PICAROS - Acalabrutinib RWE on 1L CLL in Spain (PICAROS)

Non-interventional Cohort Study of Patients Previously Untreated or First-generation BTKi Intolerant With Chronic Lymphocytic Leukemia Describing the First-line Use of Acalabrutinib and Its Real-world Outcomes in Spain: the PICAROS Study

This is a multicenter non-interventional study (NIS) of patients with CLL treated with first-line acalabrutinib according to routine clinical practice in Spain. It included an initial cohort of patients who initiated treat-to-progression acalabrutinib for the first time within the year before the first site initiation visit, both for previously untreated CLL and after switching in first line from another BTK inhibitor due to intolerance in absence of progression (cohort 1). This cohort is complemented with the addition of another regarding the first-line fixed-duration acalabrutinib use with venetoclax in routine practice (cohort 2).

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Lymphocytic Leukemia

Detailed Description

This is a multicenter, non-interventional study (NIS) based on ambispective (including retrospective and/or prospective) real-world data collection of patients with CLL who received treatment with acalabrutinib for the first time in Spain.

It included an initial cohort of patients who initiated treat-to-progression acalabrutinib for the first time within the year before the first site initiation visit, both for previously untreated CLL and after switching in first line from another BTK inhibitor due to intolerance in absence of progression (cohort 1). This cohort is complemented with the addition of another regarding the first-line fixed-duration acalabrutinib use with venetoclax in routine practice (cohort 2).

For the cohort 1, the start of acalabrutinib treatment (index date) was prior to the first site initiation visit. For both cohorts 1 and 2, the clinical decision of starting patient on acalabrutinib has to independently occur prior to the patient inclusion into this study. Patients' eligibility for study inclusion is regardless of their current status of acalabrutinib therapy, for example, patients already deceased or discontinued therapy are still eligible to be included into this study. Patient data will be collected both retrospectively and/or prospectively up to approximately 32 months from the first site initiation visit for cohort 1, and approximately 25 months after the inclusion of the last patient in the cohort 2. For patients who received acalabrutinib therapy and have deceased, only retrospective medical chart review will be conducted.

• Study Type: Observational
• Enrollment (Actual): 192

Contacts and Locations

Study Locations

• Spain
  • Andalusia
    • Almería, Andalusia, Spain, 4009
      • Research Site
    • Córdoba, Andalusia, Spain, 14004
      • Research Site
    • Granada, Andalusia, Spain, 18014
      • Research Site
    • Jaén, Andalusia, Spain, 23007
      • Research Site
    • Marbella, Andalusia, Spain, 29603
      • Research Site
    • Málaga, Andalusia, Spain, 29010
      • Research Site
    • Seville, Andalusia, Spain, 41013
      • Research Site
  • Aragon
    • Zaragoza, Aragon, Spain, 50009
      • Research Site
  • Balearic Islands
    • Palma de Mallorca, Balearic Islands, Spain, 7010
      • Research Site
    • Palma de Mallorca, Balearic Islands, Spain, 7198
      • Research Site
  • Canary Islands
    • Las Palmas de Gran Canaria, Canary Islands, Spain, 35016
      • Research Site
    • Las Palmas de Gran Canaria, Canary Islands, Spain, 35019
      • Research Site
    • San Cristóbal de La Laguna, Canary Islands, Spain, 38320
      • Research Site
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Research Site
  • Castille and León
    • Salamanca, Castille and León, Spain, 37007
      • Research Site
    • Segovia, Castille and León, Spain, 40002
      • Research Site
    • Valladolid, Castille and León, Spain, 47003
      • Research Site
    • Valladolid, Castille and León, Spain, 47012
      • Research Site
  • Castille-La Mancha
    • Guadalajara, Castille-La Mancha, Spain, 19002
      • Research Site
    • Toledo, Castille-La Mancha, Spain, 45004
      • Research Site
  • Catalonia
    • Barcelona, Catalonia, Spain, 8003
      • Research Site
    • Barcelona, Catalonia, Spain, 8025
      • Research Site
    • Barcelona, Catalonia, Spain, 8035
      • Research Site
    • Barcelona, Catalonia, Spain, 8036
      • Research Site
    • Granollers, Catalonia, Spain, 8402
      • Research Site
    • L'Hospitalet de Llobregat, Catalonia, Spain, 8908
      • Research Site
    • Lleida, Catalonia, Spain, 25198
      • Research Site
    • Terrassa, Catalonia, Spain, 8221
      • Research Site
  • Galicia
    • Ourense, Galicia, Spain, 32005
      • Research Site
    • Santiago de Compostela, Galicia, Spain, 15706
      • Research Site
    • Vigo, Galicia, Spain, 36312
      • Research Site
  • Madrid
    • Madrid, Madrid, Spain, 28006
      • Research Site
    • Madrid, Madrid, Spain, 28031
      • Research Site
    • Madrid, Madrid, Spain, 28034
      • Research Site
    • Madrid, Madrid, Spain, 28040
      • Research Site
    • Madrid, Madrid, Spain, 28041
      • Research Site
    • Madrid, Madrid, Spain, 28046
      • Research Site
    • Madrid, Madrid, Spain, 28905
      • Research Site
    • Madrid, Madrid, Spain, 28911
      • Research Site
    • Majadahonda, Madrid, Spain, 28222
      • Research Site
  • Murcia
    • El Palmar, Murcia, Spain, 30120
      • Research Site
    • Murcia, Murcia, Spain, 30008
      • Research Site
  • Principality of Asturias
    • Oviedo, Principality of Asturias, Spain, 33011
      • Research Site
  • Valencia
    • Alicante, Valencia, Spain, 3010
      • Research Site
    • Valencia, Valencia, Spain, 46010
      • Research Site
    • Valencia, Valencia, Spain, 46014
      • Research Site
    • Valencia, Valencia, Spain, 46026
      • Research Site

