Zanubrutinib in Patients With Waldenström's Macroglobulinemia, Chronic Lymphocytic Leukemia, Marginal Zone Lymphoma and Follicular Lymphoma (ARIADNE)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Follicular Lymphoma; Marginal Zone Lymphoma; Chronic Lymphocytic Leukemia; Waldenström's Macroglobulinemia
• Intervention / Treatment: Drug: Zanubrutinib; Drug: Obinutuzumab

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.

• Study Type: Observational
• Enrollment (Estimated): 400

Contacts and Locations

• Study Contact: Name: Daniel Kummer, Dr.; Phone Number: +49761152420; Email: ariadne@iomedico.com

Study Locations

• Austria
  • Salzburg, Austria, A-5020
    • Recruiting
    • Universitätsklinikum Salzburg, Klinik für Innere Medizin III
    • Contact: Richard Greil, Prof.; Phone Number: +435725525800; Email: r.greil@salk.at
• Germany
  • Schleswig-Holstein
    • Lübeck, Schleswig-Holstein, Germany, D-23562
      • Recruiting
      • Lübecker Onkologische Schwerpunktpraxis
      • Contact: Jens Kisro, Dr.; Phone Number: +4945170797226; Email: jens-kisro@t-online.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• 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).

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Waldenström's Macroglobulinemia; 75 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: Brukinsa®
Chronic Lymphocytic Leukemia; 250 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: Brukinsa®
Marginal Zone Lymphoma; 37 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: Brukinsa®
Follicular Lymphoma; 38 patients (excluding screening failures, patients with off-label use or with violation of inclusion/exclusion criteria identified after treatment start) receiving zanubrutinib (Brukinsa®) in combination with obinutuzumab (Gazyvaro®)	Drug: Zanubrutinib; according to the Summary of Product Characteristics (SmPC).; Other Names: Brukinsa®; Drug: Obinutuzumab; according to the Summary of Product Characteristics (SmPC).; Other Names: Gazyvaro®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Medical resource utilization	Frequency of hospitalizations, i.e. number of hospital stays plus number of emergency unit visits (without hospitalization) per patient	During zanubrutinib treatment, up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Global health-related quality of life (QoL) collected via EORTC QLQ-C30 during course of treatment and follow-up	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.	During zanubrutinib treatment and follow-up, up to 5 years
Global health-related quality of life (QoL) collected via EQ-5D-5L during course of treatment and follow-up	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.	During zanubrutinib treatment and follow-up, up to 5 years
Incidence of (serious) adverse events ((S)AEs)	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.	Start of zanubrutinib treatment until 30 days after end of zanubrutinib treatment
Incidence of (serious) adverse drug reactions ((S)ADRs)	Incidence of (S)ADRs related to zanubrutinib	Start of zanubrutinib treatment until end of study, up to 5 years
Incidence of adverse events of special interest (AESIs)	Incidence of AESIs	Start of zanubrutinib treatment until 30 days after end of zanubrutinib treatment
Time to AESIs	The time to first onset of AESIs.	Start of zanubrutinib treatment until 30 days after end of zanubrutinib treatment
Time to neutropenia	The time to first onset of neutropenia grade ≥3 (MedDRA terms: neutropenia and neutrophil count decrease).	Start of zanubrutinib treatment until 30 days after end of zanubrutinib treatment
Rate of neutropenia grade ≥3	Rate of patients with neutropenia grade ≥3 during zanubrutinib treatment. Neutropenia incorporates the MedDRA terms: neutropenia and neutrophil count decrease.	Start of zanubrutinib treatment until 30 days after end of zanubrutinib treatment
Proportion of patients with complete response (CR) or very good partial response (VGPR) (best reported response)	The proportion of patients with a best overall response of CR or VGPR.	During zanubrutinib treatment, up to 5 years
Progression-free Survival (PFS)	PFS is defined as the time from treatment start until progression or death from any cause, whichever comes first.	Treatment start with zanubrutinib until end of study, up to 5 years
Overall Survival (OS)	OS is defined as the time from treatment start until death.	Treatment start with zanubrutinib until end of study, up to 5 years
Time to treatment failure (TTF)	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.	Treatment start with zanubrutinib until end of treatment, up to 5 years
