Splenic Marginal Zone LymphomaPhase 3RITZNCT05735834
Comparison Between Rituximab Plus Zanubrutinib Versus Rituximab Monotherapy in Untreated SMZL Patients
A Phase 3 study testing Rituximab and Zanubrutinib in people with Splenic Marginal Zone Lymphoma, run by International Extranodal Lymphoma Study Group (IELSG) at 49 sites in 8 countries.
Trial summary
The goal of this clinical trial is to compare the efficacy and tolerability of the combination of two medicinal products, rituximab, and zanubrutinib, compared to rituximab monotherapy in patients with Splenic Marginal Zone Lymphoma (SMZL), previously untreated and who need systemic treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Splenic Marginal Zone Lymphoma
- What is being tested?
- Rituximab and Zanubrutinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 122 participants
- Where
- 49 sitesin 8 countries
- Study dates
- 21 May 2024to May 2029
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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
- 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.
- 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
- 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.
- Treatment needs according to the ESMO guideline criteria
- Measurable lesions
- Age ≥ 18 years.
Show all 10Show fewer
- European Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
- 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.
- Adequate hepatic and renal function and coagulation parameters
- Patient able and willing to swallow trial drugs as whole tablet/capsule
Who cannot join
- Previous splenectomy.
- Any systemic therapy for SMZL.
- Patients with central nervous system (CNS) involvement.
- 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.
- Clinically significant cardiovascular disease
- History of cerebrovascular accident or intracranial hemorrhage within 6 months before registration and known bleeding disorders (eg, von Willebrand's disease or hemophilia).
Show all 19Show fewer
- History of confirmed progressive multifocal leukoencephalopathy (PML).
- 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.
- Malabsorption syndrome or other condition that precludes the enteral route of administration.
- Any uncontrolled active systemic infection requiring intravenous antimicrobial treatment.
- Known human immunodeficiency virus (HIV) infection.
- Active COronaVIrus Disease 19 (COVID-19) infection or non-compliance with the prevailing hygiene measures regarding the COVID-19 pandemic.
- Active chronic hepatitis C or hepatitis B virus infection
- Active, uncontrolled autoimmune phenomenon (autoimmune hemolytic anemia or immune. thrombocytopenia) requiring steroid therapy with > 20 mg daily of prednisone dose or equivalent.
- Known hypersensitivity to trial drugs or any component of the trial drugs.
- Concomitant treatment with strong CYP3A inducers or inhibitors
- Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and/or would make the patient inappropriate for enrolment into this trial.
- Pregnancy or breastfeeding.
- Concurrent participation in another therapeutic clinical trial.
Trial locations and contacts
49 sites in 8 countries.
49 sites in 8 countries
Italy15 sites
IRCCS Istituto Tumori Giovanni Paolo II
Bari, 70124
IRCCS AOU di Bologna
Bologna, 40138
ASST Spedali Civili di Brescia
Brescia, 25123
A.O.U. Policlinico G. Rodolico-S. Marco
Catania, 95123
IRCCS IRST Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori"
Meldola, 47014
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Milan, 20122
IRCCS Ospedale San Raffaele
Milan, 20132
ASST Grande Ospedale Metropolitano Niguarda
Milan, 20162
Azienda Ospedaliero Universitaria Maggiore della Carità
Novara, 28100
Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello
Palermo, 90146
IRCCS Policlinico San Matteo
Pavia
Ospedale Santa Maria delle Croci
Ravenna, 48121
USL-IRCCS of Reggio Emilia, Arcispedale Santa Maria Nuova
Reggio Emilia, 42123
Policlinico Santa Maria alle Scotte
Siena, 53100
Ospedale di Circolo e Fondazione Macchi - ASST dei Sette Laghi
Varese, 21100
Spain15 sites
Hospedal Clinic de Barcelona
Barcelona
Hospital del Mar
Barcelona
Hospital Vall d'Hebron
Barcelona
Istitut Català d'Oncologia, Hospital Duran i Reynals
Barcelona
Hospital Universitario Cruces
Bilbao
Hospital Virgen Arrixaca
El Palmar