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

The study aims to include approximately 315 patients in the cohort 1 and 103 patients in the cohort 2 who started acalabrutinib for the first time for the treatment of their CLL. To minimize selection biases, all patients (alive or deceased) identified on acalabrutinib will be eligible for inclusion into the study. These patients will be included from approximately 50 hospitals distributed throughout Spain.

Description

Inclusion Criteria:

• Age ≥18 years old at starting acalabrutinib treatment.
• Diagnosis of CLL.
• Start of acalabrutinib treatment (index date) as per the CLL SmPC:
• in treatment-naïve CLL patients or those switching in first-line between first-generation BTK inhibitor to acalabrutinib due to intolerance in absence of progression according to routine clinical practice within the year before the first site initiation visit (cohort 1).
• in treatment-naïve CLL patients for the fixed-duration treatment combination of acalabrutinib plus venetoclax (with or without obinutuzumab) according to routine clinical practice from the EMA approval (i.e., 2 June 2025) (cohort 2).

Decision to administer acalabrutinib must be made and documented prior to inclusion into the study and must follow local clinical practice.

• Informed consent (for alive patients).

Exclusion Criteria:

• Enrolled in any clinical trial during acalabrutinib treatment.
• Patients who are unable to understand the study and its questionnaires due to insufficient knowledge of the Spanish language or their health status.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Cohort 1; Patients who initiated treat-to-progression acalabrutinib for the first time within the year before the first site initiation visit as per routine clinical practice, both for previously untreated CLL and after switching in first line from another BTK inhibitor due to intolerance in absence of progression.
Cohort 2; Patients with first-line fixed-duration acalabrutinib use with venetoclax in routine clinical practice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients on acalabrutinib therapy at 24 months after treatment initiation (cohort 1).	Proportion of patients on acalabrutinib therapy at 24 months after treatment initiation (cohort 1). In addition to this outcome measured in the overall cohort, it will also be assessed by the following factors: the reason for treatment initiation (i.e., first-line treatment-naïve patients, and those switching due to intolerance in absence of progression),; presence/absence of risk factors (i.e., del17p, TP53 mutation, and unmutated IGHV).; cardiovascular comorbidities (yes/no).	24 months after treatment initiation (cohort 1).
Real-world overall response rate (rwORR) achieved until the end of the observational period for first-line fixed duration acalabrutinib therapy (cohort 2)	rwORR (i.e., the proportion of patients that achieved complete or partial response) achieved until the end of the observational period for first-line fixed-duration acalabrutinib therapy as assessed by the treating physician (cohort 2). Complete response may include complete response, complete response with incomplete marrow recovery, or unconfirmed complete response (marrow biopsy not performed). Partial response may include partial response, or partial response with lymphocytosis. The rwORR will be assessed by the treating physician in routine clinical practice, including the use or not of the 2018 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria. The end of observational period for first-line fixed-duration combinations of acalabrutinib is defined as the start date of a subsequent line therapy or study end date, whichever comes first.	From fixed-duration acalabrutinib start to the start date of a subsequent line therapy or study end date (cohort 2), assessed up to 25 months after the inclusion of the last patient in the cohort 2.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acalabrutinib±venetoclax doses (cohorts 1 and 2).	Acalabrutinib±venetoclax doses (e.g., starting does and dose adjustments), overall (cohorts 1 and 2) and by the reason for treatment initiation (i.e., first-line treatment-naïve patients, and those switching due to intolerance in absence of progression) (cohort 1 only). In cohort 2, doses (e.g., starting dose, dose adjustments, maximum dose achieved) and reasons for changes within the acalabrutinib±venetoclax fixed-duration regimen will also be described globally and for each drug separately, as well as the time to reach the maximal dose.	At start date and subsequent dose adjustments during acalabrutinib±venetoclax administration assessed up to 32 months of prospective study follow-up in the cohort 1 and 25 months after the inclusion of the last patient in the cohort 2.
