Steady-State PK of Ibrutinib: Terminal Elimination Half-Life (t1/2,Term) (Randomization Phase)

    Pre-dose concentrations were applied as 24-hour concentrations in order to calculate steady-state PK parameters.

    Measured: 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

  17. Steady-State PK of Ibrutinib: Time of Last Measurable Concentration (Tlast) (Randomization Phase)

    Pre-dose concentrations were applied as 24-hour concentrations in order to calculate steady-state PK parameters.

    Measured: 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

  18. Steady-State PK of Ibrutinib: Area Under the Concentration-Time Curve From 0-24 Hours (AUC0-24) (Randomization Phase)

    Pre-dose concentrations were applied as 24-hour concentrations in order to calculate steady-state PK parameters.

    Measured: 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

  19. Steady-State PK of Ibrutinib: Terminal Elimination Rate Constant (λz) (Randomization Phase)

    Pre-dose concentrations were applied as 24-hour concentrations in order to calculate steady-state PK parameters.

    Measured: 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

  20. Steady-State PK of Ibrutinib: Apparent Total Clearance at Steady State (CLss/F) (Randomization Phase)

    Pre-dose concentrations were applied as 24-hour concentrations in order to calculate steady-state PK parameters.

    Measured: 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

  21. Steady-State PK of Venetoclax: Cmax (Randomization Phase)

    Pre-dose concentrations were applied as 24-hour concentrations in order to calculate steady-state PK parameters.

    Measured: 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

  22. Steady-State PK of Venetoclax: AUC0-24 (Randomization Phase)

    Pre-dose concentrations were applied as 24-hour concentrations in order to calculate steady-state PK parameters.

    Measured: 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

  23. Steady-State PK of Venetoclax: Time to Cmax (Tmax) (Randomization Phase)

    Pre-dose concentrations were applied as 24-hour concentrations in order to calculate steady-state PK parameters.

    Measured: 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

  24. Steady-State PK of Venetoclax: CLss/F (Randomization Phase)

    Pre-dose concentrations were applied as 24-hour concentrations in order to calculate steady-state PK parameters.

    Measured: 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

  25. Time to Worsening in Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Subscale of the Health-related Quality of Life (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.

    Measured: For an overall median time on study of 61.34 months (Randomization Phase)

  26. Duration of CR (Treatment-Naive Arm)

    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.

    Measured: For an overall median time on study of 40.51 months

  27. Progression-free Survival (PFS) (Treatment-Naive Arm)

    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.

    Measured: For an overall median time on study of 40.51 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Apr 2017
  2. Study start19 Jun 2017
  3. Primary completion26 Jun 2024
  4. Study completion27 Jun 2024

Resources

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
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
366 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03112174
Sponsor's protocol ID
PCYC-1143-CA
Other IDs
2017-000129-12, 2017
Acronym
SYMPATICO
Status last verified
Jul 2025
First submitted
4 Apr 2017
Last updated
22 Jul 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Wang M, Hoffmann MS, Wrobel T, Trneny M, Belada D, Demirken F, Panayiotidis P, Jurczak W, Zinzani PL, Keating MM, Yoon SS, Egyed M, Tam CS, Johnson NA, Szafer Glusman E, Lin J, Dean JP, Neuenburg JK, von Keudell G. First-line ibrutinib plus venetoclax for non-blastoid mantle cell lymphoma in patients >/=65 years or with TP53 mutations. Blood. 2026 Jul 1:blood.2025032833. doi: 10.1182/blood.2025032833. Online ahead of print.

    PubMed 42462092

  • 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.

    PubMed 39914418

  • 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.

    PubMed 34717692

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ibrutinib and Venetoclax in people with Mantle-Cell Lymphoma, run by Pharmacyclics LLC. at 120 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 13 inclusion and 25 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 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 120 sites in United States, Italy, Germany, France, Australia 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. Some participants in this study may receive a placebo. 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 22 Jul 2025). 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?

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). The study lists 5 primary outcomes in all. 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 NCT03112174, 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 Jul 2025.

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