Ignite Creation Date:
2024-10-26 @ 3:37 PM
Last Modification Date:
2024-10-26 @ 3:37 PM
Study NCT ID:
NCT06548152
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-07-17
Brief Title:
AQUALISQoL of CLL Patients Treated With Acalabrutinib in France Retrospective Study Based on Data From PLATON Database
Sponsor:
None
Organization:
None
Study Overview
Official Title:
AQUALIS Quality of Life of Patients With Chronic Lymphocytic Leukemia Treated With Acalabrutinib in France a Retrospective Observational Study Based on Data Extracted From the PLATON Database
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
AQUALIS
Brief Summary:
QoL is often not assessed in real-world studies hence there is limited understanding about the real-world QoL of patients diagnosed with CLL Besides studies evaluating QoL have largely focused on comparing treated and untreated populations In particular QoL of patients treated with acalabrutinib has not been evaluated in a real-life setting
The aim of this study is to describe the QoL of CLL patients treated with acalabrutinib between the treatment initiation and twelve months after in a real-life setting
The aim of this study is to describe the QoL of CLL patients treated with acalabrutinib between the treatment initiation and twelve months after in a real-life setting
Detailed Description:
PROTOCOL SYNOPSIS
BackgroundRationale
CLL is the most prevalent leukemia among adults The estimated incidence of CLL was 4 674 in 2018 in France 59 in men with a median age of 71 in men and 73 in women 95 of patients are older than 51 yrs at diagnosis 5-yr survival is above 89 for patients diagnosed between 2010 and 2015 Yet CLL cannot be cured Some patients will require monitoring while others need to be treated Treatment is based on both chemo-immunotherapies CIT and target therapies Treatment choice depends on several parameters age patient general condition comorbidities prognostic factors cytogenetic status CIT have shown to improve overall survival OS Targeted therapies have changed the management and offer treatment options among older patients and those with comorbidities who have unacceptable side effects with CIT Acalabrutinib also known as ACP-196 and Calquence is a selective and irreversible small molecule inhibitor of BTK Authorized as 1st or 2nd line treatment in France in November 2020 Its safety and efficacy were explored in phase III clinical trials ELEVATE-TN ASCEND and ELEVATE-RR Because CLL is by definition a chronic disease and requires long-term treatment and because many patients have comorbidities it is essential to consider quality of life QoL of patients14 In addition the condition itself substantially impacts QoLPatients with CLL experienced worse QoL than the general population across several domains including symptoms eg fatigue and sleep disturbances as well as physical and mental functioning Acalabrutinib has shown great efficacy associated with a good safety profile in clinical trials111214 Moreover it is an oral treatment that does not require intravenous injections when taken as monotherapy This treatment modality associated with the favorable safety profile of acalabrutinib could have a positive impact on the QoL of patients Indeed patients could continue to live a normal life at home surrounded by their relatives QoL is often not assessed in real-world RW studies hence there is limited understanding about the RW QoL of patients diagnosed with CLL Besides studies evaluating QoL have largely focused on comparing treated and untreated populations In particular QoL of patients treated with acalabrutinib has not been evaluated in a real-life setting The aim of this study is to describe the QoL of CLL patients treated with acalabrutinib between the treatment initiation and 12 months after in a real-life setting
Objectives
Primary Objective To measure QoL score of CLL patients treated with acalabrutinib from treatment initiation and up to 12 months -Overall scores and scores in each domain of QoL questionnaires EORTC-QLQ-C30 at acalabrutinib treatment initiation and at 3 6 9 and 12 months after initiation -Proportion of patients with an increase a decrease or no change in QoL scores over time between each time point Main Secondary Objectives To describe QoL and precisely the level and evolution of all symptoms -Patients demographics age gender at acalabrutinib treatment initiation -Clinical characteristics at acalabrutinib treatment initiation CLL diagnosis Binet classification comorbidities of interest -Clinical characteristics quarterly up to 12 months disease status -Score is calculated with standardized EORTC-CLL17 questionnaire At acalabrutinib treatment initiation and at 3 6 9 and 12 months after initiation To measure the evolution of observance -Score is calculated with standardized GIRERD grid at 3 6 9 and 12 months after initiation To describe treatment patterns in CLL patients treated with acalabrutinib overall and by age group -Acalabrutinib treatment line monotherapy or with obinutuzumab posology duration reason for discontinuation if any To describe participating sites characteristics -Type of physician practice publicprivatemixed -Type of care structure CHU CHG -Existing patient support program yesno type Methods Study design This is a retrospective observational study focusing on the QoL and experience of CLL patients treated with acalabrutinib in France in a real-life setting This study is using secondary data of patients included in the national multicenter longitudinal cohort PLATON sponsor HOSPITALIDEE clinical trial registration N 2023-A01569-36 This cohort is enrolling patients with hematological malignancies including CLL patients A follow-up of 12 months from initial cancer diagnosis or patient enrollment is planned in the PLATON study The current AQUALIS study mainly aims at describing CLL patient QoL and experience from acalabrutinib initiation quarterly and up to 12 months post initiation Patient and disease characteristics treatment patterns disease status over time will also be described Thus the patient population eligible for entering the AQUALIS study will be treatment naïve CLL patients enrolled in the PLATON study and having initiated acalabrutinib at the time of data extraction Only patients with a full T0 will be considered as included Several data extraction from PLATON database and data cut-off are planned to address AQUALIS study objectives and planned publication plan No extra-visit nor specific additional examination nor intervention are required for patients eligible to enter the AQUALIS study Data to be extracted and analyzed will be exclusively those already recorded in the PLATON database HOSPITALIDEE will insure that in each center participating to PLATON cohort all patients fulfilling the PLATON eligibility criteria have been informed about the PLATON study before being enrolled in the PLATON database and do not object to secondary use of their data The AQUALIS study does not involve human person according to the French legislation Data Sources The AQUALIS study will be a secondary use of data issued from the French PLATON cohort The PLATON cohort is a national prospective cohort enrolling patients diagnosed with malignant hemopathies aiming at to offer personalized information to patients to improve their QoL and guide their use of complementary care PLATON is designed to ensure patients follow-up in the long term and on a European scale This project is sponsored by HOSPITALIDEE and coordinated by Loic Raynal under the scientific responsibility of Pr Loïc Ysebaert The sponsor has been granted with appropriate regulatory and ethics local approvals for the conduct of the study Patients eligible to PLATON are informed about the study and are requested to sign a specific informed consent if they do agree for participation and for their data being processed It is planned that 120 patients are enrolled and followed-up to 12 months from enrollment Data are collected at patient inclusion and on a regular basis every 3 months during the follow-up according to routine practice Socio-demographic clinical biological data treatments patterns etcPathology treatments history lifestyle sociodemographic analysis patient profile preferences are collected via an electronic data capture tool and hosted in a centralized securized data center Patient QoL and experience is also collected at 5 timepoints using 4 questionnaires The PLATON database is managed by HOSPITALIDEE using their own software A data-management plan and a consistency check program were established during database development Quality controls of the data are performed i automatic data consistency check ii data management control through regular sending of queries iii regular e-control of entered data by the project manager iv remote and or on-site data monitoring of at least 100 of the data entered Data collection and hosting data management and statistical analysis of PLATON data are handled by HOSPITALIDEE No patient-level data will be transmitted to AstraZeneca Only aggregated data will be delivered based on the current AQUALIS protocol and a related statistical analysis plan Study population The AQUALIS study population will be a subgroup of patients enrolled in PLATON database following inclusion and exclusion criteria as described below
Inclusion-Exclusion criteria please see details in ELIGIBILITY SECTION Outcomes Please see details OUTCOME MEASURES SECTION
Patient study questionnaires
In our research protocol we have chosen the EORTC QLQ-C30 as our primary tool for evaluating quality of life To address the potential overlap with the MD Anderson Symptom Inventory MDASI we have substituted the MDASI with the QLQ-CLL17 a supplementary module to the QLQ-C30 specifically designed for chronic lymphocytic leukemia This addition enhances the relevance and specificity of our studys context Alongside the QLQ-C30 the QLQ-CLL17 provides a comprehensive assessment tailored to our research objectives Furthermore we have opted to use neither FACIT-TS-G questionnaire nor the Cancer Therapy Satisfaction Questionnaire CTSQ Our decision was influenced by concerns about redundancy and the length of these questionnaires which could potentially burden respondents and affect the quality of the data collected This decision was also rooted in the observation that the measurement of satisfaction is conducted in a notably heterogeneous manner across existing questionnaires lacking a standard and only partially covering the scope of satisfaction This perspective was shared by several hematologists we collaborate with including Loïc Ysebaert who notes that to date no satisfaction questionnaire has become the reference