Frequency of blood product transfusion	The number of patients receiving blood product transfusion, the number of transfusions per patient and the kind of transfusion (e.g., erythrocytes, thrombocytes).	During zanubrutinib treatment, up to 5 years
Therapy decision making	Frequency and weighting of distinct parameters affecting therapy choice of the treating physician assessed by project specific questionnaire	Baseline
Frequency of antibiotic use for prophylactic reasons during zanubrutinib treatment	Proportion of patients with at least one-time antibiotic use for prophylactic reasons during zanubrutinib treatment.	During zanubrutinib treatment, up to 5 years
Frequency of antibiotic use for treatment of AEs during zanubrutinib treatment	Proportion of patients taking at least one-time antibiotics for treatment of AEs during zanubrutinib treatment.	During zanubrutinib treatment, up to 5 years
Frequency of antibiotic use in patients with neutropenia during zanubrutinib treatment	Proportion of patients presenting with neutropenia during zanubrutinib treatment taking at least one-time antibiotics.	During zanubrutinib treatment, up to 5 years
In the WM cohort only: Major response rate (MRR)	MRR is defined as the proportion of patients with a best overall response ≥ PR (partial response)	During zanubrutinib treatment, up to 5 years
In the WM cohort only: Best response	Best response is defined as best reported response during study treatment CR (complete response) or VGPR (very good partial response).	During zanubrutinib treatment, up to 5 years
In the WM cohort only: IgM levels	Change of IgM levels until end of zanubrutinib treatment for WM cohort.	During zanubrutinib treatment, up to 5 years
6-, 12-, 18- and 24-month PFS rate	Percentage of patients without disease progression or death from any cause at 6, 12, and 24 months after start of zanubrutinib treatment.	6, 12, and 24 months after start of zanubrutinib treatment
6-, 12-, 18- and 24-month OS rate	Percentage of patients alive at 6, 12, and 24 months after start of zanubrutinib treatment.	6, 12, and 24 months after start of zanubrutinib treatment
WM Cohort: Overall response rate (ORR)	For the WM cohort, overall response rate is defined as CR, VGPR and PR (partial response).	During zanubrutinib treatment, up to 5 years
WM Cohort: Best overall response rate (ORR)	For the WM cohort, best overall response rate is defined as CR, VGPR, PR (partial response), MR (minor response), SD (stable disease) or PD (progressive disease).	During zanubrutinib treatment, up to 5 years
CLL Cohort: Overall response rate (ORR)	For the CLL cohort, overall response rate is defined as CR and PR.	During zanubrutinib treatment, up to 5 years
CLL Cohort: Best overall response rate (ORR)	For the CLL cohort, best overall response rate is defined as CR, PR, SD or PD.	During zanubrutinib treatment, up to 5 years
MZL Cohort: Overall response rate (ORR)	For the MZL cohort, overall response rate is defined as CR, pMRD (probable minimal residue disease), PR and rRD (responding residual disease).	During zanubrutinib treatment, up to 5 years
MZL Cohort: Best overall response rate (ORR)	For the MZL cohort, best overall response rate is defined as CR, pMRD, PR, rRD, No change/SD or PD	During zanubrutinib treatment, up to 5 years
WM Cohort: Change of IgM levels until end of zanubrutinib treatment	Difference between the baseline value and the end of treatment value of the IgM level.	Baseline and end of zanubrutinib treatment, up to 5 years
Frequency for concomitant medication during zanubrutinib treatment	Substances (WHO-ATC level 2), ongoing status and indication (frequencies)	During zanubrutinib treatment, up to 5 years
FL Cohort: Overall response rate (ORR)	For the FL cohort, overall response rate is defined as CR or PR.	During zanubrutinib treatment, up to 5 years
FL Cohort: Best overall response rate (ORR)	For the FL cohort, best overall response rate is defined as CR, PR, MR, SD or PD.	During zanubrutinib treatment, up to 5 years
Time from first diagnosis of WM, CLL, MZL or FL to zanubrutinib treatment start	Time from first diagnosis of WM, CLL, MZL or FL to zanubrutinib treatment start including timing and duration of possible watch & wait strategy.	Baseline
Previous therapies	Key details of previous therapies (including plasmapheresis for WM, transplantations for WM, CLL and FL, radiotherapy for CLL, MZL and FL and surgery for CLL, MZL and FL).	Baseline
Daily dose of zanubrutinib	Frequency tables including the daily dose (mg) will be given using descriptive statistics.	During zanubrutinib treatment, up to 5 years
