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NCT Number: NCT06205498

Acalabrutinib Real World Italian obSErvational Study -ARISE

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.

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Key information

Conditions

Chronic Lymphocytic Leukemia Chronic Disease Disease Attributes Hematologic Diseases Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Leukemia Leukemia, B-Cell Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Lymphoid Lymphatic Diseases Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Research Site, Alessandria, Italy

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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:

  • Age ≥ 18 years old at the date of consent subscription.
  • Diagnosis of CLL.
  • Treatment of CLL with acalabrutinib at physician's discretion initiated between 1st May 2021 and 30th April 2022.
  • 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:

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

Treatment and study plan

Acalabrutinib

Drug

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

Other names: Calquence

Primary outcomes

  1. time to acalabrutinib discontinuation

    Time frame: 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 outcomes

  1. demographic and clinical characteristics of CLL patients treated with acalabrutinib

    Time frame: baseline

    To describe demographic and clinical characteristics of CLL patients treated with acalabrutinib, by treatment line and potential associations with acalabrutinib permanent discontinuation.

  2. describe acalabrutinib treatment patterns

    Time frame: 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 )initiation

  3. CLL clinical stage

    Time frame: baseline

    according to Binet staging system (stage A, B, C) according to Eichhorst et al., 2020.

  4. FISH profile

    Time frame: baseline

    del(11q) del(17p); trisomy 12; del(13q); normal

  5. Date of birth

    Time frame: baseline

    month/year

  6. gender

    Time frame: baseline

    male or famale

  7. Height

    Time frame: baseline

    cm

  8. Weight

    Time frame: throught study completion, an average of 5 years

    Kg

  9. Body Mass Index

    Time frame: Through study completion, an average of 5 years

    kg/m2

  10. Medical illness burden

    Time frame: Through study completion, an average of 5 years

    CIRS-G scale

  11. Red blood cell count

    Time frame: Through study completion, an average of 5 years

    x10^12/L

  12. White blood cell count

    Time frame: Through study completion, an average of 5 years

    x10^9/L

  13. platelets count

    Time frame: Through study completion, an average of 5 years

    x10^9/L

  14. hemoglobin

    Time frame: Through study completion, an average of 5 years

    gr/dL

  15. differential count of lymphocytes and neutrophils

    Time frame: Through study completion, an average of 5 years

  16. 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)

    Time frame: baseline

  17. 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

    Time frame: baseline

Other outcomes

  1. measure effectiveness of acalabrutinib

    Time frame: through study completion, an average of 5 years

    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)

  2. evaluate effectiveness of CLL treatments following acalabrutinib discontinuation

    Time frame: through study completion, an average of 5 years

    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)

  3. estimate Healthcare Resources Utilization

    Time frame: through study completion, an average of 5 years

    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.

Sponsors and collaborators

Lead sponsor

AstraZeneca

Industry

Collaborators

  • Yghea

Registry information

Official study title

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

Acronym: ARISE

Important dates

Study start
2023
Primary completion
2027
Study completion
2027
First posted
Jan 16, 2024
Registry last updated
Apr 23, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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