Waldenström's Macroglobulinemia (WM)NCT06441214
Retrospective-prospective Study to Evaluate Treatment Management and Outcomes of Patients With Waldenström's Macroglobulinemia (WM) Treated in Italy According to the Zanubrutinib (Brukinsa®) Compassionate Use Program (CUP) and in Common Practice Following Commercial Approval.
An observational study of Waldenström's Macroglobulinemia (WM), run by Fondazione Italiana Linfomi - ETS at 23 sites in Italy.
Trial summary
This is a non-interventional, observational, retrospective and prospective multicenter Italian study, to describe treatment management and outcomes of Waldenström's Macroglobulinemia (WM) patients treated according to the Italian Compassionate Use Program (CUP) and receiving zanubrutinib following its commercial… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Waldenström's Macroglobulinemia (WM)
- What is being tested?
- Zanubrutinib
- How many people
- 212 participants
- Where
- 23 sitesItaly
- Study dates
- 13 Dec 2024to Dec 2026
- Phase
- Observational
- 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
Study population: Patients with Waldenström's Macroglobulinemia (WM) treated in Italy according to the Zanubrutinib (Brukinsa®) compassionate use program (CUP) and in common practice following commercial approval.
Who may be able to join
- Signed and dated informed consent form
- Waldenström's macroglobulinemia diagnosis in need of treatment according to ESMO (European Society for Medical Oncology) guideline 2018
- Patients who received Zanubrutinib according to the Italian CUP or in common practice following Zanubrutinib commercial approval
- Treatment with zanubrutinib according to current SmPC (Summary of Product Characteristics)
- Treatment decision before inclusion into this non-interventional study
- Age ≥18 years
Who cannot join
- Contraindications according to SmPC for patients with WM
- Participation in an interventional clinical trial during zanubrutinib treatment
- Patients with disease progression during a BTKi treatment (if pre-treated with BTK, only those intolerants are considered eligible)
Trial locations and contacts
23 sites in 1 country.
23 sites in 1 country
Italy23 sites
A.O. SS. Antonio e Biagio e Cesare Arrigo - S.C.D.U. Ematologia
Alessandria
A.O.U. Ospedali Riuniti - Clinica di Ematologia
Ancona
Ospedale C. e G. Mazzoni - U.O.C. di Ematologia
Ascoli Piceno
AOU Policlinico Consorziale - U.O. Ematologia con Trapianto
Bari
Nuovo Ospedale degli Infermi - SSD Ematologia
Biella
Policlinico S. Orsola-Malpighi - Istituto di Ematologia "Seragnoli"
Bologna
Ospedale Centrale di Bolzano - Divisione di Ematologia e T.M.O.
Bolzano
Azienda Ospedaliero-Universitaria di Ferrara - Arcispedale Sant'Anna - Ematologia e fisiopatologia della coagulazione
Ferrara
Azienda Ospedaliera Universitaria Careggi - Unità funzionale di Ematologia
Florence
ASST Grande Ospedale Metropolitano Niguarda - S.C. Ematologia
Milan
Ospedale Maggiore Policlinico - Fondazione IRCCS Ca Granda - Ematologia
Milan
AOU Maggiore della Carità di Novara - SCDU Ematologia
Novara
AOU di Padova - Ematologia
Padova
A.O. Ospedali Riuniti Villa Sofia-Cervello - Divisione di Ematologia
Palermo
RCCS Policlinico S. Matteo di Pavia - Div. di Ematologia
Pavia
P.O. Spirito Santo di Pescara - UOC Ematologia Dipartimento Oncologico Ematologico - ASL Pescara
Pescara
Ospedale delle Croci - Ematologia
Ravenna
Azienda Unità Sanitaria Locale-IRCCS - Arcispedale Santa Maria Nuova - Ematologia
Reggio Emilia
Università Cattolica Sacro Cuore - Ematologia
Roma
AOU Senese - U.O.C. Ematologia
Siena
A.O.U. Città della Salute e della Scienza di Torino - Ematologia Universitaria
Torino
A.O.U. Città della Salute e della Scienza di Torino - S.C. Ematologia
Torino
Azienda Sanitaria Universitaria Friuli Centrale (ASU FC) - SOC Clinica Ematologica
Udine
About this study
Official title: Retrospective-prospective Study to Evaluate Treatment Management and Outcomes of Patients With Waldenström's Macroglobulinemia (WM) Treated in Italy According to the Zanubrutinib (Brukinsa®) Compassionate Use Program (CUP) and in Common Practice Following Commercial Approval
This is a non-interventional, observational, retrospective and prospective multicenter Italian study, to describe treatment management and outcomes of Waldenström's Macroglobulinemia (WM) patients treated according to the Italian Compassionate Use Program (CUP) and receiving zanubrutinib following its commercial approval.
