Clinical trial • Phase III • Oncology
ZANUBRUTINIB for Splenic marginal zone lymphoma
Phase III trial of ZANUBRUTINIB for Splenic marginal zone lymphoma.
Overview
- Trial Therapeutic Area
- Oncology
- Trial Disease
- Splenic marginal zone lymphoma
- Trial Stage
- Phase III
- Drug Modality
- Small molecule | Monoclonal antibody
Key dates
- Initial CTIS Submission Date
- 15-12-2023
- First CTIS Authorization Date
- 24-04-2024
Trial design
Randomised, open-label, rituximab monotherapy (truxima 500 mg concentrate for solution for infusion; rituximab iv, dose reported as mg/m2 with max daily amount 375 mg/m2 per product information) compared with rituximab plus zanubrutinib (zanubrutinib oral; product information reports max daily dose 320 mg).-controlled Phase III trial in Italy, Spain, Austria and others.
- Randomised
- Yes
- Open Label
- Yes
- Comparator
- Rituximab monotherapy (Truxima 500 mg concentrate for solution for infusion; rituximab IV, dose reported as mg/m2 with max daily amount 375 mg/m2 per product information) compared with rituximab plus zanubrutinib (zanubrutinib oral; product information reports max daily dose 320 mg).
- Target Sample Size
- 90
- Trial Duration For Participant
- 1095
Eligibility
Recruits 90 No vulnerable population selected; only adults (Age ≥ 18 years). Ability to understand and willingness to sign a written informed consent required..
- Pregnancy Exclusion
- Pregnancy or breastfeeding.
- Vulnerable Population
- No vulnerable population selected; only adults (Age ≥ 18 years). Ability to understand and willingness to sign a written informed consent required.
Inclusion criteria
- {"criterion_text":"- Ability to understand and willingness to sign a written informed consent in accordance with ICH/GCP regulations before registration and prior to any trial-specific procedures."}
- {"criterion_text":"- Absolute neutrophil count (ANC) ≥ 1.0 x 109/L, platelet count ≥ 50 x 109/L, Hb > 7.5 g/dl. Values below such thresholds are allowed if attributable to the underlying lymphoma. Transfusions are allowed if clinically indicated during screening."}
- {"criterion_text":"- Adequate hepatic and renal function and coagulation parameters"}
- {"criterion_text":"- Patient able and willing to swallow trial drugs as whole tablet/capsule."}
- {"criterion_text":"- Female subjects who are of non-reproductive potential and female subjects of childbearing potential with a negative serum pregnancy test upon study entry."}
- {"criterion_text":"- Male and female subjects who agree to use highly effective methods of birth control during the period of therapy and for 12 months after the last dose of rituximab and 30 days after the last dose of zanubrutinib."}
- {"criterion_text":"- Confirmed diagnosis of SMZL, including Matutes immunophenotype score <3. Evaluation of the following features is desirable: absence of CD103, expression by flow cytometry, absence of Cyclin D1, BCL6, and CD10 expression by immunohistochemistry, and absence of the MYD88 L265P mutation. Patients with prominent splenomegaly and involvement of the splenic hilar and/or extra hilar lymph nodes are eligible."}
- {"criterion_text":"- Previously untreated disease. Patients with prior hepatitis C virus (HCV) infection who underwent HCV eradication and have persistent SMZL after 3 months post-eradication can be included."}
- {"criterion_text":"- Treatment needs according to the ESMO guideline criteria."}
- {"criterion_text":"- Measurable lesions"}
- {"criterion_text":"- Age ≥ 18 years."}
- {"criterion_text":"- European Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2."}
Exclusion criteria
- {"criterion_text":"- Previous splenectomy"}
- {"criterion_text":"- History of confirmed progressive multifocal leukoencephalopathy"}
- {"criterion_text":"- Concomitant diseases that require anticoagulant therapy with warfarin or phenprocoumon or other vitamin K antagonists and patients treated with dual anti-platelet therapy. Patients being treated with factor Xa inhibitors (eg, rivaroxaban, apixaban, edoxaban), direct thrombin inhibitors (e. dabigatran) low molecular weight heparin (LMWH), or single anti-platelet agents (eg. aspirin, clopidogrel) can be included but must be properly informed about the potential risk of bleeding"}
- {"criterion_text":"- Malabsorption syndrome or other condition that precludes the enteral route of administration"}
