Zanubrutinib in Patients With Waldenström's Macroglobulinemia (ARIADNE)
Study Details
Study Description
Brief Summary
The objective of this non-interventional study (NIS) is to evaluate medical resource utilization, patient's quality of life (QoL), safety and effectiveness of zanubrutinib treatment in adult patients with Waldenström's macroglobulinemia in a real-world setting.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
Detailed Description
ARIADNE will collect and analyze data from adult Waldenström's macroglobulinemia patients 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 Waldenström's macroglobulinemia are limited and the most important factor is to keep or improve quality of life (QoL) of the patients, there is an urge for real-world clinical data of Waldenström's macroglobulinemia patients treated with zanubrutinib, especially focusing on patients already treated upfront with a BTK inhibitor, older patients and patients with comorbidities.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Study Cohort 150 patients (excluding screening failures, patients with off-label use or with violation of inclusion/exclusion criteria identified after treatment start) receiving zanubrutinib (Brukinsa®) |
Drug: Zanubrutinib
according to the Summary of Product Characteristics (SmPC).
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Medical resource utilization [During zanubrutinib treatment, up to 5 years]
Frequency of hospitalizations, i.e. number of hospital stays plus number of emergency unit visits (without hospitalization) per patient
Secondary Outcome Measures
- Global health-related quality of life (QoL) collected via EORTC QLQ-C30 during course of treatment and follow-up [During zanubrutinib treatment and follow-up, up to 5 years]
Course of QoL during treatment and follow-up (collected via European Organisation for research and treatment of cancer quality of life in cancer patient questionnaire (EORTC QLQ-C30). Scoring of the questionnaire will be performed according to the respective manual.
- Global health-related quality of life (QoL) collected via EQ-5D-5L during course of treatment and follow-up [During zanubrutinib treatment and follow-up, up to 5 years]
Course of QoL during treatment and follow-up (collected via European quality of life 5 dimension 5 level version (EQ-5D-5L)). Scoring of the questionnaire will be performed according to the respective manual.
- Incidence of (serious) adverse events ((S)AEs) [Start of zanubrutinib treatment until 30 days after end of zanubrutinib treatment]
Incidence of (S)AEs; (S)AEs will be summarized by the most recent Medical Dictionary for Regulatory Activities (MedDRA) system organ class and preferred term.
- Incidence of (serious) adverse drug reactions ((S)ADRs) [Start of zanubrutinib treatment until end of study, up to 5 years]
Incidence of (S)ADRs related to zanubrutinib
- Incidence of adverse events of special interest (AESIs) [Start of zanubrutinib treatment until 30 days after end of zanubrutinib treatment]
Incidence of AESIs
- Time to AESIs [Start of zanubrutinib treatment until 30 days after end of zanubrutinib treatment]
The time to first onset of AESIs.
- Time to neutropenia [Start of zanubrutinib treatment until 30 days after end of zanubrutinib treatment]
The time to first onset of neutropenia grade ≥3 (MedDRA terms: neutropenia and neutrophil count decrease).
- Rate of neutropenia grade ≥3 [Start of zanubrutinib treatment until 30 days after end of zanubrutinib treatment]
Rate of patients with neutropenia grade ≥3 during zanubrutinib treatment. Neutropenia incorporates the MedDRA terms: neutropenia and neutrophil count decrease.
- Proportion of patients with complete response (CR) or very good partial response (VGPR) (best reported response) [During zanubrutinib treatment, up to 5 years]
The proportion of patients with a best overall response of CR or VGPR.
- Major response rate (MRR) [During zanubrutinib treatment, up to 5 years]
MRR is defined as the proportion of patients with a best overall response of complete response (CR), very good partial response (VGPR) or partial response (PR).
- Best response [During zanubrutinib treatment, up 5 years]
Best response is defined as best reported response during study treatment (CR, VGPR, PR, MR, SD or PD).
- Progression-free Survival (PFS) [Treatment start with zanubrutinib until end of study, up to 5 years]
PFS is defined as the time from treatment start until progression or death from any cause, whichever comes first.
- 6-, 12-, and 24-month PFS rate [6, 12, and 24 months after start of zanubrutinib treatment]
Percentage of patients without disease progression or death from any cause at 6, 12, and 24 months after start of zanubrutinib treatment.
- Overall Survival (OS) [Treatment start with zanubrutinib until end of study, up to 5 years]
OS is defined as the time from treatment start until death.
- 6-, 12-, and 24-month OS rate [6, 12, and 24 months after start of zanubrutinib treatment]
Percentage of patients alive at 6, 12, and 24 months after start of zanubrutinib treatment.