While its possible to publish using any questionnaire the main goal of our protocol and studies conducted through Platon is to utilize standardized instruments like the QLQ-C30 allowing for the comparison of results However satisfaction with treatment serves as an illuminating indicator rather than a comparative outcome to judge the superiority of patients quality of life It is more of an insight This view is endorsed by the Aqualis scientific committee with whom we co-developed the satisfaction questionnaire Based on patient feedback and scientific committee recommendations we have created a simplified non-standardized version to more effectively capture treatment satisfaction prioritizing the relevance and comfort of our participants in the data collection process
The aim is to ensure the highest possible completion rate over time from T0 to T12 The questionnaire we have implemented is inspired by the CTSQ featuring questions on the patients overall satisfaction the impact of their treatment on daily life the occurrence of adverse effects and their impact with a disclaimer directing to the adverse effect reporting portal and the potential use of support care services
Additionally the Girerd questionnaire will help monitoring treatment adherence providing valuable insights into how patients comply with their prescribed regimens
Sample Size Estimations - Given the observational nature of the study and the descriptive nature of the primary objective no pre-defined hypothesis testing is expected to be used to address the primary objective - Assuming a 20 loss of follow-up the number of patients to address the exploratory objective will be 1200896 Statistical Analysis With a sample size of 120 patients treated with acalabrutinib as a first-line therapy we will have enough power to detect a change including an improvement in the QoL of patients over time with one QoL EORTC-QLQ-C30 A comprehensive statistical analysis plan SAP will be developed before the first analysis and finalized before the database lock A descriptive analysis will be conducted on all variables for which data have been extracted for the overall study population and sub-groups of interest Continuous quantitative variable summaries will include the number of patients N with non-missing values mean standard deviation SD median minimum maximum 1st and 3rd quartiles Categorical qualitative variables summaries will include the frequency and percentage of patients per category The denominator for percentage calculations will be based on the number of observed data unless otherwise specified All applicable statistical tests will be two-sided and will be performed at a 5 significance level Missing values will not be imputed Results will be presented overall and by treatment line and by age group as specified in the study objectives Additional subgroups of interest may be further investigated and discussed in the protocol andor the SAP
BackgroundRationale
CLL is the most prevalent leukemia among adults The estimated incidence of CLL was 4 674 in 2018 in France 59 in men with a median age of 71 in men and 73 in women 95 of patients are older than 51 yrs at diagnosis 5-yr survival is above 89 for patients diagnosed between 2010 and 2015 Yet CLL cannot be cured Some patients will require monitoring while others need to be treated Treatment is based on both chemo-immunotherapies CIT and target therapies Treatment choice depends on several parameters age patient general condition comorbidities prognostic factors cytogenetic status CIT have shown to improve overall survival OS Targeted therapies have changed the management and offer treatment options among older patients and those with comorbidities who have unacceptable side effects with CIT Acalabrutinib also known as ACP-196 and Calquence is a selective and irreversible small molecule inhibitor of BTK Authorized as 1st or 2nd line treatment in France in November 2020 Its safety and efficacy were explored in phase III clinical trials ELEVATE-TN ASCEND and ELEVATE-RR Because CLL is by definition a chronic disease and requires long-term treatment and because many patients have comorbidities it is essential to consider quality of life QoL of patients14 In addition the condition itself substantially impacts QoLPatients with CLL experienced worse QoL than the general population across several domains including symptoms eg fatigue and sleep disturbances as well as physical and mental functioning Acalabrutinib has shown great efficacy associated with a good safety profile in clinical trials111214 Moreover it is an oral treatment that does not require intravenous injections when taken as monotherapy This treatment modality associated with the favorable safety profile of acalabrutinib could have a positive impact on the QoL of patients Indeed patients could continue to live a normal life at home surrounded by their relatives QoL is often not assessed in real-world RW studies hence there is limited understanding about the RW QoL of patients diagnosed with CLL Besides studies evaluating QoL have largely focused on comparing treated and untreated populations In particular QoL of patients treated with acalabrutinib has not been evaluated in a real-life setting The aim of this study is to describe the QoL of CLL patients treated with acalabrutinib between the treatment initiation and 12 months after in a real-life setting