- {"criterion_text":"- Other sever acute or chronic medical or psychiatric condition or laboratory abnormalities which may increase the risk associates with trial participation and/or would make the patient inappropriate for enrolment into this trial."}
- {"criterion_text":"- Pregnancy or breastfeeding."}
- {"criterion_text":"- Concurrent participation in another therapeutic clinical trial."}
- {"criterion_text":"- Any uncontrolled active systemic infection requiring intravenous antimicrobial treatment, known human immunodeficiency virus (HIV) infection, active COronaVIrus Disease 19 (COVID-19) infection, presence of viral hepatitis B surface antigen (HBsAg) or viral hepatitis B core antibody (HBcAb), Presence of HCV antibody"}
- {"criterion_text":"- Active, uncontrolled autoimmune phenomenon"}
- {"criterion_text":"- Concomitant treatment with strong CYP3A inducers or inhibitors."}
- {"criterion_text":"- Any systemic therapy for SMZL."}
- {"criterion_text":"- Patients with central nervous system (CNS) involvement."}
- {"criterion_text":"- Prior malignancy (other than the disease under study) within the past 2 years, except for curatively treated basal or squamous skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast, or localized Gleason score ≤ 6 prostate cancer."}
- {"criterion_text":"- Clinically significant cardiovascular disease"}
- {"criterion_text":"- History of cerebrovascular accident or intracranial hemorrhage within 6 months before registration and known bleeding disorders (eg, von Willebrand’s disease or hemophilia)."}
Endpoints
Primary endpoints
- {"endpoint_text":"- Investigator-assessed PFS rate at 3 years according to the Lugano 2014 criteria","definition_or_measurement_approach":"Investigator-assessed progression-free survival rate at 3 years measured according to the Lugano 2014 criteria."}
Secondary endpoints
- {"endpoint_text":"- Investigator-assessed complete remission rates achieved at 12 and 24 months of treatment, assessed according to the Lugano 2014 criteria.","definition_or_measurement_approach":"Complete remission rates at 12 and 24 months assessed by investigator per Lugano 2014 criteria."}
- {"endpoint_text":"- Investigator-assessed best response achieved at any time during the treatment period (24 months) assessed according to the Lugano 2014 criteria","definition_or_measurement_approach":"Best response during 24-month treatment period assessed by investigator per Lugano 2014 criteria."}
- {"endpoint_text":"- Investigator-assessed complete remission rates achieved at 12 and 24 months of treatment, assessed according to the Matutes criteria","definition_or_measurement_approach":"Complete remission rates at 12 and 24 months assessed by investigator per Matutes criteria."}
- {"endpoint_text":"- Investigator-assessed best response achieved at any time during the treatment period (24 months) assessed according to the Matutes criteria","definition_or_measurement_approach":"Best response during 24-month treatment period assessed by investigator per Matutes criteria."}
- {"endpoint_text":"- Investigator-assessed Time to next anti-lymphoma treatment (TTNT) according to the Lugano 2014 criteria","definition_or_measurement_approach":"Time from randomization to start of next anti-lymphoma therapy, assessed by investigator per Lugano 2014 criteria."}
- {"endpoint_text":"- Investigator-assessed duration of response according to the Lugano 2014 criteria","definition_or_measurement_approach":"Duration of response (DoR) measured per investigator using Lugano 2014 criteria."}
- {"endpoint_text":"- Overall Survival according to the Lugano 2014 criteria","definition_or_measurement_approach":"Overall survival (OS) measured from randomization to death from any cause; assessments referenced to Lugano 2014 criteria for disease status."}
- {"endpoint_text":"- Analysis of type and severity of adverse events (AEs) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0","definition_or_measurement_approach":"Adverse events coded and graded according to NCI-CTCAE v5.0; analysis of type and severity by investigator."}
Recruitment
- Planned Sample Size
- 90
- Recruitment Window Months
- 60
- Consent Approach
- Written informed consent required from participants able to understand and willing to sign prior to any trial procedures. Participants must be adults (Age ≥ 18). Subject information and consent forms and patient-facing materials are provided in country-specific languages as per document list (examples include Italian, Spanish, French, Swedish, Norwegian, Danish and English versions listed).
