Clinical trial NCT06205498: Acalabrutinib Real World Italian obSErvational Study -ARISE
Official title: Acalabrutinib Real World Italian obSErvational Secondary Data Collection Study of Acalabrutinib in the Treatment of Patients With Chronic Lymphocytic Leukemia.
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Chronic Lymphocytic Leukemia
Keywords: Chronic Lymphocytic Leukemia
acalabrutinib
CLL
Observational
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Yghea
First posted: 2024-01-16
Enrollment: 190
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Investigators participating in this observational study should include all patients with CLL who initiated treatment with acalabrutinib over the period between May 1st, 2021 and April 30th, 2022, regardless of the treatment status at the time of inclusion. Thus, at the time of enrolment and retrospective data collection, patients may still be on treatment or have stopped treatment for any reason.

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.

Eligibility criteria: Inclusion Criteria All consecutive patients with CLL who received acalabrutinib according to Italian legislation dlg 219/2006 art.125 will be eligible for inclusion in the study, subject to site agreement and patient consent to participate.

Patients must meet the following criteria for study entry:

1. Age ≥ 18 years old at the date of consent subscription.
2. Diagnosis of CLL.
3. Treatment of CLL with acalabrutinib at physician's discretion initiated between 1st May 2021 and 30th April 2022.
4. Informed consent to participate in the study and privacy form signed by the patient (or their legal representative).

Exclusion Criteria

Patients who meet any of the following criteria will be excluded:

