Clinical trial NCT05326308: Zanubrutinib in Patients With Waldenström's Macroglobulinemia, Chronic Lymphocytic Leukemia, Marginal Zone Lymphoma and Follicular Lymphoma
Official title: Zanubrutinib (Brukinsa®) in Patients With Waldenström's Macroglobulinemia (WM), Chronic Lymphocytic Leukemia (CLL), Marginal Zone Lymphoma (MZL) and Follicular Lymphoma (FL) - a Prospective Multicenter Observational Cohort Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Waldenström's Macroglobulinemia
Chronic Lymphocytic Leukemia
Marginal Zone Lymphoma
Follicular Lymphoma
Keywords: Waldenström's Macroglobulinemia
Zanubrutinib
Brukinsa
Chronic Lymphocytic Leukemia
Marginal Zone Lymphoma
Follicular Lymphoma
Lead sponsor: iOMEDICO AG
Sponsor class: INDUSTRY
Collaborators: name: BeiGene Switzerland GmbH
First posted: 2022-04-13
Enrollment: 605
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult patients with Waldenström's macroglobulinemia (WM), Chronic Lymphocytic Leukemia (CLL), Marginal Zone Lymphoma (MZL) or Follicular Lymphoma (FL) in need of treatment with decision for treatment with zanubrutinib (Brukinsa®) according to the Summary of Product Characteristics (SmPC).

Brief summary: The objective of this NIS is to evaluate medical resource utilization, where data is rare in all cohorts, patient's QoL and effectiveness of zanubrutinib treatment in adult patients with WM, CLL, MZL and FL in a real-world setting.

Detailed description: ARIADNE will collect and analyze data of adult patients with WM, CLL, MZL or FL in need of treatment. The study will explore the medical resource utilization during therapy with zanubrutinib (Brukinsa®). Further aims are to assess effectiveness, safety and tolerability of the treatment as well as treatment satisfaction and biomarkers. These data will be supplemented by the assessment of patient-reported outcomes (PROs)/ health-related quality of life (QoL).

Since treatment options for MW, CLL, MZL or FL are limited and the most important factor is to keep or improve QoL of the patients, there is an urge for real-world clinical data of patients treated with zanubrutinib, especially focusing on patients already treated upfront with a BTK inhibitor, older patients and patients with comorbidities.

Eligibility criteria: Inclusion Criteria:

* Waldenström's macroglobulinemia (all treatment lines) OR
* Chronic lymphocytic leukemia (all treatment lines) OR
* Marginal zone lymphoma (≥2 treatment line and at least one anti-CD20 antibody-based previous therapy)
* Follicular lymphoma (≥3 treatment line)
* Signed and dated informed consent form
* Treatment with zanubrutinib according to current SmPC for WM, CLL and MZL
* Treatment with zanubrutinib + obinutuzumab for FL according to current SmPC
* Treatment decision before inclusion into this non-interventional study
* Age ≥18 years.

Exclusion Criteria:

* Contraindications according to SmPC for patients with WM, CLL, MZL or FL
* Participation in an interventional clinical trial during zanubrutinib treatment.