- Time to treatment failure (TTF) [Treatment start with zanubrutinib until end of treatment, up to 5 years]
TTF is defined as time interval from treatment start to discontinuation of treatment because of disease progression, treatment toxicity, switch of therapy of any reason, and death.
- Frequency of blood product transfusion [During zanubrutinib treatment, up to 5 years]
The number of patients receiving blood product transfusion, the number of transfusions per patient and the kind of transfusion (e.g., erythrocytes, thrombocytes).
- Change of IgM levels until end of zanubrutinib treatment [Baseline and end of zanubrutinib treatment, up to 5 years]
Difference between the baseline value and the end of treatment value of the IgM level.
- Therapy decision making [Baseline]
Frequency and weighting of distinct parameters affecting therapy choice of the treating physician assessed by project specific questionnaire
- Time from first diagnosis of WM to zanubrutinib treatment start [Baseline]
Time from first diagnosis of WM to zanubrutinib treatment start including timing and duration of possible watch & wait strategy.
- Previous therapies [Baseline]
Key details of previous therapies (including plasmapheresis and transplantations)
- Details of zanubrutinib treatment [During zanubrutinib treatment, up to 5 years]
To describe treatment details of zanubrutinib, frequency tables will be provided including the daily dose, therapy modifications (reduction and increase) with reasons, treatment interruptions with reasons and reasons for treatment termination. Dose intensity (absolute and relative) as well as the treatment duration will be given using descriptive statistics.
- Subsequent antineoplastic therapies [End of zanubrutinib treatment until end of study, up to 5 years]
Key details of subsequent antineoplastic therapies after zanubrutinib (including plasmapheresis and transplantations): duration (descriptive statistics), number, substances and reason for end of subsequent treatments (frequencies).
- Frequency for concomitant medication [During zanubrutinib treatment, up to 5 years]
Substances (WHO-ATC level 2), ongoing status and indication (frequencies)
- Frequency of antibiotic use for prophylactic reasons during zanubrutinib treatment [During zanubrutinib treatment, up to 5 years]
Proportion of patients with at least one-time antibiotic use for prophylactic reasons during zanubrutinib treatment.
- Frequency of antibiotic use for treatment of AEs during zanubrutinib treatment [During zanubrutinib treatment, up to 5 years]
Proportion of patients taking at least one-time antibiotics for treatment of AEs during zanubrutinib treatment.
- Frequency of antibiotic use in patients with neutropenia during zanubrutinib treatment [During zanubrutinib treatment, up to 5 years]
Proportion of patients presenting with neutropenia during zanubrutinib treatment taking at least one-time antibiotics.
Other Outcome Measures
- Patients' treatment expectation and satisfaction [Baseline, 3 months after treatment start with zanubrutinib, end of treatment]
Patients' treatment expectation and satisfaction (assessed via project specific questionnaire) will be analyzed by time point, using absolute and relative frequencies.
- Physicians' treatment expectation and satisfaction [Baseline, 3 months after treatment start with zanubrutinib, end of treatment]
Physicians' treatment expectation and satisfaction (assessed via project specific questionnaire) will be analyzed by time point, using absolute and relative frequencies.
- Collection of biomarker test results (according to clinical routine) [Baseline, up to 5 years]
Number of patients with biomarker testing as well as sample types, test methods and test results of biomarker testing per biomarker will be provided. Information on the testing of MYD88 and CXCR4 is mandatory.
- Patient management during SARS-Covid-19 pandemic [Baseline and end of zanubrutnib treatment, up to 5 years]
The patient management during SARS-Covid-19 pandemic (assessed via project specific questionnaire) (patient supervised by oncologist or additionally by family doctor) will be presented by frequency tables.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Signed and dated informed consent form
-
Waldenström's macroglobulinemia
-
Treatment with zanubrutinib 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 Waldenström's macroglobulinemia
-
Participation in an interventional clinical trial during zanubrutinib treatment
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Universitätsklinikum Salzburg, Klinik für Innere Medizin III | Salzburg | Austria | A-5020 | |
| 2 | Lübecker Onkologische Schwerpunktpraxis | Lübeck | Schleswig-Holstein | Germany | D-23562 |
Sponsors and Collaborators
- iOMEDICO AG
- BeiGene Switzerland GmbH
Investigators
- Principal Investigator: Jens Kisro, Dr., Lübecker Onkologische Schwerpunktpraxis
- Principal Investigator: Richard Greil, Prof., Universitätsklinikum Salzburg, Klinik für Innere Medizin III
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- IOM-100461