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.

August 21, 2026 updated by: Fondazione Italiana Linfomi - ETS

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

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

Intervention / Treatment

Intervention / Treatment

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

Study Type

Study Type

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

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
212

Contacts and Locations

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

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Italy
      • Alessandria, Italy
        • A.O. SS. Antonio e Biagio e Cesare Arrigo - S.C.D.U. Ematologia
      • Ancona, Italy
        • A.O.U. Ospedali Riuniti - Clinica di Ematologia
      • Ascoli Piceno, Italy
        • Ospedale C. e G. Mazzoni - U.O.C. di Ematologia
      • Bari, Italy
        • AOU Policlinico Consorziale - U.O. Ematologia con Trapianto
      • Biella, Italy
        • Nuovo Ospedale degli Infermi - SSD Ematologia
      • Bologna, Italy
        • Policlinico S. Orsola-Malpighi - Istituto di Ematologia "Seragnoli"
      • Bolzano, Italy
        • Ospedale Centrale di Bolzano - Divisione di Ematologia e T.M.O.
      • Ferrara, Italy
        • Azienda Ospedaliero-Universitaria di Ferrara - Arcispedale Sant'Anna - Ematologia e fisiopatologia della coagulazione
      • Florence, Italy
        • Azienda Ospedaliera Universitaria Careggi - Unità funzionale di Ematologia
      • Milan, Italy
        • Ospedale Maggiore Policlinico - Fondazione IRCCS Ca Granda - Ematologia
      • Milan, Italy
        • ASST Grande Ospedale Metropolitano Niguarda - S.C. Ematologia
      • Novara, Italy
        • AOU Maggiore della Carità di Novara - SCDU Ematologia
      • Padova, Italy
        • AOU di Padova - Ematologia
      • Palermo, Italy
        • A.O. Ospedali Riuniti Villa Sofia-Cervello - Divisione di Ematologia
      • Pavia, Italy
        • RCCS Policlinico S. Matteo di Pavia - Div. di Ematologia
      • Pescara, Italy
        • P.O. Spirito Santo di Pescara - UOC Ematologia Dipartimento Oncologico Ematologico - ASL Pescara
      • Ravenna, Italy
        • Ospedale delle Croci - Ematologia
      • Reggio Emilia, Italy
        • Azienda Unità Sanitaria Locale-IRCCS - Arcispedale Santa Maria Nuova - Ematologia
      • Roma, Italy
        • Università Cattolica Sacro Cuore - Ematologia
      • Siena, Italy
        • AOU Senese - U.O.C. Ematologia
      • Torino, Italy
        • A.O.U. Citta della Salute e della Scienza di Torino - Ematologia Universitaria
      • Torino, Italy
        • A.O.U. Città della Salute e della Scienza di Torino - S.C. Ematologia
      • Udine, Italy
        • Azienda Sanitaria Universitaria Friuli Centrale (ASU FC) - SOC Clinica Ematologica

Participation Criteria

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

Eligibility Criteria

Eligibility Criteria

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

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

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.

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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)

Study Plan

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

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.
Drug: Zanubrutinib
Patients will be treated with Zanubrutinib as per routine clinical practice.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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 (AEs)
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 adverse events related to zanubrutinib.
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 relevant adverse events.
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 serious adverse events (SAEs).
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 death.
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 treatment discontinuation.
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)
Incidence of adverse events leading to dose reduction/interruption.
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)
Time to first onset of relevant adverse event.
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)
AEs ≥ G3 Hematological and non-hematological.
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)
Impact of patients' characteristics and comorbidities on G3 or higher AEs and relevant adverse events development.
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)
Frequency of transformation of WM to an aggressive lymphoma and frequency of secondary malignancies.
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)
Major response rate (MRR) (≥PR) (best reported response).
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)
Overall response rate (ORR, defined as MRR plus minor response rate)
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)
Best response (best reported response).
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)
Progression-free survival (PFS) including 6, 12, and 24-month PFS rate
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)
Overall survival (OS) including 6, 12, and 24-month OS rate.
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)
Time to treatment failure (any treatment definitive discontinuation, incl. patient or investigator decision, toxicity, progression or death).
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)
Duration of response (DOR)
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)
Change of IgM levels until end of zanubrutinib treatment.
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)
Impact of patients and disease characteristics, and biomarker test results (MYD88 and CXCR4, if available) on treatment response.
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)
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.
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)
Quality of life (QoL) assessed with EORTC-QLQ-C30 questionnaire
Prospective cohort: up to 24 months (duration of study)
EQ-5D-5L
Time Frame: Prospective cohort: up to 24 months (duration of study)
Quality of life (QoL) assessed with EQ-5D-5L questionnaire
Prospective cohort: up to 24 months (duration of study)

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Fondazione Italiana Linfomi - ETS

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Anna Maria Frustaci, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 13, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 15, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 28, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 4, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 24, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 21, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • FIL_BRUCE-ITA

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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

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