Clinica Universidad de Navarra
Madrid
Hospital 12 De Octubre
Madrid
Hospital Gregorio Marañón
Madrid
Hospital Ramon y Cajal
Madrid
Clinica Universidad de Navarra
Pamplona
Hospital De Salamanca
Salamanca
Hospital De Donostia
San Sebastián
Hospital Clinico De Valencia
Valencia
Hospital Universitario Miguel Servet
Zaragoza
United Kingdom9 sites
University Hospitals Dorset
Bournemouth, BH7 7DW
University Hospital of Wales
Cardiff, CF14 4XW
Hospital Beatson West of Scotland Cancer Centre
Glasgow, G12 0YN
Clatterbridge Cancer Centre
Liverpool, L7 8YA
University College London Hospitals
London, NW1 2PG
Guy's Hospital - Guy's and St. Thomas' NHS Foundation Trust
London, SE1 9RT
The Christie
Manchester, M20 4BX
Churchill Hospital
Oxford, OX3 7LE
The Royal Marsden NHS Foundation Trust
Sutton, SM2 5PT
France5 sites
Institut Bergonié
Bordeaux, 33076
CHU de Grenoble
Grenoble, 38043
Hôpital Saint Louis
Paris, 75475
Hôpital Lyon-Sud
Pierre-Bénite, 69495
CHRU Nancy Brabois
Vandœuvre-lès-Nancy, 54511
Switzerland2 sites
Oncology Institute of Southern Switzerland
Bellinzona, 6500
INSELSPITAL, Bern University Hospital
Bern, 3010
About this study
Official title: Phase 3, Interventional, Multicentre, Open-label, Randomized Study Comparing Rituximab Plus Zanubrutinib to Rituximab Monotherapy in Previously Untreated, Symptomatic Splenic Marginal Zone Lymphoma (RITZ)
The goal of this clinical trial is to compare the efficacy and tolerability of the combination of two medicinal products, rituximab, and zanubrutinib, compared to rituximab monotherapy in patients with Splenic Marginal Zone Lymphoma (SMZL), previously untreated and who need systemic treatment.
The main questions it aims to answer are:
Read more
- Is the combination rituximab and zanubrutinib a more effective therapy than rituximab monotherapy?
- Is the combination therapy, rituximab and zanubrutinib, well tolerated?
Study participants will be put into one of the two treatment groups (rituximab and zanubrutinib or rituximab alone) for a maximum of two years and will undergo regular visits until three years from treatment start.
Read the detailed description
Phase III, interventional, multicenter, open label, randomized study to evaluate whether treatment with zanubrutinib in combination with rituximab will result in an improvement in Progression Free Survival (PFS) compared to treatment with rituximab in patients with previously untreated splenic marginal zone lymphoma (SMZL).
Approximately 120 subjects will be randomized in a 1:1 ratio to receive zanubrutinib and rituximab (Treatment Arm A) or rituximab (Treatment Arm B). The study will include a Screening Phase, a Treatment Phase, and a Follow-Up Phase.
Subjects with investigator-confirmed progressive disease (PD) according to the Lugano 2014 criteria or unacceptable toxicity, or investigator/subject decision must discontinue study treatment.
Patients who complete the treatment and patients who will discontinue treatment for any reason will enter the Follow-up Phase.
The Response Follow-up Phase will occur for subjects who complete the treatment or discontinue for reasons other than disease progression and will include efficacy assessments every 24 weeks until investigator-assessed disease progression.
Subjects with PD during the Response Follow-up Phase will continue to be followed in the Survival Follow-up Phase.
An Independent Data Monitoring Committee (IDMC) will be responsible for independent review of the interim safety analysis on the first 20 enrolled patients in the experimental arm.
- Conditions
- Splenic Marginal Zone Lymphoma
- Being tested
- Rituximab, Zanubrutinib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabDrug
Also called Truxima
Truxima concentrate for solution for infusion 500 mg/50 ml
ZanubrutinibDrug
Also called Brukinsa
Zanubrutinib 80 mg hard capsules
| Study group | Role | What they receive |
|---|---|---|
| Arm A - Rituximab + Zanubrutinib | Experimental | Zanubrutinib (160 mg BID orally continuous dosing) is administered for 12 cycles of 28 days each. After cycle 12:
1. Patients in Complete Response (CR) will stop treatment and enter the follow-up phase.
2. Patients in partial response (PR) will continue zanubrutinib treatment (160 mg BID orally continuous dosing) for 12 additional cycles of 28 days each for a total of 24 cycles.
