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Completed

NCT Number: NCT05517265

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

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.

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Key information

Conditions

CLL

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Prof. Dr. Fenchel & Dr. Winkler MVZ Träger GbR

Saalfeld, Thuringia, 07318, Germany

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Calquence

Drug

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

Primary outcomes

  1. Incidence proportion of patients with major bleeding event according to Schulman et al.

    Time frame: 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 outcomes

  1. Incidence proportion of clinically relevant non-major (CRNM) bleeding events

    Time frame: 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.

  2. Major (according to Schulman et al.) and/or CRNM bleeding events.

    Time frame: Baseline, up to 41 months

    Incidence proportion of major (according to Schulman et al.) and/or CRNM bleeding events.

  3. Any bleeding event.

    Time frame: Baseline, up to 41 months

    Incidence proportion of any bleeding event.

  4. Incidence proportion of major bleeding according to Ghia et al.

    Time frame: 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.

  5. Time to first Occurrence of major bleeding events

    Time frame: Baseline, up to 41 months

    Time to first occurrence of major (according to Schulman et al.) bleeding events.

  6. Incidence proportion of central nervous system (CNS) bleeding events

    Time frame: Baseline, up to 41 months

    Frequencies of patients with CNS bleeding events.

  7. Patient safety regarding mortality

    Time frame: Baseline, up to 41 months

    Mortality from all causes during acalabrutinib therapy.

  8. Patient safety in terms of interactions with effectiveness of DOAC

    Time frame: Baseline, up to 41 months

    Rate of any new or recurrent ischemic stroke or arterial systemic embolism or venous thromboembolic events.

  9. VTE (venous thromboembolism)-related death

    Time frame: Baseline, up to 41 months

    Incidence proportion of VTE-related death.

  10. Overall response rate (ORR)

    Time frame: Baseline, up to 41 months

    ORR is defined as proportion of patients with any response (partial or complete remission) overall.

  11. Progression-free survival (PFS)

    Time frame: Baseline, up to 41 months

    Time from start of acalabrutinib to occurrence of progressive disease or death from any cause, whichever comes first.

  12. Overall survival (OS)

    Time frame: Baseline, up to 41 months

    OS is defined as time from first administration of acalabrutinib to death from any cause.

  13. Therapy decision making

    Time frame: Baseline

    Frequencies of parameters affecting therapy choice.

  14. Previous therapies

    Time frame: Baseline

    Frequencies and percentages of previous therapies

  15. Acalabrutinib (+/- obinutuzumab) treatment: Duration

    Time frame: Baseline, up to 41 months

    Analysis of treatment duration of acalabrutinib using descriptive statistics.

  16. Acalabrutinib (+/- obinutuzumab) treatment: Dose intensity

    Time frame: Baseline, up to 41 months

    Analysis of dose intensity of acalabrutinib treatment with reference to the SmPC (absolute and relative) using descriptive statistics.

  17. Obinutuzumab treatment: Duration

    Time frame: Baseline, up to 41 months

    Analysis of treatment duration of obinutuzumab using descriptive statistics

  18. Reasons for end of treatment of obinutuzumab

    Time frame: Baseline, up to 41 months

    Frequencies and percentages of reasons for end of obinutuzumab treatment.

  19. Types of DOAC

    Time frame: Baseline, up to 41 months

    Type of DOAC used (edoxaban, rivaroxaban, dabigatran and apixaban).

  20. Reasons for DOAC treatment

    Time frame: Baseline, up to 41 months

    Frequencies and precentages of reasons for DOAC treatment.

  21. DOAC treatment: Duration

    Time frame: Baseline, up to 41 months

    Analysis of DOAC treatment duration using descriptive statistics.

  22. DOAC treatment: Dose modifications

    Time frame: Baseline, up to 41 months

    Frequencies and percentages of dose modifications of DOAC treatment.

  23. DOAC treatment: Reasons for dose modifications

    Time frame: Baseline, up to 41 months

    Frequencies and percentages of reasons for dose modifications of DOAC treatment.

  24. DOAC treatment: Reasons for end of treatment

    Time frame: Baseline, up to 41 months

    Frequencies and percentages of reasons for end of DOAC treatment.

  25. Time from onset to DOAC to start of acalabrutinib

    Time frame: Baseline, up to 41 months

    Assessment of time from onset of DOAC to start of acalabrutinib therapy using descriptive statistics.

  26. Concomitant medication

    Time frame: Baseline, up to 41 months

    Frequency of concomitant medication other than DOAC.

Sponsors and collaborators

Lead sponsor

iOMEDICO AG

Industry

Collaborators

  • AstraZeneca

Registry information

Official study 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).

Acronym: CICERO

Important dates

Study start
2022
Primary completion
2026
Study completion
2026
First posted
Aug 26, 2022
Registry last updated
May 1, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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