Chronic Lymphocytic Leukemia
Conditions
Keywords
Observational, Chronic lymphocytic leukemia, Acalabrutinib
Brief summary
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).
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.
Interventions
None listed
Sponsors
AstraZeneca
Study design
Observational model
COHORT
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients on acalabrutinib therapy at 24 months after treatment initiation (cohort 1). | 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: 1. the reason for treatment initiation (i.e., first-line treatment-naïve patients, and those switching due to intolerance in absence of progression), 2. presence/absence of risk factors (i.e., del17p, TP53 mutation, and unmutated IGHV). 3. cardiovascular comorbidities (yes/no). |
| Real-world overall response rate (rwORR) achieved until the end of the observational period for first-line fixed duration acalabrutinib therapy (cohort 2) | 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. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Acalabrutinib±venetoclax doses (cohorts 1 and 2). | 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. | 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. |
| Patients with acalabrutinib±venetoclax dose adjustments (n, %), temporary interruptions (n, %), and permanent discontinuations (n, %) (cohorts 1 and 2). | 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. | 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. |
| Treatment duration in months (cohorts 1 and 2). | 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 (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). |
| Treatment adherence according to the percentage of days covered (PDC) while receiving acalabrutinib (cohort 1). | From acalabrutinib start to acalabrutinib end, assessed up to 32 months of prospective study follow-up (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 |
| 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). | 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. | 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). |
| OS (i.e., the time from the date of first dose of acalabrutinib to death from any cause) (cohorts 1 and 2). | 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. | 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). |
| 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). | 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. | 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). |
Countries
Spain
Outcome results
None listed