Primary outcomes:
measure: Medical resource utilization
timeFrame: During zanubrutinib treatment, up to 6.3 years
Secondary outcomes:
measure: Global health-related quality of life (QoL) collected via EORTC QLQ-C30 during course of treatment and follow-up
timeFrame: During zanubrutinib treatment and follow-up, up to 6.3 years
measure: Global health-related quality of life (QoL) collected via EQ-5D-5L during course of treatment and follow-up
timeFrame: During zanubrutinib treatment and follow-up, up to 6.3 years
measure: Incidence of (serious) adverse events ((S)AEs)
timeFrame: Start of zanubrutinib treatment until 30 days after end of zanubrutinib treatment
measure: Incidence of (serious) adverse drug reactions ((S)ADRs)
timeFrame: Start of zanubrutinib treatment until end of study, up to 6.3 years
measure: Incidence of adverse events of special interest (AESIs)
timeFrame: Start of zanubrutinib treatment until 30 days after end of zanubrutinib treatment
measure: Time to AESIs
timeFrame: Start of zanubrutinib treatment until 30 days after end of zanubrutinib treatment
measure: Time to neutropenia
timeFrame: Start of zanubrutinib treatment until 30 days after end of zanubrutinib treatment
measure: Rate of neutropenia grade ≥3
timeFrame: Start of zanubrutinib treatment until 30 days after end of zanubrutinib treatment
measure: Proportion of patients with complete response (CR) or very good partial response (VGPR) (best reported response)
timeFrame: During zanubrutinib treatment, up to 6.3 years
measure: In the WM cohort only: Major response rate (MRR)
timeFrame: During zanubrutinib treatment, up to 6.3 years
measure: In the WM cohort only: Best response
timeFrame: During zanubrutinib treatment, up to 6.3 years
measure: In the WM cohort only: IgM levels
timeFrame: During zanubrutinib treatment, up to 6.3 years
measure: Progression-free Survival (PFS)
timeFrame: Treatment start with zanubrutinib until end of study, up to 6.3 years
measure: 6-, 12-, 18- and 24-month PFS rate
timeFrame: 6, 12, and 24 months after start of zanubrutinib treatment
measure: Overall Survival (OS)
timeFrame: Treatment start with zanubrutinib until end of study, up to 6.3 years
measure: 6-, 12-, 18- and 24-month OS rate
timeFrame: 6, 12, and 24 months after start of zanubrutinib treatment
measure: WM Cohort: Overall response rate (ORR)
timeFrame: During zanubrutinib treatment, up to 6.3 years
measure: WM Cohort: Best overall response rate (ORR)
timeFrame: During zanubrutinib treatment, up to 6.3 years
measure: CLL Cohort: Overall response rate (ORR)
timeFrame: During zanubrutinib treatment, up to 6.3 years
measure: CLL Cohort: Best overall response rate (ORR)
timeFrame: During zanubrutinib treatment, up to 6.3 years
measure: MZL Cohort: Overall response rate (ORR)
timeFrame: During zanubrutinib treatment, up to 6.3 years
measure: MZL Cohort: Best overall response rate (ORR)
timeFrame: During zanubrutinib treatment, up to 6.3 years
measure: FL Cohort: Overall response rate (ORR)
timeFrame: During zanubrutinib treatment, up to 6.3 years
measure: FL Cohort: Best overall response rate (ORR)
timeFrame: During zanubrutinib treatment, up to 6.3 years
measure: Time to treatment failure (TTF)
timeFrame: Treatment start with zanubrutinib until end of treatment, up to 6.3 years
measure: Frequency of blood product transfusion
timeFrame: During zanubrutinib treatment, up to 6.3 years
measure: WM Cohort: Change of IgM levels until end of zanubrutinib treatment
timeFrame: Baseline and end of zanubrutinib treatment, up to 6.3 years
measure: Therapy decision making
timeFrame: Baseline
measure: Time from first diagnosis of WM, CLL, MZL or FL to zanubrutinib treatment start
timeFrame: Baseline
measure: Previous therapies
timeFrame: Baseline
measure: Daily dose of zanubrutinib
timeFrame: During zanubrutinib treatment, up to 6.3 years
measure: FL cohort: Daily dose of obinutuzumab
timeFrame: During zanubrutinib treatment, up to 6.3 years
measure: Dose modifications of zanubrutinib
timeFrame: During zanubrutinib treatment, up to 6.3 years
measure: FL cohort: Dose modifications of obinutuzumab
timeFrame: During zanubrutinib treatment, up to 6.3 years
measure: Therapy interruptions of zanubrutinib
timeFrame: During zanubrutinib treatment, up to 6.3 years
measure: FL cohort: Therapy interruptions of obinutuzumab
timeFrame: During zanubrutinib treatment, up to 6.3 years
measure: Dose intensity of zanubrutinib
timeFrame: During zanubrutinib treatment, up to 6.3 years
measure: FL cohort: Dose intensity of obinutuzumab
timeFrame: During zanubrutinib treatment, up to 6.3 years
measure: Treatment duration with zanubrutinib
timeFrame: During zanubrutinib treatment, up to 6.3 years
measure: FL cohort: Treatment duration with obinutuzumab
timeFrame: During zanubrutinib treatment, up to 6.3 years
measure: Subsequent antineoplastic therapies
timeFrame: End of zanubrutinib treatment until end of study, up to 6.3 years
measure: Frequency for concomitant medication during zanubrutinib treatment
timeFrame: During zanubrutinib treatment, up to 6.3 years
measure: Frequency of antibiotic use for prophylactic reasons during zanubrutinib treatment
timeFrame: During zanubrutinib treatment, up to 6.3 years
measure: Frequency of antibiotic use for treatment of AEs during zanubrutinib treatment
timeFrame: During zanubrutinib treatment, up to 6.3 years
measure: Frequency of antibiotic use in patients with neutropenia during zanubrutinib treatment
timeFrame: During zanubrutinib treatment, up to 6.3 years
Other outcomes:
measure: Patients' treatment expectation and satisfaction
timeFrame: Baseline, 3 months after treatment start with zanubrutinib, end of treatment
measure: Physicians' treatment expectation and satisfaction
timeFrame: Baseline, 3 months after treatment start with zanubrutinib, end of treatment
measure: Collection of biomarker test results (according to clinical routine)
timeFrame: Baseline, up to 6.3 years
measure: Patient management during SARS-Covid-19 pandemic
timeFrame: Baseline and end of zanubrutnib treatment, up to 6.3 years
Locations:
city: Salzburg
country: Austria
facility: Universitätsklinikum Salzburg, Klinik für Innere Medizin III
city: Lübeck
country: Germany
facility: Lübecker Onkologische Schwerpunktpraxis
state: Schleswig-Holstein
Study officials:
affiliation: Lübecker Onkologische Schwerpunktpraxis
name: Jens Kisro, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Universitätsklinikum Salzburg, Klinik für Innere Medizin III
name: Richard Greil, Prof.
role: PRINCIPAL_INVESTIGATOR
References: