Acalabrutinib in Patients With Chronic Lymphocytic Leukemia With Direct Oral Anticoagulation (CICERO)

CLL Clinical Trial

— 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).

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05517265
• Other study ID #: IOM-100473
• Status: Recruiting
• Start date: October 12, 2022
• Est. completion date: October 12, 2025

Study information

• Verified date: April 2024
• Source: iOMEDICO AG
• Contact: Daniel Kummer, Dr.
• Phone: +49761152420
• Email: Cicero[@]iomedico.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: October 12, 2025
• Est. primary completion date: October 12, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Calquence
acalabrutinib (+/- obinutuzumab) according to Calquence® SmPC.
• Calquence
acalabrutinib according to Calquence® SmPC.

Locations

Country	Name	City	State
Germany	Prof. Dr. Fenchel & Dr. Winkler MVZ Träger GbR	Saalfeld	Thüringen

Sponsors (2)

Lead Sponsor	Collaborator
iOMEDICO AG	AstraZeneca

Country where clinical trial is conducted

Germany, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 36 months
Secondary	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 36 months
Secondary	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 36 months
Secondary	Any bleeding event.	Incidence proportion of any bleeding event.	Baseline, up to 36 months
Secondary	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 36 months
Secondary	Time to first Occurrence of major bleeding events	Time to first occurrence of major (according to Schulman et al.) bleeding events.	Baseline, up to 36 months
Secondary	Incidence proportion of central nervous system (CNS) bleeding events	Frequencies of patients with CNS bleeding events.	Baseline, up to 36 months
Secondary	Patient safety regarding mortality	Mortality from all causes during acalabrutinib therapy.	Baseline, up to 36 months
Secondary	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 36 months
Secondary	VTE (venous thromboembolism)-related death	Incidence proportion of VTE-related death.	Baseline, up to 36 months
Secondary	Overall response rate (ORR)	ORR is defined as proportion of patients with any response (partial or complete remission) overall.	Baseline, up to 36 months
Secondary	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 36 months
Secondary	Overall survival (OS)	OS is defined as time from first administration of acalabrutinib to death from any cause.	Baseline, up to 36 months
Secondary	Therapy decision making	Frequencies of parameters affecting therapy choice.	Baseline
Secondary	Previous therapies	Frequencies and percentages of previous therapies	Baseline
Secondary	Acalabrutinib (+/- obinutuzumab) treatment: Duration	Analysis of treatment duration of acalabrutinib using descriptive statistics.	Baseline, up to 36 months
Secondary	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 36 months
Secondary	Obinutuzumab treatment: Duration	Analysis of treatment duration of obinutuzumab using descriptive statistics	Baseline, up to 36 months
Secondary	Reasons for end of treatment of obinutuzumab	Frequencies and percentages of reasons for end of obinutuzumab treatment.	Baseline, up to 36 months
Secondary	Types of DOAC	Type of DOAC used (edoxaban, rivaroxaban, dabigatran and apixaban).	Baseline, up to 36 months
Secondary	Reasons for DOAC treatment	Frequencies and precentages of reasons for DOAC treatment.	Baseline, up to 36 months
Secondary	DOAC treatment: Duration	Analysis of DOAC treatment duration using descriptive statistics.	Baseline, up to 36 months
Secondary	DOAC treatment: Dose modifications	Frequencies and percentages of dose modifications of DOAC treatment.	Baseline, up to 36 months
Secondary	DOAC treatment: Reasons for dose modifications	Frequencies and percentages of reasons for dose modifications of DOAC treatment.	Baseline, up to 36 months
Secondary	DOAC treatment: Reasons for end of treatment	Frequencies and percentages of reasons for end of DOAC treatment.	Baseline, up to 36 months
Secondary	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 36 months
Secondary	Concomitant medication	Frequency of concomitant medication other than DOAC.	Baseline, up to 36 months