Geography
- Total Number Of Sites
- 42
- Total Number Of Participants
- 90
Italy
- Earliest CTIS Part Ii Submission Date
- 22-03-2024
- Latest Decision Or Authorization Date
- 27-01-2026
- Processing Time Days
- 676
- Number Of Sites
- 16
- Number Of Participants
- 35
Sites
- Site Name
- Grande Ospedale Metropolitano Bianchi Melacrino Morelli
- Department Name
- Hematology
- Contact Person Name
- Caterina Cecilia Stelitano
- Contact Person Email
- caterina.stelitano@ospedalerc.it
- Site Name
- Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
- Department Name
- Hematology
- Contact Person Name
- Michele Merli
- Contact Person Email
- michele.merli@policlinico.mi.it
- Site Name
- Azienda Unita Sanitaria Locale Della Romagna
- Department Name
- Hematology
- Contact Person Name
- Monica Tani
- Contact Person Email
- monica.tani@auslromagna.it
- Site Name
- Azienda Ospedaliero-Universitaria Maggiore Della Carita
- Department Name
- Hematology
- Contact Person Name
- Gloria Margiotta Casaluci
- Contact Person Email
- gloria.margiotta@med.uniupo.it
- Site Name
- ASST Grande Ospedale Metropolitano Niguarda
- Department Name
- Hematology
- Contact Person Name
- Anna Maria Frustaci
- Contact Person Email
- annamaria.frustaci@ospedaleniguarda.it
- Site Name
- Azienda Ospedaliera Ospedale Di Circolo E Fondazione Macchi
- Department Name
- Hematology
- Contact Person Name
- Marta Coscia
- Contact Person Email
- marta.coscia@asst-settelaghi.it
- Site Name
- Ospedale San Raffaele S.r.l.
- Department Name
- Oncology
- Contact Person Name
- Lydia Scarfò
- Contact Person Email
- scarfo.lydia@hsr.it
- Site Name
- Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
- Department Name
- Hematology
- Contact Person Name
- Antonella Anastasia
- Contact Person Email
- antonella.anastasia@asst-spedalicivili.it
- Site Name
- Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello
- Department Name
- Oncohematology
- Contact Person Name
- Caterina Patti
- Contact Person Email
- k.patti@villasofia.it
- Site Name
- IRCCS Azienda Ospedaliero Universitaria di Bologna - Policlinico S. Orsola-Malpighi
- Department Name
- Hematology
- Contact Person Name
- Pier Luigi Zinzani
- Contact Person Email
- pierluigi.zinzani@unibo.it
- Site Name
- Azienda USL IRCCS Di Reggio Emilia
- Department Name
- Hematology
- Contact Person Name
- Stefano Luminari
- Contact Person Email
- stefano.luminari@ausl.re.it
- Site Name
- Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.
