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Chronic Lymphoid LeukemiaPhase 2CLL-FrailNCT04883749

Efficacy of Acalabrutinib in Very Old or Frail Patients With Treatment-naïve or Relapsed/Refractory CLL

A Phase 2 study testing Acalabrutinib in people with Chronic Lymphoid Leukemia, run by German CLL Study Group at 20 sites in 2 countries.

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 aim of this trial is to show the efficacy, safety and feasibility of acalabrutinib in a cohort of CLL-patients ≥80 years or with a FRAIL scale score >2 (5-item questionnaire to be filled out by the patient) Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Chronic Lymphoid Leukemia
What is being tested?
Acalabrutinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
53 participants
Where
20 sitesin 2 countries
Study dates
1 Jun 2021to 8 May 2025
Phase
Phase 2
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

Who may be able to join

  • Age ≥80 years AND/OR considered too frail for intensive/standard treatment defined by a frailty score of >2 on the FRAIL scale via the patient´s assessment.
  • Have documented CLL requiring treatment according to iwCLL 2018 criteria
  • Ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements
  • Glomerular Filtration Rate (GFR) >30ml/min directly measured with 24hr urine collection, calculated according to the modified formula of Cockcroft and Gault (for men: GFR ≈ ((140 - age) x bodyweight)/ (72 x creatinine), for women x 0, 85) or an equally accurate method (Please note: Patients currently on hemodialysis are excluded from participating in the trial)
  • Adequate liver function as indicated by a total bilirubin ≤ 3 x, Aspartate-Aminotransferase/Alanin-Aminotransferase (AST/ ALT) ≤ 3 x the institutional Upper Limit of Normal (ULN) value, unless directly attributable to the patient's CLL or to Gilbert's Syndrome
  • Adequate marrow function independent of growth factor or transfusion support as follows, unless cytopenia is due to marrow involvement of CLL:
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  • Absolute neutrophil count ≥ 1.0 × 10^9/L
  • Platelet counts ≥ 30 × 10^9/L; in cases of thrombocytopenia clearly due to marrow involvement of CLL (per the discretion of the investigator); platelet count should be ≥ 10 × 10^9/L if there is bone marrow involvement
  • Total haemoglobin ≥ 9 g/dL (without transfusion support, unless anaemia is due to marrow involvement of CLL)
  • Negative serological testing for hepatitis B (HBsAg negative and anti-HBc negative; patients positive for anti-HBc may be included if PCR for HBV DNA is negative and HBV-DNA Polymerase Chain Reaction (PCR) is performed every month until 12 months after last month of treatment), negative testing for hepatitis C RNA within 6 weeks prior to registration
  • Life expectancy ≥ 3 months
  • Maximum of 1 previous treatment for CLL
  • In case of a recent previous treatment, patients must have recovered from acute toxicities and treatment regimen must be stopped within the following time periods before start of the study treatment in the CLL-Frail trial:
  • chemotherapy ≥ 28 days
  • antibody treatment ≥ 14 days
  • kinase inhibitors (see also exclusion criterion 6), BCL2-antagonists or immunomodulatory agents ≥ 3 days
  • corticosteroids may be applied until the start of the study therapy, these have to be reduced to an equivalent of ≤ 20 mg prednisolone per day during treatment
  • Signed informed consent and, in the investigator's judgment, able to comply with the study protocol

Who cannot join

  • >1 prior CLL-specific therapy (except corticosteroid treatment administered due to necessary immediate intervention; within the last 14 days before start of study treatment, only dose equivalents up to 20 mg prednisolone are permitted)
  • Transformation of CLL to aggressive Non-Hodgkin's Lymphoma (NHL) e.g. Richter's transformation or prolymphocytic leukaemia
  • Patients with a history of confirmed progressive multifocal leukoencephalopathy (PML)
  • Patients with uncontrolled autoimmune haemolytic anaemia or immune thrombocytopenia
  • Prior exposure to acalabrutinib
  • Progression during previous treatment with another BTK inhibitor, and/or presence of known mutations associated with resistance to therapy, e.g. Bruton´s Tyrosine Kinase (BTK) and Phospholipase C Gamma 2 (PLCg2)
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  • Uncontrolled concomitant malignancy, i.e. any concomitant malignancy that may compromise the assessment of CLL stage and the response assessment of the study treatment
  • Eastern Cooperative Oncology Group Performance Status (ECOG) performance status >3
  • Uncontrolled or active infection (including positive SARS-Cov-2 PCR result)
  • Patients with known infection with human immunodeficiency virus (HIV)
  • Significant cardiovascular disease such as symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 3 months of screening, or any class 4 cardiac disease as defined by the New York Heart Association Functional Classification at Screening (Please note: Subjects with controlled, asymptomatic atrial fibrillation are allowed to enroll on study)
  • Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months before screening
  • Significantly increased risk of bleeding according to the investigator´s evaluation, e.g. due known bleeding diathesis (e.g. von-Willebrandt´s disease or hemophilia), major surgical procedure ≤ 4 weeks or stroke/intracranial hemorrhage ≤ 6 months
  • Use of investigational agents which might interfere with the study drug within 28 days prior to registration for study screening
  • Requirement of therapy with strong CYP3A4 inhibitors/inducers or anticoagulant with phenprocoumon (marcumar) or other vitamin K-antagonists (Please note: Switch to alternative anticoagulants for vitamin K antagonists is permitted)
  • Inability to swallow tablets
  • Legal incapacity
  • Prisoners or subjects who are institutionalized by regulatory or court order
  • Persons who are in dependence to the sponsor or an investigator

Trial locations and contacts

20 sites in 2 countries.