Patients with acalabrutinib±venetoclax dose adjustments (n, %), temporary interruptions (n, %), and permanent discontinuations (n, %) (cohorts 1 and 2).	Acalabrutinib±venetoclax dose adjustments, temporary interruptions, and permanent discontinuations, overall (cohorts 1 and 2) and by the reason for treatment initiation (i.e., first-line treatment-naïve patients, and those switching due to intolerance in absence of progression) (cohort 1 only). In patients with regimen modifications within cohort 2, the proportion of patients with these regimen modifications and the time from treatment initiation to the regimen modification within same line therapy prior to progression (e.g., treatment duration and number of cycles prior to the modification, and reason for the modification). In cohort 2, temporary interruptions, permanent discontinuations, and their reasons for changes within the acalabrutinib±venetoclax fixed-duration regimen will also be described globally and for each drug separately, as well as the proportion of patients requiring dose reductions after achieving maximum dose.	From acalabrutinib±venetoclax start to acalabrutinib±venetoclax end, assessed up to 32 months of prospective study follow-up in the cohort 1 and 25 months after the inclusion of the last patient in the cohort 2.
Treatment duration in months (cohorts 1 and 2).	Treatment duration (cohorts 1 and 2), overall and by the reason for treatment initiation (i.e., first-line treatment-naïve patients, and those switching due to intolerance in absence of progression) (cohort 1 only). In cohort 2, also median number of completed cycles and the proportion of patients who complete 14 cycles. Baseline patient characteristics associated with treatment duration in multivariate analyses, overall (cohorts 1 and 2) and according to the reason for treatment initiation (i.e., first-line treatment-naïve patients, and those switching due to intolerance in absence of progression) (cohort 1 only).	From acalabrutinib±venetoclax start to acalabrutinib±venetoclax end, assessed up to 32 months of prospective study follow-up in the cohort 1 and 25 months after the inclusion of the last patient in the cohort 2.
Treatment adherence according to the percentage of days covered (PDC) while receiving acalabrutinib (cohort 1).	Treatment adherence according to the percentage of days covered (PDC) while receiving acalabrutinib, overall and by the reason for treatment initiation (i.e., first-line treatment-naïve patients, and those switching due to intolerance in absence of progression) (cohort 1). The PDC will be based on data available on acalabrutinib treatment in pharmacy records, and defined as the percentage of days a patient has the medication available in a given period of time: PDC (%)=(No.days covered)/(No.days of interest)×100	From acalabrutinib start to acalabrutinib end, assessed up to 32 months of prospective study follow-up (cohort 1).
TTNT (i.e., the time from the date of first dose of acalabrutinib to the first dose of the next treatment for CLL, or death from any cause) (cohorts 1 and 2).	TTNT (i.e., the time from the date of first dose of acalabrutinib to the first dose of the next treatment for CLL, or death from any cause [i.e. deaths are not censored]), overall (cohorts 1 and 2) and according to the reason for treatment initiation (i.e., first-line treatment-naïve patients, and those switching due to intolerance in absence of progression) (cohort 1 only).	From the date of first dose of acalabrutinib to first dose of next CLL treatment or death, assessed up to 32 months of prospective study follow-up in the cohort 1 and 25 months after the inclusion of the last patient in the cohort 2.
OS (i.e., the time from the date of first dose of acalabrutinib to death from any cause) (cohorts 1 and 2).	OS (i.e., the time from the date of first dose of acalabrutinib to death from any cause), overall (cohorts 1 and 2) and according to the reason for treatment initiation (i.e., first-line treatment-naïve patients, and those switching due to intolerance in absence of progression) (cohort 1 only).	From the date of first dose of acalabrutinib to death, assessed up to 32 months of prospective study follow-up in the cohort 1 and 25 months after the inclusion of the last patient in the cohort 2.
