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

NCT ID: NCT04883749

Last Updated: 2025-06-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 53 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-01
• Study Completion Date: 2025-05-08

Brief 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)

Conditions

Chronic Lymphoid Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Acalabrutinib

Acalabrutinib will be administered up to 24 cycles (= approx. 24 months total) until progression of disease (PD) or intolerable toxicity

Group Type: EXPERIMENTAL

Acalabrutinib

Intervention Type: BIOLOGICAL

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

Interventions

Acalabrutinib

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

Intervention Type: BIOLOGICAL

Other Intervention Names

Calquence; ACP-196

Eligibility Criteria

Inclusion Criteria

1. 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.

2. Have documented CLL requiring treatment according to iwCLL 2018 criteria

3. Ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements

4. 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)

5. 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

6. Adequate marrow function independent of growth factor or transfusion support as follows, unless cytopenia is due to marrow involvement of CLL:

• 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)

7. 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

8. Life expectancy ≥ 3 months

9. Maximum of 1 previous treatment for CLL

10. 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

11. Signed informed consent and, in the investigator's judgment, able to comply with the study protocol

Exclusion Criteria

1. >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)

2. Transformation of CLL to aggressive Non-Hodgkin's Lymphoma (NHL) e.g. Richter's transformation or prolymphocytic leukaemia

3. Patients with a history of confirmed progressive multifocal leukoencephalopathy (PML)

4. Patients with uncontrolled autoimmune haemolytic anaemia or immune thrombocytopenia

5. Prior exposure to acalabrutinib

6. 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)

7. Uncontrolled concomitant malignancy, i.e. any concomitant malignancy that may compromise the assessment of CLL stage and the response assessment of the study treatment

8. Eastern Cooperative Oncology Group Performance Status (ECOG) performance status >3

9. Uncontrolled or active infection (including positive SARS-Cov-2 PCR result)

10. Patients with known infection with human immunodeficiency virus (HIV)

11. 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)

12. Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months before screening

13. 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

14. Use of investigational agents which might interfere with the study drug within 28 days prior to registration for study screening

15. 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)

16. Inability to swallow tablets

17. Legal incapacity

18. Prisoners or subjects who are institutionalized by regulatory or court order

19. Persons who are in dependence to the sponsor or an investigator

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

German CLL Study Group

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Barbara Eichhorst, Prof.

Role: PRINCIPAL_INVESTIGATOR

Department I of Internal Medicine, University Hospital Cologne

Locations

Medizinische Universität Innsbruck

Innsbruck, , Austria

Hanusch Krankenhaus

Vienna, , Austria

Onkologische Schwerpunktpraxis Kurfürstendamm

Berlin, , Germany

Universitätsklinik Köln

Cologne, , Germany

Donau-Isar-Klinikum Deggendorf Hämatologie/Onkologie

Deggendorf, , Germany

Oncoresearch Institut für klinische Studien GbR

Erlangen, , Germany

Universitaetsklinikum Essen

Essen, , Germany

Onkologische Kooperation Harz

Goslar, , Germany

OncoResearch Lerchenfeld

Hamburg, , Germany

MediProjekt GBR

Hanover, , Germany

Universitaetsklinikum Schleswig-Holstein Campus Kiel

Kiel, , Germany

Praxis fuer Haematologie und Onkologie

Koblenz, , Germany

H.O.T Praxis Landshut

Landshut, , Germany

Lübecker Onkologische Schwerpunktpraxis

Lübeck, , Germany

Gemeinschaftspraxis Haematologie und Onkologie

Magdeburg, , Germany

Gemeinschaftspraxis für Hämatologie und Onkologie

Münster, , Germany

Brüderkrankenhaus St. Josef Paderborn

Paderborn, , Germany

Gemeinschaftspraxis für Hämatologie und Onkologie

Ravensburg, , Germany

Universitaetsklinikum Ulm

Ulm, , Germany

Hämatologisch Onkologische Schwerpunktpraxis

Würzburg, , Germany

Countries

Austria; Germany

References

Simon F, Ligtvoet R, Bohn JP, Nosslinger T, von Tresckow J, Liersch R, Gaska T, Jentsch-Ulrich K, Gartner M, Wolff T, Schwaner I, Wolf D, Schneider C, Vehling-Kaiser U, Ritgen M, Spoer C, Eckart MJ, Decker T, Chakupurakal G, Schottker B, Kisro J, Kreuzer KA, Tausch E, Stilgenbauer S, Robrecht S, Stumpf J, Fink A, Furstenau M, Fischer K, Goede V, Hallek MJ, Eichhorst BF. Acalabrutinib treatment for older (>/=80 years old) and/or frail patients with CLL: primary end point analysis of the CLL-Frail trial. Blood. 2025 Sep 4:blood.2025028550. doi: 10.1182/blood.2025028550. Online ahead of print.

Reference Type: DERIVED

PMID: 40906922 (View on PubMed)

Related Links

https://www.dcllsg.com/cll-frail/

Click here for more information about this study: CLL-Frail (German CLL Study Group)

Other Identifiers

2023-507002-14-00

Identifier Type: CTIS

Identifier Source: secondary_id

2020-002142-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLL-Frail

Identifier Type: -

Identifier Source: org_study_id