20 sites in 2 countries

Germany18 sites

  • Onkologische Schwerpunktpraxis Kurfürstendamm

    Berlin, 10707

  • Universitätsklinik Köln

    Cologne, 50937

  • Donau-Isar-Klinikum Deggendorf Hämatologie/Onkologie

    Deggendorf, 94469

  • Oncoresearch Institut für klinische Studien GbR

    Erlangen, 91052

  • Universitaetsklinikum Essen

    Essen, 45147

  • Onkologische Kooperation Harz

    Goslar, 38642

  • OncoResearch Lerchenfeld

    Hamburg, 22081

  • MediProjekt GBR

    Hanover, 30171

  • Universitaetsklinikum Schleswig-Holstein Campus Kiel

    Kiel, 24105

  • Praxis fuer Haematologie und Onkologie

    Koblenz, 56068

  • H.O.T Praxis Landshut

    Landshut, 84036

  • Lübecker Onkologische Schwerpunktpraxis

    Lübeck, 23562

  • Gemeinschaftspraxis Haematologie und Onkologie

    Magdeburg, 39104

  • Gemeinschaftspraxis für Hämatologie und Onkologie

    Münster, 48153

  • Brüderkrankenhaus St. Josef Paderborn

    Paderborn, 33098

  • Gemeinschaftspraxis für Hämatologie und Onkologie

    Ravensburg, 88212

  • Universitaetsklinikum Ulm

    Ulm, 89081

  • Hämatologisch Onkologische Schwerpunktpraxis

    Würzburg, 97080

Other trials in Germany

Austria2 sites

  • Medizinische Universität Innsbruck

    Innsbruck, 6020

  • Hanusch Krankenhaus

    Vienna, 1140

Other trials in Austria

About this study

Official title: CLL-Frail - A Prospective, Multicenter Phase II Trial of Acalabrutinib in Very Old (≥80y) or Frail CLL-Patients

The aim of this trial is to show the efficacy, safety and feasibility of acalabrutinib in a cohort of CLL-patients ≥80 years or with a FRAIL scale score >2 (5-item questionnaire to be filled out by the patient)

Being tested
Acalabrutinib
Keywords
CLL
Medical subject headings
Leukemia, B-Cell

What participants receive

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

  • AcalabrutinibBiological

    Also called Calquence, ACP-196

    Cycle (q28d): Acalabrutinib p.o.100 mg twice daily (BID)

Study groups in NCT04883749
Study groupRoleWhat they receive
AcalabrutinibExperimentalAcalabrutinib will be administered up to 24 cycles (= approx. 24 months total) until progression of disease (PD) or intolerable toxicity
Receives: Biological: Acalabrutinib

What is being measured

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

  1. Overall response rate (ORR) at initial response assessment

    Proportion of patients having achieved complete response (CR), complete response with incomplete bone marrow recovery (CRi) or partial response (PR) as response (according to the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 guidelines)

    Measured: At initial response assessment (approx. 6 months after initiation of therapy)

Secondary outcomes (6)

  1. ORR at final restaging

    Proportion of patients having achieved complete response (CR), complete response with incomplete bone marrow recovery (CRi) or partial response (PR) as response (according to the iwCLL 2018 guidelines)

    Measured: At final restaging (approx. 24 months after initiation of therapy)

  2. Overall survival (OS)

    Time from the date of registration to the date of death due to any cause

    Measured: Up to 24 month

  3. Progression-free survival (PFS)

    Time from the date of registration to the date of first occurrence of disease progression or relapse (according to iwCLL 2018 criteria) or death from any cause, whichever occurs first

    Measured: Up to 24 month

  4. Event-free survival (EFS)

    Time from the date of registration to the first occurrence of progression or relapse (according to iwCLL 2018 criteria), death from any cause or initiation of a subsequent anti-leukemic treatment, whichever occurs first

    Measured: Up to 24 month

  5. Time to next CLL treatment (TTNT).

    Time from date of registration to the date of initiation of subsequent anti-leukemic treatment

    Measured: Up to 24 month

  6. Safety parameters: Adverse events (AE) and adverse events of special interest (AESI)

    Type, frequency, and severity of AEs and AESIs

    Measured: Up to 24 month

Timeline

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

  1. First posted12 May 2021
  2. Study start1 Jun 2021
  3. Primary completion8 May 2025
  4. Study completion8 May 2025

Resources

More details

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

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
53 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04883749
Sponsor's protocol ID
CLL-Frail
Other IDs
2023-507002-14-00, 2020-002142-17, 2023
Acronym
CLL-Frail
Status last verified
Jun 2025
First submitted
7 May 2021
Last updated
8 Jun 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Simon F, Ligtvoet R, Bohn JP, Nosslinger T, von Tresckow J, Liersch R, Gaska T, Jentsch-Ullrich K, Gartner M, Wolff T, Schwaner I, Wolf D, Schneider C, Vehling-Kaiser U, Ritgen M, Spoer C, Eckart M, Decker T, Chakupurakal G, Schottker B, Kisro J, Kreuzer KA, Tausch E, Stilgenbauer S, Robrecht S, Stumpf J, Fink AM, Furstenau M, Fischer K, Goede V, Hallek M, Eichhorst B. Acalabrutinib treatment for older (aged >/=80 years) and/or frail patients with CLL: primary end point analysis of the CLL-Frail trial. Blood. 2025 Dec 25;146(26):3153-3162. doi: 10.1182/blood.2025028550.

    PubMed 40906922

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Acalabrutinib in people with Chronic Lymphoid Leukemia, run by German CLL Study Group at 20 sites in 2 countries.

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 18 inclusion and 19 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 8 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in Germany, Austria. 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.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

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?

Overall response rate (ORR) at initial response assessment (time frame: At initial response assessment (approx. 6 months after initiation of therapy)). 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 NCT04883749, which also lists 1 linked publication.

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 8 Jun 2025.

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