1. Acalabrutinib treatment initiation before 1st May 2021 or after 30th April 2022.

Primary outcomes:
measure: time to acalabrutinib discontinuation
timeFrame: through study completion, an average of 5 years
Secondary outcomes:
measure: demographic and clinical characteristics of CLL patients treated with acalabrutinib
timeFrame: baseline
measure: describe acalabrutinib treatment patterns
timeFrame: through study completion, an average of 5 years
measure: CLL clinical stage
timeFrame: baseline
measure: FISH profile
timeFrame: baseline
measure: Date of birth
timeFrame: baseline
measure: gender
timeFrame: baseline
measure: Height
timeFrame: baseline
measure: Weight
timeFrame: throught study completion, an average of 5 years
measure: Body Mass Index
timeFrame: Through study completion, an average of 5 years
measure: Medical illness burden
timeFrame: Through study completion, an average of 5 years
measure: Red blood cell count
timeFrame: Through study completion, an average of 5 years
measure: White blood cell count
timeFrame: Through study completion, an average of 5 years
measure: platelets count
timeFrame: Through study completion, an average of 5 years
measure: hemoglobin
timeFrame: Through study completion, an average of 5 years
measure: differential count of lymphocytes and neutrophils
timeFrame: Through study completion, an average of 5 years
measure: 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)
timeFrame: baseline
measure: 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
timeFrame: baseline
Other outcomes:
measure: measure effectiveness of acalabrutinib
timeFrame: through study completion, an average of 5 years
measure: evaluate effectiveness of CLL treatments following acalabrutinib discontinuation
timeFrame: through study completion, an average of 5 years
measure: estimate Healthcare Resources Utilization
timeFrame: through study completion, an average of 5 years
Locations:
city: Alessandria
country: Italy
facility: Research Site
city: Ancona
country: Italy
facility: Research Site
city: Bari
country: Italy
facility: Research Site
city: Barletta
country: Italy
facility: Research Site
city: Brescia
country: Italy
facility: Research Site
city: Brindisi
country: Italy
facility: Research Site
city: Cagliari
country: Italy
facility: Research Site
city: Campobasso
country: Italy
facility: Research Site
city: Catania
country: Italy
facility: Research Site
city: Catanzaro
country: Italy
facility: Research Site
city: Cosenza
country: Italy
facility: Research Site
city: Crema (Cremona)
country: Italy
facility: Research Site
city: Cuneo
country: Italy
facility: Research Site
city: Foggia
country: Italy
facility: Research Site
city: Frosinone
country: Italy
facility: Research Site
city: Genova
country: Italy
facility: Research Site
city: Lecce
country: Italy
facility: Research Site
city: Messina
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Monza
country: Italy
facility: Research Site
city: Napoli
country: Italy
facility: Research Site
city: Padova
country: Italy
facility: Research Site
city: Pagani (Salerno)
country: Italy
facility: Research Site
city: Perugia
country: Italy
facility: Research Site
city: Pescara
country: Italy
facility: Research Site
city: Ravenna
country: Italy
facility: Research Site
city: Reggio Calabria
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Rozzano (MI)
country: Italy
facility: Research Site
city: Salerno
country: Italy
facility: Research Site
city: San Giovanni Rotondo(FG)
country: Italy
facility: Research Site
city: Torino
country: Italy
facility: Research Site
city: Torino
country: Italy
facility: Research Site
city: Torino
country: Italy
facility: Research Site
city: Torino
country: Italy
facility: Research Site
city: Torino
country: Italy
facility: Research Site
city: Tricase(LE)
country: Italy
facility: Research Site
city: Varese
country: Italy
facility: Research Site
city: Viterbo
country: Italy
facility: Research Site
Study officials:
affiliation: AOU Città della salute e della scienza di Torino - Presidio Molinette
name: Carola Boccomini
role: PRINCIPAL_INVESTIGATOR
affiliation: IRCCS San Gerardo Monza
name: Chiara Borrella
role: PRINCIPAL_INVESTIGATOR
affiliation: PO A. TORTORA
name: Catello Califano
role: PRINCIPAL_INVESTIGATOR
affiliation: AOU Mater Domini / Università Magna Grecia
name: Daniele Caracciolo
role: PRINCIPAL_INVESTIGATOR
affiliation: AO SS Antonio e Biagio e Cesare Arrigo
name: Gioacchino Catania
role: PRINCIPAL_INVESTIGATOR
affiliation: AOU Città della Salute e della Scienza
name: Marta Coscia
role: PRINCIPAL_INVESTIGATOR
affiliation: PO San Martino
name: Luigi Curreli
role: PRINCIPAL_INVESTIGATOR
affiliation: PO S.Luca - DEA I livello
name: Giovanni D'Arena
role: PRINCIPAL_INVESTIGATOR
affiliation: Ospedale San Giovanni Bosco, ASL Città di Torino
name: Federica De Marco
role: PRINCIPAL_INVESTIGATOR
affiliation: Ospedale "Mon. Dimiccoli" Barletta
name: Gaetano De Santis
role: PRINCIPAL_INVESTIGATOR
affiliation: PO Vito Fazzi ASL di Lecce
name: Nicola Di Renzo
role: PRINCIPAL_INVESTIGATOR
affiliation: ASL Viterbo
name: Ambra Di Veroli
role: PRINCIPAL_INVESTIGATOR
affiliation: AOU Policlinico G.Rodolico - San Marco
name: Amalia Stefania Figuera
role: PRINCIPAL_INVESTIGATOR
affiliation: AO S. Croce e Carle
name: Myriam Foglietta
role: PRINCIPAL_INVESTIGATOR
affiliation: Responsible Research Hospital
name: Vincenzo Fraticelli
role: PRINCIPAL_INVESTIGATOR
affiliation: ASLTO4 Sedi di Ciriè - Chivasso ed Ivrea
name: Susanna Gallo
role: PRINCIPAL_INVESTIGATOR
affiliation: AO Cosenza
name: Massimo Gentile
role: PRINCIPAL_INVESTIGATOR
affiliation: Ospedale di riferimento regionale "A. Cardarelli" - Campobasso
name: Giulio Giordano
role: PRINCIPAL_INVESTIGATOR
affiliation: Ospedale Policlinico San Martino
name: Adalberto Ibatici
role: PRINCIPAL_INVESTIGATOR
affiliation: Policlinico Universitario Gemelli IRCCS
name: Luca Laurenti
role: PRINCIPAL_INVESTIGATOR
affiliation: Istituto Clinico Humanitas
name: Massimo Magagnoli
role: PRINCIPAL_INVESTIGATOR
affiliation: Ospedale Spaziani - ASL Frosinone
name: Luigi Malandruccolo
role: PRINCIPAL_INVESTIGATOR
affiliation: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
name: Alessandro Noto
role: PRINCIPAL_INVESTIGATOR
affiliation: Università Sapienza di Roma
name: Francesca Romana Mauro
role: PRINCIPAL_INVESTIGATOR
affiliation: IRCCS Giovanni Paolo II
name: Carla Minoia
role: PRINCIPAL_INVESTIGATOR
affiliation: Ospedale Oncologico" A. Businco" - ARNAS "G. Brotzu"
name: Roberta Murru
role: PRINCIPAL_INVESTIGATOR
affiliation: Asst Degli Spedali Civili Di Brescia
name: Marina Motta
role: PRINCIPAL_INVESTIGATOR
affiliation: AOU Policlinico Consorziale di Bari
name: Pellegrino Musto
role: PRINCIPAL_INVESTIGATOR
affiliation: AOU San Luigi Gonzaga
name: Marco De Gobbi
role: PRINCIPAL_INVESTIGATOR
affiliation: Ospedali Riuniti di Foggia
name: Getano Palumbo
role: PRINCIPAL_INVESTIGATOR
affiliation: Federico II University
name: Fabrizio Pane
role: PRINCIPAL_INVESTIGATOR
affiliation: Ospedale Maggiore Crema
name: Maria Cristina Pasquini
role: PRINCIPAL_INVESTIGATOR
affiliation: PO "A.Perrino" di Brindisi
name: Domenico Pastore
role: PRINCIPAL_INVESTIGATOR
affiliation: ASL Pescara
name: Elsa Pennese
role: PRINCIPAL_INVESTIGATOR
affiliation: IRCCS Casa Sollievo della Sofferenza
name: Rosario Potito Scalzulli
role: PRINCIPAL_INVESTIGATOR
affiliation: IRCCS Ospedale San Raffaele
name: Lydia Scarfò
role: PRINCIPAL_INVESTIGATOR
affiliation: AOU delle Marche
name: Ilaria Scortechini
role: PRINCIPAL_INVESTIGATOR
affiliation: Università degli Studi di Perugia - Azienda Ospedaliera S.M. Perugia
name: Paolo Sportoletti
role: PRINCIPAL_INVESTIGATOR
affiliation: Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli
name: Caterina Cecilia Stelitano
role: PRINCIPAL_INVESTIGATOR
affiliation: AOU Sant'Andrea
name: Agostino Tafuri
role: PRINCIPAL_INVESTIGATOR
affiliation: Azienda Ospedaliera S. Giovanni Addolorata
name: Anna Tamburini
role: PRINCIPAL_INVESTIGATOR
affiliation: Ospedale Santa Maria delle Croci - Ravenna
name: Monica Tani
role: PRINCIPAL_INVESTIGATOR
affiliation: Azienda Ospedaliera Cardinale G. Panico
name: Vincenzo Pavone
role: PRINCIPAL_INVESTIGATOR
affiliation: Azienda Ospedale Università Padova
name: Andrea Visentin
role: PRINCIPAL_INVESTIGATOR
affiliation: Ospedale Policlinico Tor Vergata
name: Massimiliano Postorino
role: PRINCIPAL_INVESTIGATOR
affiliation: Ospedale Papardo
name: Laura Nocilli
role: PRINCIPAL_INVESTIGATOR
References: