Observational Study of Acalabrutinib in Patients With Chronic Lymphocytic Leukaemia in the United Kingdom

Study Overview
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Brief Summary
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This is a retrospective observational research study to describe the characteristics and real-world clinical outcomes of patients with chronic lymphocytic leukaemia receiving acalabrutinib in the United Kingdom (the EPIC study). Physicians treating chronic lymphocytic leukaemia patients with acalabrutinib, where the patients started treatment as part of the acalabrutinib Early Access Programme (EAP), will be invited to recruit patients. Clinical data will be extracted from the patients' clinical records in line with local laws. Data from this study will provide UK-specific real-world data on patients who were started on acalabrutinib as part of the UK acalabrutinib EAP.

Detailed Description
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Primary Objectives: a. To estimate real-world progression-free survival in patients with CLL who received acalabrutinib in the first-line. Secondary Objectives: To estimate real-world overall survival in patients with CLL who received acalabrutinib in the first-line. To describe real-world response rate to acalabrutinib in patients with CLL who received acalabrutinib in the first-line. To describe the healthcare resource utilisation in patients with CLL who received acalabrutinib in the first-line. To describe post-progression treatment patterns in patients with CLL who progressed from first-line acalabrutinib. To describe real-world clinical progression free survival in patients with CLL who received acalabrutinib in the first-line and progressed during acalabrutinib treatment. To describe acalabrutinib treatment patterns in patients with CLL who received acalabrutinib in the first-line. To describe baseline clinical and demographic characteristics in patients with CLL who received acalabrutinib in the first-line.

Official Title
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A Non-interventional, Observational Cohort Study of Chronic Lymphocytic Leukaemia Patients Treated With Acalabrutinib in the First-line Setting Through the UK Early Access Programme: Early Access Programme Outcomes In aCalabrutinib (EPIC).

Conditions
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Chronic Lymphocytic Leukemia, CLL

Intervention / Treatment
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* Drug: Acalabrutinib


Participation Criteria
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Eligibility Criteria
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The study population will include treatment-naïve patients with chronic lymphocytic lymphoma (CLL)* who meet the following inclusion criteria: Treatment-naïve CLL patients who were initiated on acalabrutinib as part of the UK Early Access Programme Received their first dose of acalabrutinib between 1 April 2020 and 1 April 2021 Patients aged ≥18 years old Note: patients later found to have small lymphocytic lymphoma (SLL) may also be included in the EAP. Exclusion Criteria: - None listed in study protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 130 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group 1<br>Patients with chronic lymphocytic leukaemia treated with acalabrutinib in first line | Drug: Acalabrutinib<br>* Acalabrutinib<br>* Other names: Calquence;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Real-world progression free survival (rwPFS) | rwPFS will be defined as the time from index date until earliest record of real-world progression event as determined by physicians' assessment, or death (if no progression) or end of follow-up (for censored observations) whilst on first line treatment. | 12 months | 
| Real-world progression free survival (rwPFS) | rwPFS will be defined as the time from index date until earliest record of real-world progression event as determined by physicians' assessment, or death (if no progression) or end of follow-up (for censored observations) whilst on first line treatment. | 24 months | 
| Real-world progression free survival (rwPFS) | rwPFS will be defined as the time from index date until earliest record of real-world progression event as determined by physicians' assessment, or death (if no progression) or end of follow-up (for censored observations) whilst on first line treatment. | 36 months | 
| Real-world progression free survival (rwPFS) | rwPFS will be defined as the time from index date until earliest record of real-world progression event as determined by physicians' assessment, or death (if no progression) or end of follow-up (for censored observations) whilst on first line treatment. | 48 months | 
| Real-world progression free survival (rwPFS) | rwPFS will be defined as the time from index date until earliest record of real-world progression event as determined by physicians' assessment, or death (if no progression) or end of follow-up (for censored observations) whilst on first line treatment. | 60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Real-world overall survival (rwOS) | rwOS will be defined as the time from index date up to death or last date the patient was known to be alive (for censored observations). | 12 months | 
| Real-world overall survival (rwOS) | rwOS will be defined as the time from index date up to death or last date the patient was known to be alive (for censored observations). | 24 months | 
| Real-world overall survival (rwOS) | rwOS will be defined as the time from index date up to death or last date the patient was known to be alive (for censored observations). | 36 months | 
| Real-world overall survival (rwOS) | rwOS will be defined as the time from index date up to death or last date the patient was known to be alive (for censored observations). | 48 months | 
| Real-world overall survival (rwOS) | rwOS will be defined as the time from index date up to death or last date the patient was known to be alive (for censored observations). | 60 months | 
| Real-world response rate (rwRR) | rwRR will be defined as the proportion of patients with a recorded significant anti-cancer response and will be defined here as the sum of complete response, partial response and partial response + lymphocytosis. Response will be based on the on the documented assessment of the local investigator. | 12 months | 
| Real-world response rate (rwRR) | rwRR will be defined as the proportion of patients with a recorded significant anti-cancer response and will be defined here as the sum of complete response, partial response and partial response + lymphocytosis. Response will be based on the on the documented assessment of the local investigator. | 24 months | 
| Real-world response rate (rwRR) | rwRR will be defined as the proportion of patients with a recorded significant anti-cancer response and will be defined here as the sum of complete response, partial response and partial response + lymphocytosis. Response will be based on the on the documented assessment of the local investigator. | 36 months | 
| Real-world response rate (rwRR) | rwRR will be defined as the proportion of patients with a recorded significant anti-cancer response and will be defined here as the sum of complete response, partial response and partial response + lymphocytosis. Response will be based on the on the documented assessment of the local investigator. | 48 months | 
| Real-world response rate (rwRR) | rwRR will be defined as the proportion of patients with a recorded significant anti-cancer response and will be defined here as the sum of complete response, partial response and partial response + lymphocytosis. Response will be based on the on the documented assessment of the local investigator. | 60 months | 
| Real-world clinical progression free survival 2 (rwPFS2) | rwPFS2 will be defined as the time from index date to the date of the second record of real-world progression (as determined by physicians' assessment) or death due to any cause (if no progression), whichever occurs first whilst on second line treatment. If there is no second progression or the patient is lost to follow-up, PFS2 will be censored at the time of the last available tumour assessment. | 12 months | 
| Real-world clinical progression free survival 2 (rwPFS2) | rwPFS2 will be defined as the time from index date to the date of the second record of real-world progression (as determined by physicians' assessment) or death due to any cause (if no progression), whichever occurs first whilst on second line treatment. If there is no second progression or the patient is lost to follow-up, PFS2 will be censored at the time of the last available tumour assessment. | 24 months | 
| Real-world clinical progression free survival 2 (rwPFS2) | rwPFS2 will be defined as the time from index date to the date of the second record of real-world progression (as determined by physicians' assessment) or death due to any cause (if no progression), whichever occurs first whilst on second line treatment. If there is no second progression or the patient is lost to follow-up, PFS2 will be censored at the time of the last available tumour assessment. | 36 months | 
| Real-world clinical progression free survival 2 (rwPFS2) | rwPFS2 will be defined as the time from index date to the date of the second record of real-world progression (as determined by physicians' assessment) or death due to any cause (if no progression), whichever occurs first whilst on second line treatment. If there is no second progression or the patient is lost to follow-up, PFS2 will be censored at the time of the last available tumour assessment. | 48 months | 
| Real-world clinical progression free survival 2 (rwPFS2) | rwPFS2 will be defined as the time from index date to the date of the second record of real-world progression (as determined by physicians' assessment) or death due to any cause (if no progression), whichever occurs first whilst on second line treatment. If there is no second progression or the patient is lost to follow-up, PFS2 will be censored at the time of the last available tumour assessment. | 60 months | 
| Frequency of acalabrutinib dose interruptions | A treatment interruption will be defined as clinician or patient-initiated temporary treatment cessation of acalabrutinib, where treatment is known to have been recommenced at any time within the observation window (without initiation on a different systemic treatment for CLL in the intervening period). | Through study completion, an average of 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CLL, real-world evidence, acalabrutinib