Acalabrutinib Real World Italian obSErvational Study -ARISE (ARISE)

Acalabrutinib Real World Italian obSErvational Secondary Data Collection Study of Acalabrutinib in the Treatment of Patients With Chronic Lymphocytic Leukemia.

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Lymphocytic Leukemia
• Intervention / Treatment: Drug: acalabrutinib

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.

• Study Type: Observational
• Enrollment (Actual): 151

Contacts and Locations

Study Locations

• Italy
  • Alessandria, Italy, 15121
    • Research Site
  • Ancona, Italy, 60126
    • Research Site
  • Bari, Italy, 70124
    • Research Site
  • Barletta, Italy, 76121
    • Research Site
  • Brindisi, Italy, 72100
    • Research Site
  • Campobasso, Italy, 86100
    • Research Site
  • Catania, Italy, 95100
    • Research Site
  • Catanzaro, Italy, 88100
    • Research Site
  • Cosenza, Italy, 87100
    • Research Site
  • Crema, Italy, 26013
    • Research Site
  • Cuneo, Italy, 12100
    • Research Site
  • Foggia, Italy, 71122
    • Research Site
  • Frosinone, Italy, 03100
    • Research Site
  • Genova, Italy, 16132
    • Research Site
  • Lecce, Italy, 73100
    • Research Site
  • Messina, Italy, 98158
    • Research Site
  • Milan, Italy, 20122
    • Research Site
  • Milan, Italy, 20132
    • Research Site
  • Monza, Italy, 20900
    • Research Site
  • Naples, Italy, 80131
    • Research Site
  • Padova, Italy, 35128
    • Research Site
  • Pagani, Italy, 84016
    • Research Site
  • Perugia, Italy, 06132
    • Research Site
  • Pescara, Italy, 65124
    • Research Site
  • Ravenna, Italy, 48121
    • Research Site
  • Reggio Calabria, Italy, 89133
    • Research Site
  • Roma, Italy, 00168
    • Research Site
  • Roma, Italy, 00189
    • Research Site
  • Roma, Italy, 00161
    • Research Site
  • Roma, Italy, 00133
    • Research Site
  • Roma, Italy, 00184
    • Research Site
  • Rozzano, Italy, 20089
    • Research Site
  • Salerno, Italy, 84078
    • Research Site
  • San Giovanni Rotondo, Italy, 71013
    • Research Site
  • Torino, Italy, 10126
    • Research Site
  • Torino, Italy, 10154
    • Research Site
  • Torino, Italy, 10043
    • Research Site
  • Torino, Italy, 10073
    • Research Site
  • Tricase, Italy, 73039
    • Research Site
  • Varese, Italy, 21100
    • Research Site
  • Viterbo, Italy, 01100
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• 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.

Description

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.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
time to acalabrutinib discontinuation	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.	through study completion, an average of 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
demographic and clinical characteristics of CLL patients treated with acalabrutinib	To describe demographic and clinical characteristics of CLL patients treated with acalabrutinib, by treatment line and potential associations with acalabrutinib permanent discontinuation.	baseline
describe acalabrutinib treatment patterns	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 )initiation	through study completion, an average of 5 years
CLL clinical stage	according to Binet staging system (stage A, B, C) according to Eichhorst et al., 2020.	baseline
FISH profile	del(11q) del(17p); trisomy 12; del(13q); normal	baseline
Date of birth	month/year	baseline
gender	male or famale	baseline
Height	cm	baseline
Weight	Kg	throught study completion, an average of 5 years
Body Mass Index	kg/m2	Through study completion, an average of 5 years
Medical illness burden	CIRS-G scale	Through study completion, an average of 5 years
Red blood cell count	x10^12/L	Through study completion, an average of 5 years
White blood cell count	x10^9/L	Through study completion, an average of 5 years
platelets count	x10^9/L	Through study completion, an average of 5 years
hemoglobin	gr/dL	Through study completion, an average of 5 years
differential count of lymphocytes and neutrophils		Through study completion, an average of 5 years
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
measure effectiveness of acalabrutinib	To measure effectiveness of acalabrutinib treatment in patients with CLL in terms of: Progression Free Survival (PFS), Overall Survival (OS), Overall Response Rate (ORR - categorization according to iwCLL), Time To Next Treatment (TTNT) Kaplan-Meier median time to progression (defined as time from start date of acalabrutinib treatment to the first assessment of disease progression) Kaplan-Meier median time to Death (defined as time from start date of acalabrutinib treatment to death) Proportion of patients with Complete Response, Partial response, Partial Response with lymphocytosis or Stable Disease Kaplan-Meier median time to next treatment (defined as time from start date of acalabrutinib treatment to the first consecutive treatment)	through study completion, an average of 5 years
evaluate effectiveness of CLL treatments following acalabrutinib discontinuation	To evaluate effectiveness of CLL treatments following acalabrutinib discontinuation in terms of PFS2, OS and ORR by treatment and relative causes of discontinuation. Kaplan-Meier median time to progression (defined as time from start date of acalabrutinib treatment to progression) on next-line treatment The time to death and the overall response are computed as described for the exploratory objective n.1 Proportion of each reason for discontinuation of CLL treatments following acalabrutinib (patient's decision, physician's choice, adverse events, death, other, unknown)	through study completion, an average of 5 years
estimate Healthcare Resources Utilization	To estimate Healthcare Resources Utilization by patients with CLL, in terms of hospitalizations and visits (routine follow-up, outpatient visits and emergency visits) Total visits= number of all visits performed during the observation period Total hospitalizations= number of all hospitalizations performed during the observation period Mean, minimum and maximum total visits Mean, minimum and maximum total hospitalizations Mean, minimum and maximum hospitalizations duration In case of visits and hospitalization due to AE suspected of relationship with acalabrutinib (ADR): proportion of each type of adverse event.	through study completion, an average of 5 years

