Acalabrutinib Real World Italian obSErvational Study -ARISE

Chronic Lymphocytic Leukemia Clinical Trial

— ARISE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06205498
• Other study ID #: D8221R00002
• Status: Recruiting
• Start date: August 8, 2023
• Est. completion date: February 28, 2030

Study information

• Verified date: May 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 190
• Est. completion date: February 28, 2030
• Est. primary completion date: February 28, 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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:

1. Age = 18 years old at the date of consent subscription.

2. Diagnosis of CLL.

3. Treatment of CLL with acalabrutinib at physician's discretion initiated between 1st May 2021 and 30th April 2022.

4. 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:

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

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

Drug:
• acalabrutinib
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

Locations

Country	Name	City	State
Italy	Research Site	Alessandria
Italy	Research Site	Ancona
Italy	Research Site	Bari
Italy	Research Site	Barletta
Italy	Research Site	Brescia
Italy	Research Site	Brindisi
Italy	Research Site	Cagliari
Italy	Research Site	Campobasso
Italy	Research Site	Campobasso
Italy	Research Site	Catania
Italy	Research Site	Catanzaro
Italy	Research Site	Cosenza
Italy	Research Site	Crema (Cremona)
Italy	Research Site	Cuneo
Italy	Research Site	Foggia
Italy	Research Site	Frosinone
Italy	Research Site	Genova
Italy	Research Site	Lecce
Italy	Research Site	Messina
Italy	Research Site	Milano
Italy	Research Site	Milano
Italy	Research Site	Monza
Italy	Research Site	Napoli
Italy	Research Site	Padova
Italy	Research Site	Pagani (Salerno)
Italy	Research Site	Perugia
Italy	Research Site	Pescara
Italy	Research Site	Ravenna
Italy	Research Site	Reggio Calabria
Italy	Research Site	Roma
Italy	Research Site	Roma
Italy	Research Site	Roma
Italy	Research Site	Roma
Italy	Research Site	Roma
Italy	Research Site	Rozzano (MI)
Italy	Research Site	Salerno
Italy	Research Site	San Giovanni Rotondo(FG)
Italy	Research Site	Torino
Italy	Research Site	Torino
Italy	Research Site	Torino
Italy	Research Site	Torino
Italy	Research Site	Tricase(LE)
Italy	Research Site	Varese
Italy	Research Site	Viterbo

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Yghea

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	measure effectiveness of acalabrutinib	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)	through study completion, an average of 5 years
Other	evaluate effectiveness of CLL treatments following acalabrutinib discontinuation	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)	through study completion, an average of 5 years
Other	estimate Healthcare Resources Utilization	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.	through study completion, an average of 5 years
Primary	time to acalabrutinib discontinuation	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.	through study completion, an average of 5 years
Secondary	demographic and clinical characteristics of CLL patients treated with acalabrutinib	To describe demographic and clinical characteristics of CLL patients treated with acalabrutinib, by treatment line and potential associations with acalabrutinib permanent discontinuation.	baseline
Secondary	describe acalabrutinib treatment patterns	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	through study completion, an average of 5 years
Secondary	CLL clinical stage	according to Binet staging system (stage A, B, C) according to Eichhorst et al., 2020.	baseline
Secondary	FISH profile	del(11q) del(17p); trisomy 12; del(13q); normal	baseline
Secondary	Date of birth	month/year	baseline
Secondary	gender	male or famale	baseline
Secondary	Height	cm	baseline
Secondary	Weight	Kg	throught study completion, an average of 5 years
Secondary	Body Mass Index	kg/m2	Through study completion, an average of 5 years
Secondary	Medical illness burden	CIRS-G scale	Through study completion, an average of 5 years
Secondary	Red blood cell count	x10^12/L	Through study completion, an average of 5 years
Secondary	White blood cell count	x10^9/L	Through study completion, an average of 5 years
Secondary	platelets count	x10^9/L	Through study completion, an average of 5 years
Secondary	hemoglobin	gr/dL	Through study completion, an average of 5 years
Secondary	differential count of lymphocytes and neutrophils		Through study completion, an average of 5 years
Secondary	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), ß2-microglobulin (mg/dL), IgG, IgA, IgM levels (mg/dL)		baseline
Secondary	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		baseline