3. Patients in stable disease (SD) or progressive disease (PD) will stop treatment and will enter the follow-up phase.
Rituximab is infused at the dose of 375 mg/m2 iv on days 1, 8, 15, and 22 of cycle 1 (28 days per cycle), then on day 1 of cycles 3, 6, 9, and 12 (28 days per cycle). After cycle 12:
1. Patients in CR will stop treatment and enter the follow-up phase.
2. Patients in PR will go on with rituximab 375 mg/m2 IV on day 1 of cycles 15, 18, 21, and 24 (28 days per cycle).
3. Patients in SD or PD will discontinue treatment and will enter the follow-up phase. Receives: Drug: Rituximab; Drug: Zanubrutinib |
| Arm B - Rituximab | Active comparator | Rituximab is infused at the dose of 375 mg/m2 iv on days 1, 8, 15, and 22 of cycle 1 (28 days per cycle), then on day 1 of cycles 3, 6, 9, and 12 (28 days per cycle). After cycle 12:
1. Patients in CR will stop treatment and enter the follow-up phase.
2. Patients in PR will go on with rituximab 375 mg/m2 iv on day 1 of cycles 15, 18, 21, and 24 (28 days per cycle).
3. Patients in SD or PD will discontinue treatment and will enter the follow-up phase Receives: Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival (PFS) rate at 3 years
PFS is defined as the time from the date of randomization until progression (assessed by the investigator per Lugano 2014 criteria) or death from any cause, whichever occurs first
Measured: From the date of randomization to the date of progression or the date of death from any cause until 3 years after randomization
Secondary outcomes (8)
Complete remission rates - Lugano 2014 criteria
Investigator-assessed complete remission rates achieved at 12 and 24 months of treatment, assessed according to the Lugano 2014 criteria
Measured: At 12 and 24 months after treatment start
Best response
Investigator-assessed best response achieved at any time during the treatment period (24 months) assessed according to the Lugano 2014 criteria
Measured: From date of treatment start until 24 months after treatment start
Complete remission rates - Matutes criteria
Investigator-assessed complete remission rates achieved at 12 and 24 months of treatment, assessed according to the Matutes criteria
Measured: At 12 and 24 months after treatment start
Best response - Matutes criteria
Investigator-assessed best response achieved at any time during the treatment period (24 months) assessed according to the Matutes criteria
Measured: From date of treatment start until 24 months after treatment start
Time to next anti-lymphoma treatment (TTNT)
Investigator-assessed time to next anti-lymphoma treatment (TTNT) according to the Lugano 2014 criteria. TTNT is defined as time from the end of treatment until the start of the next therapy
Measured: From the end of treatment to the start of the next anti-lymphoma therapy until 3 years after randomization
Duration of response (DoR)
Investigator-assessed DoR according to the Lugano 2014 criteria
Measured: From the time when criteria for response (ie, CR or PR) are met to the first documentation of relapse or progression until 3 years from randomization
Overall Survival (OS)
OS according to the Lugano 2014 criteria. OS is defined as the time from random assignment until death as a result of any cause
Measured: From the time of randomization until death as a result of any cause until 3 years from randomization
Treatment Emergent Adverse Events (AEs)
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
Measured: From the time of ICF signature until 28 days after treatment discontinuation or until resolution of all treatment-related AEs, whichever occurs later, or starting of a new anti-neoplastic treatment up to 3 years from randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2023
- Study start21 May 2024
- Primary completionMay 2029 (estimated)
- Study completionMay 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Splenic Marginal Zone LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- None (open label)
- Enrolment
- 122 participants (actual)
Sponsor and investigators
- Lead sponsor
- International Extranodal Lymphoma Study Group (IELSG)
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Davide Rossi, MD, Study chair, Oncology Institute of Southern Switzerland - Bellinzona (Switzerland)Emanuele Zucca, MD, Study chair, International Extranodal Lymphoma Study Group (IELSG) - Bellinzona (Switzerland)Luca Arcaini, MD, Study chair, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05735834
- Sponsor's protocol ID
- IELSG48
- Other IDs
- 2023-503755-10-00, 2023
- Acronym
- RITZ
- Status last verified
- Jul 2026
- First submitted
- 9 Feb 2023
- Last updated
- 22 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Sharp J, Shana'ah AY, Voorhees TJ, Bond DA, Sawalha Y, Sigmund A, Hanel W, Sehgal L, Alinari L, Baiocchi R, Maddocks K, Jones D, Christian B, Epperla N. Resistance Mechanism for Zanubrutinib in Marginal Zone Lymphoma. J Natl Compr Canc Netw. 2025 Jun 23;23(7):e257045. doi: 10.6004/jnccn.2025.7045.