- Department Name
- Hematology
- Contact Person Name
- Pietro Rossi
- Contact Person Email
- pietro.rossi@irst.emr.it
- Site Name
- Azienda Ospedaliero-Universitaria Policlinico G. Rodolico-San Marco Di Catania
- Department Name
- Oncology
- Contact Person Name
- Annalisa Chiarenza
- Contact Person Email
- annalisa.chiarenza@gmail.com
- Site Name
- Istituto Tumori Bari Giovanni Paolo II
- Department Name
- Hematology
- Contact Person Name
- Carla Minoia
- Contact Person Email
- c.minoia@oncologico.bari.it
- Site Name
- Azienda Ospedaliera Universitaria Senese
- Department Name
- Hematology
- Contact Person Name
- Emanuele Cencini
- Contact Person Email
- emanuele.cencini@ao-siena.toscana.it
- Site Name
- Fondazione IRCCS Policlinico San Matteo
- Department Name
- Hematology
- Contact Person Name
- Luca Arcaini
- Contact Person Email
- l.arcaini@smatteo.pv.it
Spain
- Earliest CTIS Part Ii Submission Date
- 16-01-2024
- Latest Decision Or Authorization Date
- 12-12-2025
- Processing Time Days
- 696
- Number Of Sites
- 15
- Number Of Participants
- 25
Sites
- Site Name
- Hospital Universitario De Cruces
- Department Name
- Hematology
- Contact Person Name
- Xabier Martin Martitegui
- Contact Person Email
- xabier.martinmartitegui@osakidetza.eus
- Site Name
- Hospital Clinic De Barcelona
- Department Name
- Hematology
- Contact Person Name
- Juan Gonzalo Correa Saldarriaga
- Contact Person Email
- jgonzalo@clinic.cat
- Site Name
- University Clinical Hospital Virgen De La Arrixaca
- Department Name
- Hematology
- Contact Person Name
- Almudena Cascales
- Contact Person Email
- almudena.cascales@gmail.com
- Site Name
- Hospital Universitari Vall D Hebron
- Department Name
- Hematology
- Contact Person Name
- Gloria Iacoboni
- Contact Person Email
- giacoboni@vhio.net
- Site Name
- Hospital Universitario 12 De Octubre
- Department Name
- Hematology
- Contact Person Name
- Ana Jiménez Ubieto
- Contact Person Email
- anitiju@hotmail.com
- Site Name
- Hospital Universitario De Salamanca
- Department Name
- Hematology
- Contact Person Name
- Norma Gutiérrez
- Contact Person Email
- normagu@usal.es
- Site Name
- Hospital Unviersitario Miguel Servet
- Department Name
- Hematology
- Contact Person Name
- Araceli Rubio Martinez
- Contact Person Email
- arubiom@salud.aragon.es
- Site Name
- Clinica Universidad De Navarra (Madrid)
- Department Name
- Hematology
- Contact Person Name
- Carlos Grande Garcia
- Contact Person Email
- cgrandeg@unav.es
- Site Name
- Hospital Clinico Universitario De Valencia
- Department Name
- Hematology
- Contact Person Name
- Ana Saus Carreres
- Contact Person Email
- saus_ana@gva.es
- Site Name
- Hospital Universitario Donostia
- Department Name
- Hematology
- Contact Person Name
- Izaskun Zeberio Etxetxipia
- Contact Person Email
- IZASIZASKUN.ZEBERIOETXETXIPIA@osakidetza.eus
- Site Name
- Hospital Del Mar
- Department Name
- Hematology
- Contact Person Name
- Blanca Sánchez González
- Contact Person Email
- 97894@hospitaldelmar.cat
- Site Name
- Hospital Universitario Ramon Y Cajal
- Department Name
- Hematology
- Contact Person Name
- Francisco Javier Lopez
- Contact Person Email
- jljimenez@salud.madrid.org
- Site Name
- Hospital General Universitario Gregorio Maranon
- Department Name
- Hematology
- Contact Person Name
- Mariana Bastos Oreiro
- Contact Person Email
- bastosmariana@yahoo.com
- Site Name
- Clinica Universidad De Navarra (Pamplona)
- Department Name
- Hematology
- Contact Person Name
- Carlos Grande Garcia
- Contact Person Email
- cgrandeg@unav.es
- Site Name
- Institut Catala D'oncologia
- Department Name
- Hematology
- Contact Person Name
- Eva Domingo Domenech
- Contact Person Email
- edomingo@iconcologia.net
Austria
- Earliest CTIS Part Ii Submission Date