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Yghea
• Investigators: Principal Investigator: Carola Boccomini, AOU Città della Salute e della Scienza di Torino - Presidio Molinette; Principal Investigator: Chiara Borrella, IRCCS San Gerardo Monza; Principal Investigator: Catello Califano, PO A. TORTORA; Principal Investigator: Daniele Caracciolo, AOU Mater Domini / Università Magna Grecia; Principal Investigator: Gioacchino Catania, AO SS Antonio e Biagio e Cesare Arrigo; Principal Investigator: Marta Coscia, AOU Città della Salute e della Scienza; Principal Investigator: Luigi Curreli, PO San Martino; Principal Investigator: Giovanni D'Arena, PO S.Luca - DEA I livello; Principal Investigator: Federica De Marco, Ospedale San Giovanni Bosco, ASL Città di Torino; Principal Investigator: Gaetano De Santis, Ospedale "Mon. Dimiccoli" Barletta; Principal Investigator: Nicola Di Renzo, PO Vito Fazzi ASL di Lecce; Principal Investigator: Ambra Di Veroli, ASL Viterbo; Principal Investigator: Amalia Stefania Figuera, AOU Policlinico G.Rodolico - San Marco; Principal Investigator: Myriam Foglietta, AO S. Croce e Carle; Principal Investigator: Vincenzo Fraticelli, Responsible Research Hospital; Principal Investigator: Susanna Gallo, ASLTO4 Sedi di Ciriè - Chivasso ed Ivrea; Principal Investigator: Massimo Gentile, AO Cosenza; Principal Investigator: Giulio Giordano, Ospedale di riferimento regionale "A. Cardarelli" - Campobasso; Principal Investigator: Luca Laurenti, Policlinico Universitario Gemelli IRCCS; Principal Investigator: Massimo Magagnoli, Istituto Clinico Humanitas; Principal Investigator: Luigi Malandruccolo, Ospedale Spaziani - ASL Frosinone; Principal Investigator: Alessandro Noto, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico; Principal Investigator: Francesca Romana Mauro, Università Sapienza di Roma; Principal Investigator: Carla Minoia, IRCCS Giovanni Paolo II; Principal Investigator: Roberta Murru, Ospedale Oncologico" A. Businco" - ARNAS "G. Brotzu"; Principal Investigator: Pellegrino Musto, Aou Policlinico Consorziale Di Bari; Principal Investigator: Marco De Gobbi, Aou San Luigi Gonzaga; Principal Investigator: Getano Palumbo, Ospedali Riuniti di Foggia; Principal Investigator: Maria Cristina Pasquini, Ospedale Maggiore Crema; Principal Investigator: Domenico Pastore, PO "A.Perrino" di Brindisi; Principal Investigator: Elsa Pennese, ASL Pescara; Principal Investigator: Rosario Potito Scalzulli, IRCCS Casa Sollievo della Sofferenza; Principal Investigator: Lydia Scarfò, IRCCS Ospedale San Raffaele; Principal Investigator: Ilaria Scortechini, Aou Delle Marche; Principal Investigator: Paolo Sportoletti, Università degli Studi di Perugia - Azienda Ospedaliera S.M. Perugia; Principal Investigator: Caterina Cecilia Stelitano, Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli; Principal Investigator: Agostino Tafuri, AOU Sant'Andrea; Principal Investigator: Anna Tamburini, Azienda Ospedaliera S. Giovanni Addolorata; Principal Investigator: Monica Tani, Ospedale Santa Maria delle Croci - Ravenna; Principal Investigator: Vincenzo Pavone, Azienda Ospedaliera Cardinale G. Panico; Principal Investigator: Andrea Visentin, Azienda Ospedale Universita Padova; Principal Investigator: Massimiliano Postorino, Ospedale Policlinico Tor Vergata; Principal Investigator: Laura Nocilli, Ospedale Papardo; Principal Investigator: Fabrizio Pane, Federico II University; Principal Investigator: Marina Motta, Asst Degli Spedali Civili Di Brescia; Principal Investigator: Adalberto Ibatici, Ospedale Policlinico San Martino

Study record dates

Study Major Dates

• Study Start (Actual): August 8, 2023
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): April 30, 2027

Study Registration Dates

• First Submitted: July 6, 2023
• First Submitted That Met QC Criteria: January 3, 2024
• First Posted (Actual): January 16, 2024

Study Record Updates

• Last Update Posted (Actual): April 23, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Observational; CLL; Chronic Lymphocytic Leukemia; acalabrutinib
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Leukemia, Lymphocytic, Chronic, B-Cell; Tyrosine Kinase Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; acalabrutinib
• Other Study ID Numbers: D8221R00002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.