Chronic Lymphocytic Leukemia, Follicular Lymphoma, Marginal Zone Lymphoma, Waldenström's Macroglobulinemia
Conditions
Keywords
Waldenström's Macroglobulinemia, Zanubrutinib, Brukinsa, Chronic Lymphocytic Leukemia, Marginal Zone Lymphoma, Follicular Lymphoma
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.
Interventions
DRUGZanubrutinib
according to the Summary of Product Characteristics (SmPC).
DRUGObinutuzumab
according to the Summary of Product Characteristics (SmPC).
Sponsors
iOMEDICO AG
BeOne Medicines I GmbH
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Medical resource utilization | During zanubrutinib treatment, up to 6.3 years | Frequency of hospitalizations, i.e. number of hospital stays plus number of emergency unit visits (without hospitalization) per patient |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| WM Cohort: Best overall response rate (ORR) | During zanubrutinib treatment, up to 6.3 years | 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). |
| CLL Cohort: Overall response rate (ORR) | During zanubrutinib treatment, up to 6.3 years | For the CLL cohort, overall response rate is defined as CR and PR. |
| CLL Cohort: Best overall response rate (ORR) | During zanubrutinib treatment, up to 6.3 years | For the CLL cohort, best overall response rate is defined as CR, PR, SD or PD. |
| MZL Cohort: Overall response rate (ORR) | During zanubrutinib treatment, up to 6.3 years | For the MZL cohort, overall response rate is defined as CR, pMRD (probable minimal residue disease), PR and rRD (responding residual disease). |
| MZL Cohort: Best overall response rate (ORR) | During zanubrutinib treatment, up to 6.3 years | For the MZL cohort, best overall response rate is defined as CR, pMRD, PR, rRD, No change/SD or PD |
| FL Cohort: Overall response rate (ORR) | During zanubrutinib treatment, up to 6.3 years | For the FL cohort, overall response rate is defined as CR or PR. |
| FL Cohort: Best overall response rate (ORR) | During zanubrutinib treatment, up to 6.3 years | For the FL cohort, best overall response rate is defined as CR, PR, MR, SD or PD. |
| Time to treatment failure (TTF) | Treatment start with zanubrutinib until end of treatment, up to 6.3 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 6.3 years | The number of patients receiving blood product transfusion, the number of transfusions per patient and the kind of transfusion (e.g., erythrocytes, thrombocytes). |
| WM Cohort: Change of IgM levels until end of zanubrutinib treatment | Baseline and end of zanubrutinib treatment, up to 6.3 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, CLL, MZL or FL to zanubrutinib treatment start | Baseline | Time from first diagnosis of WM, CLL, MZL or FL to zanubrutinib treatment start including timing and duration of possible watch \& wait strategy. |
| Previous therapies | Baseline | 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). |
| Daily dose of zanubrutinib | During zanubrutinib treatment, up to 6.3 years | Frequency tables including the daily dose (mg) will be given using descriptive statistics. |
| FL cohort: Daily dose of obinutuzumab | During zanubrutinib treatment, up to 6.3 years | Frequency tables including the daily dose (mg) will be given using descriptive statistics. |
| Dose modifications of zanubrutinib | During zanubrutinib treatment, up to 6.3 years | Frequency tables will be provided including therapy modifications (reduction and increase) with reasons using descriptive statistics. |
| FL cohort: Dose modifications of obinutuzumab | During zanubrutinib treatment, up to 6.3 years | Frequency tables will be provided including therapy modifications (reduction and increase) with reasons using descriptive statistics. |
| Therapy interruptions of zanubrutinib | During zanubrutinib treatment, up to 6.3 years | Frequency tables will be provided including treatment interruptions with reasons as well as reasons for treatment termination. |
| FL cohort: Therapy interruptions of obinutuzumab | During zanubrutinib treatment, up to 6.3 years | Frequency tables will be provided including treatment interruptions with reasons as well as reasons for treatment termination. |
| Dose intensity of zanubrutinib | During zanubrutinib treatment, up to 6.3 years | Frequency tables will be provided including the dose intensity (absolute and relative) using descriptive statistics. |
| FL cohort: Dose intensity of obinutuzumab | During zanubrutinib treatment, up to 6.3 years | Frequency tables will be provided including the dose intensity (absolute and relative) using descriptive statistics. |
| Treatment duration with zanubrutinib | During zanubrutinib treatment, up to 6.3 years | Frequency tables will be provided including the treatment duration will be given using descriptive statistics. |
| FL cohort: Treatment duration with obinutuzumab | During zanubrutinib treatment, up to 6.3 years | Frequency tables will be provided including the treatment duration will be given using descriptive statistics. |
| 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 6.3 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 6.3 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 6.3 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 6.3 years | The proportion of patients with a best overall response of CR or VGPR. |
| In the WM cohort only: Major response rate (MRR) | During zanubrutinib treatment, up to 6.3 years | MRR is defined as the proportion of patients with a best overall response ≥ PR (partial response) |
| In the WM cohort only: Best response | During zanubrutinib treatment, up to 6.3 years | Best response is defined as best reported response during study treatment CR (complete response) or VGPR (very good partial response). |
| In the WM cohort only: IgM levels | During zanubrutinib treatment, up to 6.3 years | Change of IgM levels until end of zanubrutinib treatment for WM cohort. |
| Progression-free Survival (PFS) | Treatment start with zanubrutinib until end of study, up to 6.3 years | PFS is defined as the time from treatment start until progression or death from any cause, whichever comes first. |
| 6-, 12-, 18- 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 6.3 years | OS is defined as the time from treatment start until death. |
| 6-, 12-, 18- 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. |
| Subsequent antineoplastic therapies | End of zanubrutinib treatment until end of study, up to 6.3 years | 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). |
| Frequency for concomitant medication during zanubrutinib treatment | During zanubrutinib treatment, up to 6.3 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 6.3 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 6.3 years | Proportion of patients taking at least one-time antibiotics for treatment of AEs during zanubrutinib treatment. |
| WM Cohort: Overall response rate (ORR) | During zanubrutinib treatment, up to 6.3 years | For the WM cohort, overall response rate is defined as CR, VGPR and PR (partial response). |
| Frequency of antibiotic use in patients with neutropenia during zanubrutinib treatment | During zanubrutinib treatment, up to 6.3 years | Proportion of patients presenting with neutropenia during zanubrutinib treatment taking at least one-time antibiotics. |
Countries
Austria, Germany
Contacts
CONTACTDaniel Kummer, Dr.
PRINCIPAL_INVESTIGATORJens Kisro, Dr.
Lübecker Onkologische Schwerpunktpraxis
PRINCIPAL_INVESTIGATORRichard Greil, Prof.
Universitätsklinikum Salzburg, Klinik für Innere Medizin III
Outcome results
None listed