Acalabrutinib in Patients With Chronic Lymphocytic Leukemia With Direct Oral Anticoagulation (CICERO)
- Registration Number
- NCT05517265
- Lead Sponsor
- iOMEDICO AG
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 45
- 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.
- Combination of acalabrutinib with other substances than obinutuzumab for CLL treatment
- Participation in an interventional clinical trial with acalabrutinib
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description first-line therapy Calquence Patients enrolled for first-line acalabrutinib (+/- obinutuzumab). later-line therapy Calquence Pre-treated patients enrolled for later-line acalabrutinib therapy.
- Primary Outcome Measures
Name Time Method Incidence proportion of patients with major bleeding event according to Schulman et al. Baseline until end of acalabrutinib treatment (+ 30 days safety follow-up); up to 41 months Bleeding event is defined as major according to Schulmann et al., if it is fatal (contributes to death) and/or symptomatic in a critical area or organ (such as intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome) and/or causing a decrease in hemoglobin of 2 g/dL (1.24 mmol/l) or more or requires a transfusion of 2 or more units of whole blood or red blood cells.
Incidence proportion (cumulative incidence) is calculated as the number of patients with bleeding event while on treatment (+30 days safety follow-up), divided by the number of patients in the full analysis population.
- Secondary Outcome Measures
Name Time Method Patient safety in terms of interactions with effectiveness of DOAC Baseline, up to 41 months Rate of any new or recurrent ischemic stroke or arterial systemic embolism or venous thromboembolic events.
Incidence proportion of major bleeding according to Ghia et al. Baseline, up to 41 months Major bleeding according to Ghia et al. is defined as any serious OR grade ≥3 hemorrhage OR central nervous system (CNS) hemorrhage of any grade, excluding immune thrombocytopenic purpura.
Time to first Occurrence of major bleeding events Baseline, up to 41 months Time to first occurrence of major (according to Schulman et al.) bleeding events.
Incidence proportion of central nervous system (CNS) bleeding events Baseline, up to 41 months Frequencies of patients with CNS bleeding events.
Patient safety regarding mortality Baseline, up to 41 months Mortality from all causes during acalabrutinib therapy.
VTE (venous thromboembolism)-related death Baseline, up to 41 months Incidence proportion of VTE-related death.
Incidence proportion of clinically relevant non-major (CRNM) bleeding events Baseline, up to 41 months CRNM bleeding is defined as bleeding that does not meet the criteria for major bleeding according to Schulman et al. but is associated with the need for medical intervention and/or personal contact with a physician and/or hospitalization or increase in level of care.
Major (according to Schulman et al.) and/or CRNM bleeding events. Baseline, up to 41 months Incidence proportion of major (according to Schulman et al.) and/or CRNM bleeding events.
Any bleeding event. Baseline, up to 41 months Incidence proportion of any bleeding event.
Overall response rate (ORR) Baseline, up to 41 months ORR is defined as proportion of patients with any response (partial or complete remission) overall.
Progression-free survival (PFS) Baseline, up to 41 months Time from start of acalabrutinib to occurrence of progressive disease or death from any cause, whichever comes first.
Overall survival (OS) Baseline, up to 41 months OS is defined as time from first administration of acalabrutinib to death from any cause.
Therapy decision making Baseline Frequencies of parameters affecting therapy choice.
Previous therapies Baseline Frequencies and percentages of previous therapies
Acalabrutinib (+/- obinutuzumab) treatment: Duration Baseline, up to 41 months Analysis of treatment duration of acalabrutinib using descriptive statistics.
Acalabrutinib (+/- obinutuzumab) treatment: Dose intensity Baseline, up to 41 months Analysis of dose intensity of acalabrutinib treatment with reference to the SmPC (absolute and relative) using descriptive statistics.
Obinutuzumab treatment: Duration Baseline, up to 41 months Analysis of treatment duration of obinutuzumab using descriptive statistics
Reasons for end of treatment of obinutuzumab Baseline, up to 41 months Frequencies and percentages of reasons for end of obinutuzumab treatment.
Types of DOAC Baseline, up to 41 months Type of DOAC used (edoxaban, rivaroxaban, dabigatran and apixaban).
Reasons for DOAC treatment Baseline, up to 41 months Frequencies and precentages of reasons for DOAC treatment.
DOAC treatment: Duration Baseline, up to 41 months Analysis of DOAC treatment duration using descriptive statistics.
DOAC treatment: Dose modifications Baseline, up to 41 months Frequencies and percentages of dose modifications of DOAC treatment.
DOAC treatment: Reasons for dose modifications Baseline, up to 41 months Frequencies and percentages of reasons for dose modifications of DOAC treatment.
DOAC treatment: Reasons for end of treatment Baseline, up to 41 months Frequencies and percentages of reasons for end of DOAC treatment.
Time from onset to DOAC to start of acalabrutinib Baseline, up to 41 months Assessment of time from onset of DOAC to start of acalabrutinib therapy using descriptive statistics.
Concomitant medication Baseline, up to 41 months Frequency of concomitant medication other than DOAC.
Trial Locations
- Locations (1)
Prof. Dr. Fenchel & Dr. Winkler MVZ Träger GbR
🇩🇪Saalfeld, Thüringen, Germany