FL cohort: Daily dose of obinutuzumab	Frequency tables including the daily dose (mg) will be given using descriptive statistics.	During zanubrutinib treatment, up to 5 years
Dose modifications of zanubrutinib	Frequency tables will be provided including therapy modifications (reduction and increase) with reasons using descriptive statistics.	During zanubrutinib treatment, up to 5 years
FL cohort: Dose modifications of obinutuzumab	Frequency tables will be provided including therapy modifications (reduction and increase) with reasons using descriptive statistics.	During zanubrutinib treatment, up to 5 years
Therapy interruptions of zanubrutinib	Frequency tables will be provided including treatment interruptions with reasons as well as reasons for treatment termination.	During zanubrutinib treatment, up to 5 years
FL cohort: Therapy interruptions of obinutuzumab	Frequency tables will be provided including treatment interruptions with reasons as well as reasons for treatment termination.	During zanubrutinib treatment, up to 5 years
Dose intensity of zanubrutinib	Frequency tables will be provided including the dose intensity (absolute and relative) using descriptive statistics.	During zanubrutinib treatment, up to 5 years
FL cohort: Dose intensity of obinutuzumab	Frequency tables will be provided including the dose intensity (absolute and relative) using descriptive statistics.	During zanubrutinib treatment, up to 5 years
Treatment duration with zanubrutinib	Frequency tables will be provided including the treatment duration will be given using descriptive statistics.	During zanubrutinib treatment, up to 5 years
FL cohort: Treatment duration with obinutuzumab	Frequency tables will be provided including the treatment duration will be given using descriptive statistics.	During zanubrutinib treatment, up to 5 years
Subsequent antineoplastic therapies	Key details of subsequent antineoplastic therapies after zanubrutinib (including plasmapheresis for WM, stem cell transplantations for WM, CLL and FL, radiotherapy for CLL, MZL and FL and surgery for CLL, MZL and FL): duration (descriptive statistics), number, substances and reason for end of subsequent treatments (frequencies).	End of zanubrutinib treatment until end of study, up to 5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patients' treatment expectation and satisfaction	Patients' treatment expectation and satisfaction (assessed via project specific questionnaire) will be analyzed by time point, using absolute and relative frequencies.	Baseline, 3 months after treatment start with zanubrutinib, end of treatment
Physicians' treatment expectation and satisfaction	Physicians' treatment expectation and satisfaction (assessed via project specific questionnaire) will be analyzed by time point, using absolute and relative frequencies.	Baseline, 3 months after treatment start with zanubrutinib, end of treatment
Patient management during SARS-Covid-19 pandemic	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.	Baseline and end of zanubrutnib treatment, up to 5 years
Collection of biomarker test results (according to clinical routine)	Number of patients with biomarker testing as well as sample types, test methods and test results of biomarker testing per biomarker will be provided including patients with resistance mechanism testing before treatment decision with zanubrutinib. Information on the testing of MYD88 and CXCR4 is mandatory.	Baseline, up to 5 years

Collaborators and Investigators

• Sponsor: iOMEDICO AG
• Collaborators: 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 record dates

Study Major Dates

• Study Start (Actual): April 26, 2022
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: March 23, 2022
• First Submitted That Met QC Criteria: April 5, 2022
• First Posted (Actual): April 13, 2022

Study Record Updates

• Last Update Posted (Estimated): December 8, 2023
• Last Update Submitted That Met QC Criteria: December 4, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Follicular Lymphoma; Marginal Zone Lymphoma; Chronic Lymphocytic Leukemia; Zanubrutinib; Waldenström's Macroglobulinemia; Brukinsa
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Disease Attributes; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Neoplasms, Plasma Cell; Leukemia, B-Cell; Lymphoma, B-Cell; Chronic Disease; Lymphoma; Lymphoma, Follicular; Leukemia; Lymphoma, B-Cell, Marginal Zone; Waldenstrom Macroglobulinemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Obinutuzumab; Zanubrutinib
• Other Study ID Numbers: IOM-100461

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No