Acalabrutinib Real World Italian obSErvational Study -ARISE
- Conditions
- Chronic Lymphocytic Leukemia
- Registration Number
- NCT06205498
- Lead Sponsor
- AstraZeneca
- Brief Summary
Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in the adults in the Western world, with an annual incidence of approximately 5 cases per 100,000 inhabitants in Italy.
Acalabrutinib (CalquenceTM), a selective second-generation Bruton Tyrosine Kinase (BTK) inhibitor developed by AstraZeneca, has been assessed for the treatment of CLL in three phase III clinical trials, ELEVATE-TN (treatment-naïve CLL), ASCEND and ELEVATE R/R (relapsed and refractory CLL). These pivotal randomized clinical trials established the efficacy and safety of acalabrutinib in patients with CLL and based on these data CalquenceTM received EMA approval in November 2020 for the treatment of CLL in adult patients and received AIFA (Agenzia Italiana del Farmaco) reimbursement as monotherapy in December 2021. However, further data are still required to evaluate the use of acalabrutinib in the real-life conditions of post-marketing authorization.
The primary aim of ARISE study is to evaluate the time to treatment discontinuation and reasons for discontinuation for acalabrutinib in a real world setting of patients with CLL. This study will provide the first real-world data on the use of acalabrutinib in the treatment of CLL in Italy.
- Detailed Description
Study design:
This is an Italian non-interventional / observational, multicenter, longitudinal secondary data usage study based on a retrospective cohort of patients with CLL, who initiated treatment with acalabrutinib between 1st May 2021 and 30th April 2022 (index date), regardless of the treatment status at the time of inclusion. Each patient will be followed-up up to 5 years since the last enrolled patient index date (therefore for a maximum of 72 months). Five data extraction timepoints are planned for the investigators to proceed with secondary data extraction from patients' medical records and data entry into the electronic case report form (eCRFs).
Data Source(s):
Source documents (paper or electronic) are those in which patient data are recorded and documented for the first time as part of patients' path of care (e.g., patient's hospital records, pharmacy dispensing records).
A standardized, validated eCRF will be developed to capture data extracted from source documents at each participating site.
Study Population:
All consecutive adult patients with CLL who initiated treatment with acalabrutinib over the period between 1st May 2021 and 30th April 2022, according to Italian legislation dlg 219/2006 art.125.
Outcome(s):
The primary outcome is the time to acalabrutinib discontinuation (defined as time in days from start date of acalabrutinib treatment to end date of acalabrutinib treatment).
Secondary outcomes include: Time from diagnosis to start of acalabrutinib, immunophenotype, CLL clinical stage (Binet), FISH profile, mutations, karyotype, CLL treatments before acalabrutinib, socio-demographic characteristics at baseline, medical history, concomitant treatments, COVID-19 prophylaxis and treatments, constitutional symptoms, patient clinical status, ECG/TTE, complete blood count with differential, serum chemistry, HIV and Hepatitis serology, active haemolysis, time to acalabrutinib discontinuation, acalabrutinib treatment (dosage, relative changes, temporary interruption/permanent discontinuation).
Exploratory outcomes include: Time to progression, Time to death, CLL status (according to iwCLL), Time to Next Treatment, Time to progression on next line treatment, reasons for ending of CLL treatments following acalabrutinib discontinuation, visits and hospitalizations due to CLL or suspected ADR during acalabrutinib treatment.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 190
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method time to acalabrutinib discontinuation through study completion, an average of 5 years The primary outcome is the time to acalabrutinib discontinuation (defined as time in days from start date of acalabrutinib treatment to end date of acalabrutinib treatment) Kaplan-Meier median time to acalabrutinib discontinuation (defined as time in days from start date of acalabrutinib treatment to end date of acalabrutinib treatment).
(Note: Any acalabrutinib treatment suspension \>28 days is defined as discontinuation.
Any acalabrutinib treatment suspension ≤ 28 days is defined as interruption and should not be considered for the analysis of the primary objective.
- Secondary Outcome Measures
Name Time Method demographic and clinical characteristics of CLL patients treated with acalabrutinib baseline To describe demographic and clinical characteristics of CLL patients treated with acalabrutinib, by treatment line and potential associations with acalabrutinib permanent discontinuation.
FISH profile baseline del(11q) del(17p); trisomy 12; del(13q); normal
differential count of lymphocytes and neutrophils Through study completion, an average of 5 years Height baseline cm
Weight throught study completion, an average of 5 years Kg
Body Mass Index Through study completion, an average of 5 years kg/m2
describe acalabrutinib treatment patterns through study completion, an average of 5 years Duration of acalabrutinib suspension= time from the date of last dose before suspension to the date of acalabrutinib restart.
Frequency of acalabrutinib interruptions Time to interruption= time from the first dose of acalabrutinib to the date of last dose before interruption Proportion of each reason for treatment ending (adverse events, disease progression, compliance issues, patient's decision, physician's choice, death, other) In case of discontinuation for adverse event: proportion of each type of adverse event.
Frequency of acalabrutinib dose changes Proportion of each reason for dose change Time to dose change= time from the first dose of acalabrutinib to the first dose administered at the new dosage Mean dose at last acalabrutinib use Relative dose intensity= received dose/prescribed dose (where received dose is the total dose actually received by patient during the whole observation period; prescribed dose is the dose at the acalabrutinib )initiationCLL clinical stage baseline according to Binet staging system (stage A, B, C) according to Eichhorst et al., 2020.
Date of birth baseline month/year
Red blood cell count Through study completion, an average of 5 years x10\^12/L
gender baseline male or famale
Medical illness burden Through study completion, an average of 5 years CIRS-G scale
White blood cell count Through study completion, an average of 5 years x10\^9/L
platelets count Through study completion, an average of 5 years x10\^9/L
hemoglobin Through study completion, an average of 5 years gr/dL
creatinine clearance (mL/min), aspartate transaminase (AST; U/L), alanine transaminase (ALT; U/L), gamma-glutamyl transferase (GGT; U/L), bilirubin (mg/dL), LDH (U/L), β2-microglobulin (mg/dL), IgG, IgA, IgM levels (mg/dL) baseline Anti-HIV antibodies test and Hepatitis serology tests including hepatitis B surface antigen (HbsAg), hepatitis B surface antibody (HbsAb), hepatitis B core antibody (anti-HBc), and hepatitis C (HCV) antibody baseline
Trial Locations
- Locations (1)
Research Site
🇮🇹Viterbo, Italy