AN ITALIAN RETROSPECTIVE-PROSPECTIVE OBSERVATIONAL STUDY ON THE USE OF ZANUBRUTINIB IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA (AZALEA)

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Effectiveness study (incl. comparative)

  Safety study (incl. comparative)
• Data collection methods:
  Primary data collection

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Name of medicine:
  BRUKINSA
• Name of medicine, other:
  BGB-3111
• Study drug International non-proprietary name (INN) or common name:
  ZANUBRUTINIB
• Medical condition to be studied:
  Chronic lymphocytic leukaemia

  Chronic lymphocytic leukaemia refractory
• Additional medical condition(s):
  treatment-naive chronic lymphocytic leukaemia, relapsed or refractory chronic lymphocytic leukaemia

Population studied

• Short description of the study population:
  Cohort A: patients with CLL who were enrolled and treated as part of the BeiGene Compassionate Use Program and legislative decree on compassionate uses (7 September 2017).; ; Cohort B: patients with a confirmed diagnosis of CLL per the iwCLL criteria, TN or R/R, who were prescribed zanubrutinib in clinical practice, based on the standard of care criteria at the practice. A prescription for zanubrutinib must precede the patient’s signature on the informed consent form.
• Age groups:
  Adult and elderly population (≥18 years)

  Elderly (≥ 65 years)
• Estimated number of subjects:
  250

Study design details

• Study design:
  The study will be conducted as a retrospective/prospective design.; Cohort A: Retrospective and prospective data collection; Cohort B: Prospective data collection
• Main study objective:
  The purposes of this study are to assess: The persistency of zanubrutinib treatment; the clinical characteristics of patients initiating treatment with zanubrutinib, the clinical outcomes of patients treated with zanubrutinib; and the safety of zanubrutinib when administered to patients with TN or R/R CLL. The primary endpoint is time to permanent discontinuation (TTD) of treatment with zanubrutinib.
• Outcomes:
  Primary: Time to permanent discontinuation (TTD) of treatment with zanubrutinib; ; Secondary:; • Reasons for permanent discontinuations of treatment with zanubrutinib; • Rate of discontinuations of zanubrutinib due to adverse events; • Cumulative incidence of treatment discontinuation according to reasons (i.e. PD, AEs, etc); • Modality of treatment with zanubrutinib (daily dose and regimen of administration, i.e. QD and BID), dose reduction and rate of permanent dose reduction; • Overall survival (OS) and survival at predetermined time points (months, 6, 12, 18, 24, end of study); • Progression-free survival (PFS) by Kaplan-Meier method; • Response rate (iwCLL criteria); • Health resource utilization during the study: number and rates of hospitalizations, emergency room attendance, unscheduled visits; • Adherence to treatment (PROMIS questionnaire) at predetermined time points (months 3, 6, 9,12, 18, 24, and every six months thereafter until end of treatment - EOT); • Changes from baseline in patient-reported outcomes measured by the Global health status/QoL (GHS) and physical and role functioning scales of EORTC QLQC30, and symptom burden and fatigue scales of EORTC QLQ-CCL17 at predetermined time points (months 3, 6, 9, 12, 18, 24, and every six months thereafter until EOT); • Rate of adverse drug reactions to zanubrutinib; • Rate of serious and not serious adverse events (related and not related to zanubrutinib); • Changes in concomitant medications
• Data analysis plan:
  Data from all patients who signed the informed consent will be used in the analysis. All statistical analyses will be performed using all data collected in the database up to the data cutoff date.; ; The patient disposition will be summarized from the evaluable analysis set. The reason for discontinuation will be summarized. Unless otherwise specified, the analysis will be based on the evaluable analysis set. Data will be; summarized overall and by cohort (cohort A and cohort B).; ; Quantitative data will be described by standard descriptive statistics (eg, mean, standard deviation, minimum, and maximum), and qualitative data will be summarized by frequency tables with number and proportion in each category. A missing category will be included as applicable.; ; For categorical endpoints, number and proportion of patients for each category will be summarized.; ; Time-to-event endpoints, i.e. time to permanent discontinuation of zanubrutinib, OS and PFS, will be summarized graphically using Kaplan-Meier plots overall and for each cohort.; ; Two interim analyses are planned for this study. The first interim analysis will be performed in the retrospective part of cohort A, and the second interim analysis will be performed in the prospective part of cohort A and cohort B, at 6 months after the last prospective patient enrolled.