PubMed 40550489
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 3, Interventional, Multicentre, Open-label, Randomized Study Comparing Rituximab Plus Zanubrutinib to Rituximab Monotherapy in Previously Untreated, Symptomatic Splenic Marginal Zone Lymphoma (RITZ)
- ClinicalTrials.gov ID
- NCT05735834
- Acronym / sponsor ID
- RITZ / IELSG48
- Conditions
- Splenic Marginal Zone Lymphoma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 122 participants (actual)
- Lead sponsor
- International Extranodal Lymphoma Study Group (IELSG)University, hospital or other
- Study start
- 21 May 2024 (actual)
- Primary completion
- May 2029 (estimated)
- Study completion
- May 2029 (estimated)
- First posted
- 21 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to compare the efficacy and tolerability of the combination of two medicinal products, rituximab, and zanubrutinib, compared to rituximab monotherapy in patients with Splenic Marginal Zone Lymphoma (SMZL), previously untreated and who need systemic treatment.
The main questions it aims to answer are:
- Is the combination rituximab and zanubrutinib a more effective therapy than rituximab monotherapy?
- Is the combination therapy, rituximab and zanubrutinib, well tolerated?
Study participants will be put into one of the two treatment groups (rituximab and zanubrutinib or rituximab alone) for a maximum of two years and will undergo regular visits until three years from treatment start.
Detailed description
Phase III, interventional, multicenter, open label, randomized study to evaluate whether treatment with zanubrutinib in combination with rituximab will result in an improvement in Progression Free Survival (PFS) compared to treatment with rituximab in patients with previously untreated splenic marginal zone lymphoma (SMZL).
Approximately 120 subjects will be randomized in a 1:1 ratio to receive zanubrutinib and rituximab (Treatment Arm A) or rituximab (Treatment Arm B). The study will include a Screening Phase, a Treatment Phase, and a Follow-Up Phase.
Subjects with investigator-confirmed progressive disease (PD) according to the Lugano 2014 criteria or unacceptable toxicity, or investigator/subject decision must discontinue study treatment.
Patients who complete the treatment and patients who will discontinue treatment for any reason will enter the Follow-up Phase.
The Response Follow-up Phase will occur for subjects who complete the treatment or discontinue for reasons other than disease progression and will include efficacy assessments every 24 weeks until investigator-assessed disease progression.
Subjects with PD during the Response Follow-up Phase will continue to be followed in the Survival Follow-up Phase.
An Independent Data Monitoring Committee (IDMC) will be responsible for independent review of the interim safety analysis on the first 20 enrolled patients in the experimental arm.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A - Rituximab + Zanubrutinib | Experimental | Drug: Rituximab, Drug: ZanubrutinibZanubrutinib (160 mg BID orally continuous dosing) is administered for 12 cycles of 28 days each. After cycle 12: 1. Patients in Complete Response (CR) will stop treatment and enter the follow-up phase. 2. Patients in partial response (PR) will continue zanubrutinib treatment (160 mg BID orally continuous dosing) for 12 additional cycles of 28 days each for a total of 24 cycles. 3. Patients in stable disease (SD) or progressive disease (PD) will stop treatment and will enter the follow-up phase. Rituximab is infused at the dose of 375 mg/m2 iv on days 1, 8, 15, and 22 of cycle 1 (28 days per cycle), then on day 1 of cycles 3, 6, 9, and 12 (28 days per cycle). After cycle 12: 1. Patients in CR will stop treatment and enter the follow-up phase. 2. Patients in PR will go on with rituximab 375 mg/m2 IV on day 1 of cycles 15, 18, 21, and 24 (28 days per cycle). 3. Patients in SD or PD will discontinue treatment and will enter the follow-up phase. |
| Arm B - Rituximab | Active comparator | Drug: RituximabRituximab is infused at the dose of 375 mg/m2 iv on days 1, 8, 15, and 22 of cycle 1 (28 days per cycle), then on day 1 of cycles 3, 6, 9, and 12 (28 days per cycle). After cycle 12: 1. Patients in CR will stop treatment and enter the follow-up phase. 2. Patients in PR will go on with rituximab 375 mg/m2 iv on day 1 of cycles 15, 18, 21, and 24 (28 days per cycle). 3. Patients in SD or PD will discontinue treatment and will enter the follow-up phase |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
- 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
- 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.