- Conditions
- Waldenström's Macroglobulinemia (WM)
- Being tested
- Zanubrutinib
- Medical subject headings
- Waldenstrom Macroglobulinemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZanubrutinibDrug
Patients will be treated with Zanubrutinib as per routine clinical practice.
| Study group | Role | What they receive |
|---|---|---|
| Retrospective cohort | All patients with Waldenström's macroglobulinemia enrolled in Pre-Reimbursement Access Program (PRAP) of Zanubrutinib, as per Compassionate Use Program (CUP) of Zanubrutinib, and patients treated with commercial drug (Brukinsa®) from PRAP closure to the study start. | |
| Prospective cohort | Patients with Waldenström's macroglobulinemia treated with Zanubrutinibin clinical practice enrolled from the study start up to 12 months. Receives: Drug: Zanubrutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cumulative incidence of treatment discontinuation due to toxicity
Cumulative incidence of treatment discontinuation due to toxicity
Measured: From the date of first zanubrutinib administration to the date of definitive treatment discontinuation or dose reduction for any cause or death from any cause, from october 2020 up to 24 months since study start
Secondary outcomes (23)
Incidence of adverse events (AEs)
Incidence of adverse events (AEs)
Measured: Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Incidence of adverse events related to zanubrutinib.
Incidence of adverse events related to zanubrutinib.
Measured: Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Incidence of relevant adverse events.
Incidence of relevant adverse events.
Measured: Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Incidence of serious adverse events (SAEs).
Incidence of serious adverse events (SAEs).
Measured: Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Incidence of adverse events leading to death.
Incidence of adverse events leading to death.
Measured: Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Incidence of adverse events leading to treatment discontinuation.
Incidence of adverse events leading to treatment discontinuation.
Measured: Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Incidence of adverse events leading to dose reduction/interruption.
Incidence of adverse events leading to dose reduction/interruption.
Measured: Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Time to first onset of relevant adverse event.
Time to first onset of relevant adverse event.
Measured: Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
AEs ≥ G3 Hematological and non-hematological.
AEs ≥ G3 Hematological and non-hematological.
Measured: Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Impact of patients' characteristics and comorbidities on G3 or higher AEs and relevant adverse events development.
Impact of patients' characteristics and comorbidities on G3 or higher AEs and relevant adverse events development.
Measured: Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Frequency of transformation of WM to an aggressive lymphoma and frequency of secondary malignancies.
Frequency of transformation of WM to an aggressive lymphoma and frequency of secondary malignancies.
Measured: Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Major response rate (MRR)
Major response rate (MRR) (≥PR) (best reported response).
Measured: Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Overall response rate (ORR)
Overall response rate (ORR, defined as MRR plus minor response rate)
Measured: Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Best response
Best response (best reported response).
Measured: Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Progression-free survival (PFS)
Progression-free survival (PFS) including 6, 12, and 24-month PFS rate
Measured: Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Overall survival (OS)
Overall survival (OS) including 6, 12, and 24-month OS rate.
Measured: Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Time to treatment failure
Time to treatment failure (any treatment definitive discontinuation, incl. patient or investigator decision, toxicity, progression or death).
Measured: Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Duration of response (DOR)
Duration of response (DOR)
Measured: Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Change of IgM levels until end of zanubrutinib treatment.
Change of IgM levels until end of zanubrutinib treatment.
Measured: Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Impact of patients and disease characteristics, and biomarker test results (MYD88 and CXCR4, if available) on treatment response.
Impact of patients and disease characteristics, and biomarker test results (MYD88 and CXCR4, if available) on treatment response.
Measured: Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Hospital stays
Hospital stays comprises all planned and unplanned hospitalizations as well as emergency unit visits, regardless of whether there is an association with WM or not. All hospitalizations and emergency unit visits that started during therapy with zanubrutinib will be considered for hospital stays.
Measured: Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
EORTC-QLQ-C30
Quality of life (QoL) assessed with EORTC-QLQ-C30 questionnaire
Measured: Prospective cohort: up to 24 months (duration of study)
EQ-5D-5L
Quality of life (QoL) assessed with EQ-5D-5L questionnaire
Measured: Prospective cohort: up to 24 months (duration of study)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2024
- Study start13 Dec 2024
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Waldenström's Macroglobulinemia (WM)Studies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 212 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fondazione Italiana Linfomi - ETS
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Anna Maria Frustaci, Principal investigator, ASST Grande Ospedale Metropolitano Niguarda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06441214
- Sponsor's protocol ID
- FIL_BRUCE-ITA
- Status last verified
- Aug 2026
- First submitted
- 15 May 2024
- Last updated
- 24 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Retrospective-prospective Study to Evaluate Treatment Management and Outcomes of Patients With Waldenström's Macroglobulinemia (WM) Treated in Italy According to the Zanubrutinib (Brukinsa®) Compassionate Use Program (CUP) and in Common Practice Following Commercial Approval
- ClinicalTrials.gov ID
- NCT06441214
- Acronym / sponsor ID
- FIL_BRUCE-ITA
- Conditions
- Waldenström's Macroglobulinemia (WM)
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 212 participants (actual)
- Lead sponsor
- Fondazione Italiana Linfomi - ETSUniversity, hospital or other
- Study start
- 13 Dec 2024 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 4 Jun 2024 (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.