- 15-03-2024
- Latest Decision Or Authorization Date
- 15-12-2025
- Processing Time Days
- 654
- Number Of Sites
- 1
- Number Of Participants
- 10
Sites
- Site Name
- Medical University Of Vienna
- Department Name
- Department of Medicine I, Division of Oncology
- Contact Person Name
- Markus Raderer
- Contact Person Email
- markus.raderer@meduniwien.ac.at
Denmark
- Earliest CTIS Part Ii Submission Date
- 30-07-2024
- Latest Decision Or Authorization Date
- 10-12-2025
- Processing Time Days
- 498
- Number Of Sites
- 1
- Number Of Participants
- 2
Sites
- Site Name
- Aarhus University Hospital
- Department Name
- Hematology
- Contact Person Name
- Ahmed Ludvigsen Al-Mashhadi
- Contact Person Email
- ahmhus@rm.dk
France
- Earliest CTIS Part Ii Submission Date
- 04-04-2024
- Latest Decision Or Authorization Date
- 15-12-2025
- Processing Time Days
- 620
- Number Of Sites
- 5
- Number Of Participants
- 14
Sites
- Site Name
- Centre Hospitalier Universitaire Grenoble Alpes
- Department Name
- Hematology
- Contact Person Name
- Sylvain Carras
- Contact Person Email
- scarras@chu-grenoble.fr
- Site Name
- Institut Bergonie
- Department Name
- Hematology
- Contact Person Name
- Fontanet Bijou
- Contact Person Email
- f.bijou@bordeaux.unicancer.fr
- Site Name
- Hopital Saint Louis
- Department Name
- Hematology
- Contact Person Name
- Catherine Thieblemont
- Contact Person Email
- catherine.thieblemont@aphp.fr
- Site Name
- CHRU De Nancy
- Department Name
- Hematology
- Contact Person Name
- Pierre Feugier
- Contact Person Email
- p.feugier@chru-nancy.fr
- Site Name
- Centre Hospitalier Lyon Sud
- Department Name
- Hematology
- Contact Person Name
- Pierre Sesques
- Contact Person Email
- pierre.sesques@chu-lyon.fr
Norway
- Earliest CTIS Part Ii Submission Date
- 12-07-2024
- Latest Decision Or Authorization Date
- 10-12-2025
- Processing Time Days
- 516
- Number Of Sites
- 2
- Number Of Participants
- 2
Sites
- Site Name
- Oslo University Hospital HF
- Department Name
- Oncology
- Contact Person Name
- Marianne Brodtkorb
- Contact Person Email
- meide@ous-hf.no
- Site Name
- St. Olavs Hospital HF
- Department Name
- Oncology
- Contact Person Name
- Karin Fahl Wader
- Contact Person Email
- post@stolav.no
Sweden
- Earliest CTIS Part Ii Submission Date
- 29-07-2025
- Latest Decision Or Authorization Date
- 15-12-2025
- Processing Time Days
- 139
- Number Of Sites
- 2
- Number Of Participants
- 2
Sites
- Site Name
- Karolinska University Hospital
- Department Name
- Hematology
- Contact Person Name
- Bjorn Wahlin
- Contact Person Email
- bjorn.wahlin@ki.se
- Site Name
- Universitetssjukhus Skane
- Department Name
- Oncology
- Contact Person Name
- Mats Jerkeman
- Contact Person Email
- mats.jerkeman@med.lu.se
Sponsor
Primary sponsor
- Full Name
- Association International Extranodal Lymphoma Study Group
- Organisation Type
- Laboratory/Research/Testing facility
- Country Of Registered Address
- Switzerland
Third parties
- {"country":"Netherlands","full_name":"Siron bv","duties_or_roles":"1","organisation_type":"Industry"}
Investigational products
- Investigational Product Name
- Zanubrutinib
- Active Substance
- ZANUBRUTINIB
- Modality
- Small molecule
- Routes Of Administration
- ORAL
- Route
- ORAL
- Maximum Dose
- 320 mg (max daily amount as reported)
- Investigational Product Name
- Truxima 500 mg concentrate for solution for infusion
- Active Substance
- RITUXIMAB
- Modality
- Monoclonal antibody
- Routes Of Administration
- INTRAVENOUS
- Route
- INTRAVENOUS
- Authorisation Status
- Authorised (marketing authorisation referenced: EU/1/16/1167/001)
- Maximum Dose
- 375 mg/m2 (as reported)
- Combination Treatment
- Yes
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