- Treatment needs according to the ESMO guideline criteria
- Measurable lesions
Key exclusion criteria (19 listed)
- Previous splenectomy.
- Any systemic therapy for SMZL.
- Patients with central nervous system (CNS) involvement.
- 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.
- Clinically significant cardiovascular disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RituximabAlso: TruximaTruxima concentrate for solution for infusion 500 mg/50 ml | Drug | Arm A - Rituximab + Zanubrutinib, Arm B - Rituximab |
| ZanubrutinibAlso: BrukinsaZanubrutinib 80 mg hard capsules | Drug | Arm A - Rituximab + Zanubrutinib |
Primary outcome
Progression Free Survival (PFS) rate at 3 years
Time frame: From the date of randomization to the date of progression or the date of death from any cause until 3 years after randomization
PFS is defined as the time from the date of randomization until progression (assessed by the investigator per Lugano 2014 criteria) or death from any cause, whichever occurs first
8 secondary outcomes
Complete remission rates - Lugano 2014 criteria
Time frame: At 12 and 24 months after treatment start
Best response
Time frame: From date of treatment start until 24 months after treatment start
Complete remission rates - Matutes criteria
Time frame: At 12 and 24 months after treatment start
Best response - Matutes criteria
Time frame: From date of treatment start until 24 months after treatment start
Time to next anti-lymphoma treatment (TTNT)
Time frame: From the end of treatment to the start of the next anti-lymphoma therapy until 3 years after randomization
Duration of response (DoR)
Time frame: From the time when criteria for response (ie, CR or PR) are met to the first documentation of relapse or progression until 3 years from randomization
Overall Survival (OS)
Time frame: From the time of randomization until death as a result of any cause until 3 years from randomization
Treatment Emergent Adverse Events (AEs)
Time frame: From the time of ICF signature until 28 days after treatment discontinuation or until resolution of all treatment-related AEs, whichever occurs later, or starting of a new anti-neoplastic treatment up to 3 years from randomization
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2026.
- Derived from this study: PubMed 40550489Sharp J, Shana'ah AY, Voorhees TJ, Bond DA, Sawalha Y, Sigmund A, Hanel W, Sehgal L, Alinari L, Baiocchi R, Maddocks K, Jones D, Christian B, Epperla N. Resistance Mechanism for Zanubrutinib in Marginal Zone Lymphoma. J Natl Compr Canc Netw. 2025 Jun 23;23(7):e257045. doi: 10.6004/jnccn.2025.7045.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Davide Rossi, MD study chair
Oncology Institute of Southern Switzerland - Bellinzona (Switzerland)
Emanuele Zucca, MD study chair
International Extranodal Lymphoma Study Group (IELSG) - Bellinzona (Switzerland)
Luca Arcaini, MD study chair
Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
49 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Rituximab and Zanubrutinib in people with Splenic Marginal Zone Lymphoma, run by International Extranodal Lymphoma Study Group (IELSG) at 49 sites in 8 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 10 inclusion and 19 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: under way, not looking for participants, as of the sponsor's last update on 22 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 49 sites in Italy, Spain, United Kingdom, France, Switzerland and 3 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. 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?
This study is still under way. Results are not available in the source record yet.
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?
Progression Free Survival (PFS) rate at 3 years (time frame: From the date of randomization to the date of progression or the date of death from any cause until 3 years after randomization). 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 NCT05735834, which also lists 1 linked publication.
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 2026.