Objectives
Primary Objective To measure QoL score of CLL patients treated with acalabrutinib from treatment initiation and up to 12 months -Overall scores and scores in each domain of QoL questionnaires EORTC-QLQ-C30 at acalabrutinib treatment initiation and at 3 6 9 and 12 months after initiation -Proportion of patients with an increase a decrease or no change in QoL scores over time between each time point Main Secondary Objectives To describe QoL and precisely the level and evolution of all symptoms -Patients demographics age gender at acalabrutinib treatment initiation -Clinical characteristics at acalabrutinib treatment initiation CLL diagnosis Binet classification comorbidities of interest -Clinical characteristics quarterly up to 12 months disease status -Score is calculated with standardized EORTC-CLL17 questionnaire At acalabrutinib treatment initiation and at 3 6 9 and 12 months after initiation To measure the evolution of observance -Score is calculated with standardized GIRERD grid at 3 6 9 and 12 months after initiation To describe treatment patterns in CLL patients treated with acalabrutinib overall and by age group -Acalabrutinib treatment line monotherapy or with obinutuzumab posology duration reason for discontinuation if any To describe participating sites characteristics -Type of physician practice publicprivatemixed -Type of care structure CHU CHG -Existing patient support program yesno type Methods Study design This is a retrospective observational study focusing on the QoL and experience of CLL patients treated with acalabrutinib in France in a real-life setting This study is using secondary data of patients included in the national multicenter longitudinal cohort PLATON sponsor HOSPITALIDEE clinical trial registration N 2023-A01569-36 This cohort is enrolling patients with hematological malignancies including CLL patients A follow-up of 12 months from initial cancer diagnosis or patient enrollment is planned in the PLATON study The current AQUALIS study mainly aims at describing CLL patient QoL and experience from acalabrutinib initiation quarterly and up to 12 months post initiation Patient and disease characteristics treatment patterns disease status over time will also be described Thus the patient population eligible for entering the AQUALIS study will be treatment naïve CLL patients enrolled in the PLATON study and having initiated acalabrutinib at the time of data extraction Only patients with a full T0 will be considered as included Several data extraction from PLATON database and data cut-off are planned to address AQUALIS study objectives and planned publication plan No extra-visit nor specific additional examination nor intervention are required for patients eligible to enter the AQUALIS study Data to be extracted and analyzed will be exclusively those already recorded in the PLATON database HOSPITALIDEE will insure that in each center participating to PLATON cohort all patients fulfilling the PLATON eligibility criteria have been informed about the PLATON study before being enrolled in the PLATON database and do not object to secondary use of their data The AQUALIS study does not involve human person according to the French legislation Data Sources The AQUALIS study will be a secondary use of data issued from the French PLATON cohort The PLATON cohort is a national prospective cohort enrolling patients diagnosed with malignant hemopathies aiming at to offer personalized information to patients to improve their QoL and guide their use of complementary care PLATON is designed to ensure patients follow-up in the long term and on a European scale This project is sponsored by HOSPITALIDEE and coordinated by Loic Raynal under the scientific responsibility of Pr Loïc Ysebaert The sponsor has been granted with appropriate regulatory and ethics local approvals for the conduct of the study Patients eligible to PLATON are informed about the study and are requested to sign a specific informed consent if they do agree for participation and for their data being processed It is planned that 120 patients are enrolled and followed-up to 12 months from enrollment Data are collected at patient inclusion and on a regular basis every 3 months during the follow-up according to routine practice Socio-demographic clinical biological data treatments patterns etcPathology treatments history lifestyle sociodemographic analysis patient profile preferences are collected via an electronic data capture tool and hosted in a centralized securized data center Patient QoL and experience is also collected at 5 timepoints using 4 questionnaires The PLATON database is managed by HOSPITALIDEE using their own software A