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CLLCICERONCT05517265

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

An observational study of CLL, run by iOMEDICO AG at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
CLL
What is being tested?
Calquence
How many people
45 participants
Where
1 siteGermany
Study dates
12 Oct 2022to 20 Mar 2026
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Study population: Adult patients with CLL receiving acalabrutinib (+/- obinutuzumab) and co-medication with DOAC.

Who may be able to join

  • 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.

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

Germany1 site

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

    Saalfeld, Thuringia, 07318

Other trials in Germany

About this study

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).

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.

Read the 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.

Conditions
CLL
Being tested
Calquence
Keywords
CLL, Acalabrutinib (+/- Obinutuzumab), DOAC

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CalquenceDrug

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

  • CalquenceDrug

    acalabrutinib according to Calquence® SmPC.

Study groups in NCT05517265
Study groupRoleWhat they receive
first-line therapyPatients enrolled for first-line acalabrutinib (+/- obinutuzumab).
Receives: Drug: Calquence
later-line therapyPre-treated patients enrolled for later-line acalabrutinib therapy.
Receives: Drug: Calquence

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline until end of acalabrutinib treatment (+ 30 days safety follow-up); up to 41 months

Secondary outcomes (26)

  1. 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.

    Measured: Baseline, up to 41 months

  2. 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.

    Measured: Baseline, up to 41 months

  3. Any bleeding event.

    Incidence proportion of any bleeding event.

    Measured: Baseline, up to 41 months

  4. 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.

    Measured: Baseline, up to 41 months

  5. Time to first Occurrence of major bleeding events

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

    Measured: Baseline, up to 41 months

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

    Frequencies of patients with CNS bleeding events.

    Measured: Baseline, up to 41 months

  7. Patient safety regarding mortality

    Mortality from all causes during acalabrutinib therapy.

    Measured: Baseline, up to 41 months

  8. 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.

    Measured: Baseline, up to 41 months

  9. VTE (venous thromboembolism)-related death

    Incidence proportion of VTE-related death.

    Measured: Baseline, up to 41 months

  10. Overall response rate (ORR)

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

    Measured: Baseline, up to 41 months

  11. Progression-free survival (PFS)

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

    Measured: Baseline, up to 41 months

  12. Overall survival (OS)

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

    Measured: Baseline, up to 41 months

  13. Therapy decision making

    Frequencies of parameters affecting therapy choice.

    Measured: Baseline

  14. Previous therapies

    Frequencies and percentages of previous therapies

    Measured: Baseline

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

    Analysis of treatment duration of acalabrutinib using descriptive statistics.

    Measured: Baseline, up to 41 months

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

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

    Measured: Baseline, up to 41 months

  17. Obinutuzumab treatment: Duration

    Analysis of treatment duration of obinutuzumab using descriptive statistics

    Measured: Baseline, up to 41 months

  18. Reasons for end of treatment of obinutuzumab

    Frequencies and percentages of reasons for end of obinutuzumab treatment.

    Measured: Baseline, up to 41 months

  19. Types of DOAC

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

    Measured: Baseline, up to 41 months

  20. Reasons for DOAC treatment

    Frequencies and precentages of reasons for DOAC treatment.

    Measured: Baseline, up to 41 months

  21. DOAC treatment: Duration

    Analysis of DOAC treatment duration using descriptive statistics.

    Measured: Baseline, up to 41 months

  22. DOAC treatment: Dose modifications

    Frequencies and percentages of dose modifications of DOAC treatment.

    Measured: Baseline, up to 41 months

  23. DOAC treatment: Reasons for dose modifications

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

    Measured: Baseline, up to 41 months

  24. DOAC treatment: Reasons for end of treatment

    Frequencies and percentages of reasons for end of DOAC treatment.

    Measured: Baseline, up to 41 months

  25. Time from onset to DOAC to start of acalabrutinib

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

    Measured: Baseline, up to 41 months

  26. Concomitant medication

    Frequency of concomitant medication other than DOAC.

    Measured: Baseline, up to 41 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Aug 2022
  2. Study start12 Oct 2022
  3. Primary completion20 Mar 2026
  4. Study completion20 Mar 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
45 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05517265
Sponsor's protocol ID
IOM-100473
Acronym
CICERO
Status last verified
Apr 2026
First submitted
19 Aug 2022
Last updated
1 May 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 15842354

  • 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.

    PubMed 32459600

Questions about this trial

What is this clinical trial studying?

An observational study of CLL, run by iOMEDICO AG at 1 site in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05517265, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 May 2026.

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