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.

Waldenström's Macroglobulinemia (WM) Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06441214
• Other study ID #: FIL_BRUCE-ITA
• Status: Not yet recruiting
• Start date: July 2024
• Est. completion date: July 2026

Study information

• Verified date: May 2024
• Source: Fondazione Italiana Linfomi - ETS
• Contact: Samantha Dattoli
• Phone: +390599769916
• Email: sdattoli[@]filinf.it
• Is FDA regulated: No
• Study type: Observational

Clinical 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 approval.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 125
• Est. completion date: July 2026
• Est. primary completion date: July 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Waldenstrom Macroglobulinemia
• Waldenström's Macroglobulinemia (WM)

Intervention

Drug:
• Zanubrutinib
Patients will be treated with Zanubrutinib as per routine clinical practice.

Locations

Country	Name	City	State
Italy	A.O. SS. Antonio e Biagio e Cesare Arrigo - S.C.D.U. Ematologia	Alessandria
Italy	A.O.U. Ospedali Riuniti - Clinica di Ematologia	Ancona
Italy	Ospedale C. e G. Mazzoni - U.O.C. di Ematologia	Ascoli Piceno
Italy	AOU Policlinico Consorziale - U.O. Ematologia con Trapianto	Bari
Italy	Nuovo Ospedale degli Infermi - SSD Ematologia	Biella
Italy	Policlinico S. Orsola-Malpighi - Istituto di Ematologia "Seragnoli"	Bologna
Italy	Ospedale Centrale di Bolzano - Divisione di Ematologia e T.M.O.	Bolzano
Italy	Azienda Ospedaliera Universitaria Policlinico - S. Marco - UOC di Ematologia	Catania
Italy	Azienda Ospedaliero-Universitaria di Ferrara - Arcispedale Sant'Anna - Ematologia e fisiopatologia della coagulazione	Ferrara
Italy	Azienda Ospedaliera Universitaria Careggi - Unità funzionale di Ematologia	Firenze
Italy	Ospedale Policlinico San Martino S.S.R.L. - IRCCS per l'Oncologia - Ematologia e terapie cellulari	Genova
Italy	ASST Grande Ospedale Metropolitano Niguarda - S.C. Ematologia	Milano
Italy	IEO Istituto Europeo di Oncologia - Divisione Ematoncologia	Milano
Italy	Ospedale Maggiore Policlinico - Fondazione IRCCS Ca Granda - Ematologia	Milano
Italy	AOU Maggiore della Carità di Novara - SCDU Ematologia	Novara
Italy	AOU di Padova - Ematologia	Padova
Italy	A.O. Ospedali Riuniti Villa Sofia-Cervello - Divisione di Ematologia	Palermo
Italy	RCCS Policlinico S. Matteo di Pavia - Div. di Ematologia	Pavia
Italy	P.O. Spirito Santo di Pescara - UOC Ematologia Dipartimento Oncologico Ematologico - ASL Pescara	Pescara
Italy	AOU Pisana - U.O. Ematologia	Pisa
Italy	Ospedale delle Croci - Ematologia	Ravenna
Italy	Azienda Unità Sanitaria Locale-IRCCS - Arcispedale Santa Maria Nuova - Ematologia	Reggio Emilia
Italy	Università Cattolica Sacro Cuore - Ematologia	Roma
Italy	AOU Senese - U.O.C. Ematologia	Siena
Italy	Ospedale "G. Mazzini" - UOS Ematologia	Teramo
Italy	A.O.U. Città 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	Torino
Italy	Azienda Sanitaria Universitaria Friuli Centrale (ASU FC) - SOC Clinica Ematologica	Udine

Sponsors (1)

Lead Sponsor	Collaborator
Fondazione Italiana Linfomi - ETS

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cumulative incidence of treatment discontinuation due to toxicity	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	Incidence of adverse events (AEs)	Incidence of adverse events (AEs)	Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Secondary	Incidence of adverse events related to zanubrutinib.	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)
Secondary	Incidence of relevant adverse events.	Incidence of relevant adverse events.	Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Secondary	Incidence of serious adverse events (SAEs).	Incidence of serious adverse events (SAEs).	Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Secondary	Incidence of adverse events leading to death.	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)
Secondary	Incidence of adverse events leading to treatment discontinuation.	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)
Secondary	Incidence of adverse events leading to dose reduction/interruption.	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)
Secondary	Time to first onset of relevant adverse event.	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)
Secondary	AEs = G3 Hematological and non-hematological.	AEs = G3 Hematological and non-hematological.	Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Secondary	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.	Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Secondary	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.	Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Secondary	Major response rate (MRR)	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)
Secondary	Overall response rate (ORR)	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)
Secondary	Best response	Best response (best reported response).	Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Secondary	Progression-free survival (PFS)	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)
Secondary	Overall survival (OS)	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)
Secondary	Time to treatment failure	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)
Secondary	Duration of response (DOR)	Duration of response (DOR)	Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Secondary	Change of IgM levels until end of zanubrutinib treatment.	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)
Secondary	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.	Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Secondary	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.	Retrospective cohort: from october 2020 until the study start. Prospective cohort: up to 24 months (duration of study)
Secondary	EORTC-QLQ-C30	Quality of life (QoL) assessed with EORTC-QLQ-C30 questionnaire	Prospective cohort: up to 24 months (duration of study)
Secondary	EQ-5D-5L	Quality of life (QoL) assessed with EQ-5D-5L questionnaire	Prospective cohort: up to 24 months (duration of study)