data-management plan and a consistency check program were established during database development Quality controls of the data are performed i automatic data consistency check ii data management control through regular sending of queries iii regular e-control of entered data by the project manager iv remote and or on-site data monitoring of at least 100 of the data entered Data collection and hosting data management and statistical analysis of PLATON data are handled by HOSPITALIDEE No patient-level data will be transmitted to AstraZeneca Only aggregated data will be delivered based on the current AQUALIS protocol and a related statistical analysis plan Study population The AQUALIS study population will be a subgroup of patients enrolled in PLATON database following inclusion and exclusion criteria as described below
Inclusion-Exclusion criteria please see details in ELIGIBILITY SECTION Outcomes Please see details OUTCOME MEASURES SECTION
Patient study questionnaires
In our research protocol we have chosen the EORTC QLQ-C30 as our primary tool for evaluating quality of life To address the potential overlap with the MD Anderson Symptom Inventory MDASI we have substituted the MDASI with the QLQ-CLL17 a supplementary module to the QLQ-C30 specifically designed for chronic lymphocytic leukemia This addition enhances the relevance and specificity of our studys context Alongside the QLQ-C30 the QLQ-CLL17 provides a comprehensive assessment tailored to our research objectives Furthermore we have opted to use neither FACIT-TS-G questionnaire nor the Cancer Therapy Satisfaction Questionnaire CTSQ Our decision was influenced by concerns about redundancy and the length of these questionnaires which could potentially burden respondents and affect the quality of the data collected This decision was also rooted in the observation that the measurement of satisfaction is conducted in a notably heterogeneous manner across existing questionnaires lacking a standard and only partially covering the scope of satisfaction This perspective was shared by several hematologists we collaborate with including Loïc Ysebaert who notes that to date no satisfaction questionnaire has become the reference
While its possible to publish using any questionnaire the main goal of our protocol and studies conducted through Platon is to utilize standardized instruments like the QLQ-C30 allowing for the comparison of results However satisfaction with treatment serves as an illuminating indicator rather than a comparative outcome to judge the superiority of patients quality of life It is more of an insight This view is endorsed by the Aqualis scientific committee with whom we co-developed the satisfaction questionnaire Based on patient feedback and scientific committee recommendations we have created a simplified non-standardized version to more effectively capture treatment satisfaction prioritizing the relevance and comfort of our participants in the data collection process
The aim is to ensure the highest possible completion rate over time from T0 to T12 The questionnaire we have implemented is inspired by the CTSQ featuring questions on the patients overall satisfaction the impact of their treatment on daily life the occurrence of adverse effects and their impact with a disclaimer directing to the adverse effect reporting portal and the potential use of support care services
Additionally the Girerd questionnaire will help monitoring treatment adherence providing valuable insights into how patients comply with their prescribed regimens
Sample Size Estimations - Given the observational nature of the study and the descriptive nature of the primary objective no pre-defined hypothesis testing is expected to be used to address the primary objective - Assuming a 20 loss of follow-up the number of patients to address the exploratory objective will be 1200896 Statistical Analysis With a sample size of 120 patients treated with acalabrutinib as a first-line therapy we will have enough power to detect a change including an improvement in the QoL of patients over time with one QoL EORTC-QLQ-C30 A comprehensive statistical analysis plan SAP will be developed before the first analysis and finalized before the database lock A descriptive analysis will be conducted on all variables for which data have been extracted for the overall study population and sub-groups of interest Continuous quantitative variable summaries will include the number of patients N with non-missing values mean standard deviation SD median minimum maximum 1st and 3rd quartiles Categorical qualitative variables summaries will include the frequency and percentage of patients per category The denominator for percentage calculations will be based on the number of observed data unless otherwise specified All applicable statistical tests will be two-sided and will be performed at a 5 significance level Missing values will not be imputed Results will be presented overall and by treatment line and by age group as specified in the study objectives Additional subgroups of interest may be further investigated and discussed in the protocol andor the SAP
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None