Clinical trial NCT05517265: Acalabrutinib in Patients With Chronic Lymphocytic Leukemia With Direct Oral Anticoagulation (CICERO)
Official title: A Non-interventional, Prospective, Open-label, Observational Study Evaluating the Effectiveness and Safety of Acalabrutinib (Calquence®) in Patients With Chronic Lymphocytic Leukemia (CLL) Receiving Direct Oral Anticoagulation (DOAC).
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: CLL
Keywords: CLL
Acalabrutinib (+/- Obinutuzumab)
DOAC
Lead sponsor: iOMEDICO AG
Sponsor class: INDUSTRY
Collaborators: name: AstraZeneca
First posted: 2022-08-26
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult patients with CLL receiving acalabrutinib (+/- obinutuzumab) and co-medication with DOAC.

Brief summary: The goal of CICERO is to investigate the clinical outcome with a particular focus on prospective data on safety using acalabrutinib (+/- obinutuzumab) in CLL patients receiving co-medication with DOACs (edoxaban, rivaroxaban, dabigatran, apixaban) irrespective of treatment line.

Detailed description: The non-interventional study (NIS) CICERO will collect real-world data to explore acalabrutinib (+/- obinutuzumab) in adult CLL patients (irrespective of treatment line) who receive co-medication with DOACs. The primary focus of the study is to investigate the incidence proportion of bleeding events. Due to the mostly elderly CLL patient population, CLL patients often suffer from multiple cardiovascular comorbidities including atrial fibrillation (AF), deep vein thrombosis (DVT) or pulmonary embolism (PE) which make anticoagulation mandatory.

Up to now, no systematic and prospective evaluation on interactions of BTKis and DOACs has been conducted.

In Order to assess bleeding events, a questionnaire will be used to document if bleeding events occurred in-between visits in routine care. Patients will be asked at each visit if distinct events occurred in the time between the last visit until the current visit and discuss the questionnaire with the physician to determine of any (S)AE occurred until end of acalabrutinib treatment.

Eligibility criteria: Inclusion Criteria:

* 18 years of age or older
* Patients with chronic lymphocytic leukemia (CLL) and decision for treatment with acalabrutinib (+/- obinutuzumab) according to current SmPC as assessed by the treating physician or already started treatment with acalabrutinib (+/- obinutuzumab) according to current SmPC no longer than 6 weeks ago
* Other concomitant disease resulting in medical need of or already under treatment with direct oral anticoagulant (DOAC) treatment with edoxaban (Lixiana®) or rivaroxaban (Xarelto®) or dabigatran (Pradaxa®) or apixaban (Eliquis®) according to the respective current SmPC.
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* Signed, written informed consent.

Exclusion Criteria:

* Combination of acalabrutinib with other substances than obinutuzumab for CLL treatment
* Participation in an interventional clinical trial with acalabrutinib

Primary outcomes:
measure: Incidence proportion of patients with major bleeding event according to Schulman et al.
timeFrame: Baseline until end of acalabrutinib treatment (+ 30 days safety follow-up); up to 41 months
Secondary outcomes:
measure: Incidence proportion of clinically relevant non-major (CRNM) bleeding events
timeFrame: Baseline, up to 41 months
measure: Major (according to Schulman et al.) and/or CRNM bleeding events.
timeFrame: Baseline, up to 41 months
measure: Any bleeding event.
timeFrame: Baseline, up to 41 months
measure: Incidence proportion of major bleeding according to Ghia et al.
timeFrame: Baseline, up to 41 months
measure: Time to first Occurrence of major bleeding events
timeFrame: Baseline, up to 41 months
measure: Incidence proportion of central nervous system (CNS) bleeding events
timeFrame: Baseline, up to 41 months
measure: Patient safety regarding mortality
timeFrame: Baseline, up to 41 months
measure: Patient safety in terms of interactions with effectiveness of DOAC
timeFrame: Baseline, up to 41 months
measure: VTE (venous thromboembolism)-related death
timeFrame: Baseline, up to 41 months
measure: Overall response rate (ORR)
timeFrame: Baseline, up to 41 months
measure: Progression-free survival (PFS)
timeFrame: Baseline, up to 41 months
measure: Overall survival (OS)
timeFrame: Baseline, up to 41 months
measure: Therapy decision making
timeFrame: Baseline
measure: Previous therapies
timeFrame: Baseline
measure: Acalabrutinib (+/- obinutuzumab) treatment: Duration
timeFrame: Baseline, up to 41 months
measure: Acalabrutinib (+/- obinutuzumab) treatment: Dose intensity
timeFrame: Baseline, up to 41 months
measure: Obinutuzumab treatment: Duration
timeFrame: Baseline, up to 41 months
measure: Reasons for end of treatment of obinutuzumab
timeFrame: Baseline, up to 41 months
measure: Types of DOAC
timeFrame: Baseline, up to 41 months
measure: Reasons for DOAC treatment
timeFrame: Baseline, up to 41 months
measure: DOAC treatment: Duration
timeFrame: Baseline, up to 41 months
measure: DOAC treatment: Dose modifications
timeFrame: Baseline, up to 41 months
measure: DOAC treatment: Reasons for dose modifications
timeFrame: Baseline, up to 41 months
measure: DOAC treatment: Reasons for end of treatment
timeFrame: Baseline, up to 41 months
measure: Time from onset to DOAC to start of acalabrutinib
timeFrame: Baseline, up to 41 months
measure: Concomitant medication
timeFrame: Baseline, up to 41 months
Other outcomes:
Locations:
city: Saalfeld
country: Germany
facility: Prof. Dr. Fenchel & Dr. Winkler MVZ Träger GbR
state: Thüringen
Study officials:
affiliation: Onkologische Praxisklinik Hämatologie/ Onkologie und Gerinnungsstörungen
name: Klaus Fenchel, Prof. Dr.
role: STUDY_CHAIR
References:
citation: Schulman S, Kearon C; Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005 Apr;3(4):692-4. doi: 10.1111/j.1538-7836.2005.01204.x.
citation: Ghia P, Pluta A, Wach M, Lysak D, Kozak T, Simkovic M, Kaplan P, Kraychok I, Illes A, de la Serna J, Dolan S, Campbell P, Musuraca G, Jacob A, Avery E, Lee JH, Liang W, Patel P, Quah C, Jurczak W. ASCEND: Phase III, Randomized Trial of Acalabrutinib Versus Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia. J Clin Oncol. 2020 Sep 1;38(25):2849-2861. doi: 10.1200/JCO.19.03355. Epub 2020 May 27.