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| Name | Class |
|---|---|
| AstraZeneca | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| first-line therapy | Patients enrolled for first-line acalabrutinib (+/- obinutuzumab). |
| |
| later-line therapy | Pre-treated patients enrolled for later-line acalabrutinib therapy. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Calquence | Drug | acalabrutinib (+/- obinutuzumab) according to Calquence® SmPC. |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence proportion of patients with major bleeding event according to Schulman et al. | 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. | Baseline until end of acalabrutinib treatment (+ 30 days safety follow-up); up to 41 months |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence proportion of clinically relevant non-major (CRNM) bleeding events | 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. | Baseline, up to 41 months |
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Inclusion Criteria:
Exclusion Criteria:
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Adult patients with CLL receiving acalabrutinib (+/- obinutuzumab) and co-medication with DOAC.
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| Name | Affiliation | Role |
|---|---|---|
| Klaus Fenchel, Prof. Dr. | Onkologische Praxisklinik Hämatologie/ Onkologie und Gerinnungsstörungen | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Prof. Dr. Fenchel & Dr. Winkler MVZ Träger GbR | Saalfeld | Thuringia | 07318 | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 15842354 | Background | 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. | |
| 32459600 |
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| ID | Term |
|---|---|
| C000604908 | acalabrutinib |
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| Calquence |
| Drug |
acalabrutinib according to Calquence® SmPC. |
|
| Major (according to Schulman et al.) and/or CRNM bleeding events. | Incidence proportion of major (according to Schulman et al.) and/or CRNM bleeding events. | Baseline, up to 41 months |
| Any bleeding event. | Incidence proportion of any bleeding event. | Baseline, up to 41 months |
| Incidence proportion of major bleeding according to Ghia et al. | 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. | Baseline, up to 41 months |
| Time to first Occurrence of major bleeding events | Time to first occurrence of major (according to Schulman et al.) bleeding events. | Baseline, up to 41 months |
| Incidence proportion of central nervous system (CNS) bleeding events | Frequencies of patients with CNS bleeding events. | Baseline, up to 41 months |
| Patient safety regarding mortality | Mortality from all causes during acalabrutinib therapy. | Baseline, up to 41 months |
| Patient safety in terms of interactions with effectiveness of DOAC | Rate of any new or recurrent ischemic stroke or arterial systemic embolism or venous thromboembolic events. | Baseline, up to 41 months |
| VTE (venous thromboembolism)-related death | Incidence proportion of VTE-related death. | Baseline, up to 41 months |
| Overall response rate (ORR) | ORR is defined as proportion of patients with any response (partial or complete remission) overall. | Baseline, up to 41 months |
| Progression-free survival (PFS) | Time from start of acalabrutinib to occurrence of progressive disease or death from any cause, whichever comes first. | Baseline, up to 41 months |
| Overall survival (OS) | OS is defined as time from first administration of acalabrutinib to death from any cause. | Baseline, up to 41 months |
| Therapy decision making | Frequencies of parameters affecting therapy choice. | Baseline |
| Previous therapies | Frequencies and percentages of previous therapies | Baseline |
| Acalabrutinib (+/- obinutuzumab) treatment: Duration | Analysis of treatment duration of acalabrutinib using descriptive statistics. | Baseline, up to 41 months |
| Acalabrutinib (+/- obinutuzumab) treatment: Dose intensity | Analysis of dose intensity of acalabrutinib treatment with reference to the SmPC (absolute and relative) using descriptive statistics. | Baseline, up to 41 months |
| Obinutuzumab treatment: Duration | Analysis of treatment duration of obinutuzumab using descriptive statistics | Baseline, up to 41 months |
| Reasons for end of treatment of obinutuzumab | Frequencies and percentages of reasons for end of obinutuzumab treatment. | Baseline, up to 41 months |
| Types of DOAC | Type of DOAC used (edoxaban, rivaroxaban, dabigatran and apixaban). | Baseline, up to 41 months |
| Reasons for DOAC treatment | Frequencies and precentages of reasons for DOAC treatment. | Baseline, up to 41 months |
| DOAC treatment: Duration | Analysis of DOAC treatment duration using descriptive statistics. | Baseline, up to 41 months |
| DOAC treatment: Dose modifications | Frequencies and percentages of dose modifications of DOAC treatment. | Baseline, up to 41 months |
| DOAC treatment: Reasons for dose modifications | Frequencies and percentages of reasons for dose modifications of DOAC treatment. | Baseline, up to 41 months |
| DOAC treatment: Reasons for end of treatment | Frequencies and percentages of reasons for end of DOAC treatment. | Baseline, up to 41 months |
| Time from onset to DOAC to start of acalabrutinib | Assessment of time from onset of DOAC to start of acalabrutinib therapy using descriptive statistics. | Baseline, up to 41 months |
| Concomitant medication | Frequency of concomitant medication other than DOAC. | Baseline, up to 41 months |
| Background |
| 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. |