This is a non-interventional, observational, retrospective and prospective multicenter Italian study, to describe treatment management and outcomes of Waldenström's Macroglobulinemia (WM) patients treated according to the Italian Compassionate Use Program (CUP) and receiving zanubrutinib following its commercial approval.
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Retrospective cohort | – | –All patients with Waldenström's macroglobulinemia enrolled in Pre-Reimbursement Access Program (PRAP) of Zanubrutinib, as per Compassionate Use Program (CUP) of Zanubrutinib, and patients treated with commercial drug (Brukinsa®) from PRAP closure to the study start. |
| Prospective cohort | – | Drug: ZanubrutinibPatients with Waldenström's macroglobulinemia treated with Zanubrutinibin clinical practice enrolled from the study start up to 12 months. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with Waldenström's Macroglobulinemia (WM) treated in Italy according to the Zanubrutinib (Brukinsa®) compassionate use program (CUP) and in common practice following commercial approval.
Key inclusion criteria (6 listed)
- Signed and dated informed consent form
- Waldenström's macroglobulinemia diagnosis in need of treatment according to ESMO (European Society for Medical Oncology) guideline 2018
- Patients who received Zanubrutinib according to the Italian CUP or in common practice following Zanubrutinib commercial approval
- Treatment with zanubrutinib according to current SmPC (Summary of Product Characteristics)
- Treatment decision before inclusion into this non-interventional study
Key exclusion criteria (3 listed)
- Contraindications according to SmPC for patients with WM
- Participation in an interventional clinical trial during zanubrutinib treatment
- Patients with disease progression during a BTKi treatment (if pre-treated with BTK, only those intolerants are considered eligible)
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 |
|---|---|---|
| ZanubrutinibPatients will be treated with Zanubrutinib as per routine clinical practice. | Drug | Prospective cohort |
Primary outcome
Cumulative incidence of treatment discontinuation due to toxicity
Time frame: From the date of first zanubrutinib administration to the date of definitive treatment discontinuation or dose reduction for any cause or death from any cause, from october 2020 up to 24 months since study start
Cumulative incidence of treatment discontinuation due to toxicity
23 secondary outcomes
Incidence of adverse events (AEs)
Time frame: Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Incidence of adverse events related to zanubrutinib.
Time frame: Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Incidence of relevant adverse events.
Time frame: Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Incidence of serious adverse events (SAEs).
Time frame: Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Incidence of adverse events leading to death.
Time frame: Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Incidence of adverse events leading to treatment discontinuation.
Time frame: Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Incidence of adverse events leading to dose reduction/interruption.
Time frame: Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Time to first onset of relevant adverse event.
Time frame: Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
AEs ≥ G3 Hematological and non-hematological.
Time frame: Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Impact of patients' characteristics and comorbidities on G3 or higher AEs and relevant adverse events development.
Time frame: Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Frequency of transformation of WM to an aggressive lymphoma and frequency of secondary malignancies.
Time frame: Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Major response rate (MRR)
Time frame: Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Overall response rate (ORR)
Time frame: Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Best response
Time frame: Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Progression-free survival (PFS)
Time frame: Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Overall survival (OS)
Time frame: Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Time to treatment failure
Time frame: Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Duration of response (DOR)
Time frame: Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Change of IgM levels until end of zanubrutinib treatment.
Time frame: Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Impact of patients and disease characteristics, and biomarker test results (MYD88 and CXCR4, if available) on treatment response.
Time frame: Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Hospital stays
Time frame: Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
EORTC-QLQ-C30
Time frame: Prospective cohort: up to 24 months (duration of study)
EQ-5D-5L
Time frame: Prospective cohort: up to 24 months (duration of study)
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 24 Aug 2026.
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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.
Anna Maria Frustaci principal investigator
ASST Grande Ospedale Metropolitano Niguarda
23 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Waldenström's Macroglobulinemia (WM), run by Fondazione Italiana Linfomi - ETS at 23 sites in Italy.
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 6 inclusion and 3 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 24 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in Italy. 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.
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?
Cumulative incidence of treatment discontinuation due to toxicity (time frame: From the date of first zanubrutinib administration to the date of definitive treatment discontinuation or dose reduction for any cause or death from any cause, from october 2020 up to 24 months since study start). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 24 Aug 2026.