Adverse events that lead to acalabrutinib±venetoclax dose changes, temporary interruptions, or permanent discontinuation; that are considered serious during acalabrutinib±venetoclax treatment; and events of clinical interest (cohorts 1 and 2).	Adverse events that lead to acalabrutinib±venetoclax dose changes, temporary interruptions, or permanent discontinuation. Adverse events that are considered serious (including fatal events) during acalabrutinib±venetoclax treatment, globally and treatment related (when available). Events of clinical interest (atrial fibrillation, hypertension, bleeding, infections, ventricular arrhythmias, hepatotoxicity, secondary primary malignancies, cytopenia, and pneumonitis) during acalabrutinib treatment, globally and treatment related (when available). They will be described overall (cohorts 1 and 2) and according to the reason for treatment initiation (i.e., first-line treatment-naïve patients, and those switching due to intolerance in absence of progression) (cohort 1 only).	From acalabrutinib±venetoclax start to acalabrutinib±venetoxlax end, assessed up to 32 months of prospective study follow-up in the cohort 1 and 25 months after the inclusion of the last patient in the cohort 2.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best ORR (i.e., the proportion of patients that achieved complete or partial response) during acalabrutinib treatment.	Best ORR (i.e., the proportion of patients that achieved complete or partial response) during acalabrutinib treatment, overall and according to the reason for treatment initiation (i.e., first-line treatment-naïve patients, and those switching due to intolerance in absence of progression).	From acalabrutinib start to acalabrutinib end, assessed up to 3.5 years of prospective study follow-up.
rwPFS (i.e., the time from the date of first dose of acalabrutinib to disease progression, or death from any cause).	rwPFS (i.e., the time from the date of first dose of acalabrutinib to disease progression, or death from any cause), overall and according to the reason for treatment initiation (i.e., first-line treatment-naïve patients, and those switching due to intolerance in absence of progression).	From the date of first dose of acalabrutinib to disease progression or death from any cause, whichever came first, assessed up to 3.5 years of prospective study follow-up.
Scores on the EORTC QLQ-C30, its specific module for CLL QLQ-CLL17, and SATMED-Q during acalabrutinib treatment.	Scores on the EORTC Core Quality of Life questionnaire (EORTC QLQ-C30) and its specific module for CLL QLQ-CLL17 reported at inclusion, month 3, month 6 and subsequent every 6-month follow-up during acalabrutinib treatment. Satisfaction with acalabrutinib treatment reported at study inclusion, month 3, month 6 and subsequent every 6-month follow-up during acalabrutinib treatment (Treatment Satisfaction Questionnaire; SATMED-Q). These outcomes will be evaluated overall and according to the reason for treatment initiation (i.e., first-line treatment-naïve patients, and those switching due to intolerance in absence of progression).	Study inclusion, month 3, month 6 and subsequent every 6 months during acalabrutinib treatment up to 3.5 years of prospective study follow-up.
Frequency of patients switching from capsules to tablets (if available).	Frequency of patients switching from capsules to tablets (if available).	From acalabrutinib start to acalabrutinib end, assessed up to 3.5 years of prospective study follow-up.
Patient satisfaction after switching from capsules to tablets (if available).	Patient satisfaction according to SATMED-Q scores after switching from capsules to tablets (if available).	From acalabrutinib start to acalabrutinib end, assessed up to 3.5 years of prospective study follow-up.
Patient adherence after switching from capsules to tablets (if available).	Patient adherence according to PDC after switching from capsules to tablets (if available).	From acalabrutinib start to acalabrutinib end, assessed up to 3.5 years of prospective study follow-up.

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): July 11, 2023
• Primary Completion (Estimated): March 31, 2029
• Study Completion (Estimated): March 31, 2029

Study Registration Dates

• First Submitted: June 29, 2023
• First Submitted That Met QC Criteria: August 10, 2023
• First Posted (Actual): August 21, 2023

Study Record Updates

• Last Update Posted (Actual): August 4, 2026
• Last Update Submitted That Met QC Criteria: July 31, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Observational; 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
• Other Study ID Numbers: D8221R00003

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.

"Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.

• 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No