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

NCT04883749 | Completed Phase 2 DMC

• 3 other identifiers: CLL-Frail2023-507002-14-002020-002142-17
• Study Type: interventional
• Target: 53
• Locations: 2 countries
• Sites: 20

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

Keywords

CLL

Outcome Measures

Primary Outcomes (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)

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

Secondary Outcomes (6)

• ORR at final restaging

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

• Overall survival (OS)

  Up to 24 month

• Progression-free survival (PFS)

  Up to 24 month

• Event-free survival (EFS)

  Up to 24 month

• Time to next CLL treatment (TTNT).

  Up to 24 month

Study Arms (1)

Acalabrutinib

EXPERIMENTAL

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

Biological: Acalabrutinib

Interventions

Acalabrutinib BIOLOGICAL

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

Also known as: Calquence, ACP-196

Acalabrutinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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

You may not qualify if:

• \>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)
• 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)

Sponsors & Collaborators

• German CLL Study Group: lead

Study Sites (20)

Medizinische Universität Innsbruck

Innsbruck, 6020, Austria

Location

Hanusch Krankenhaus

Vienna, 1140, Austria

Location

Onkologische Schwerpunktpraxis Kurfürstendamm

Berlin, 10707, Germany

Location

Universitätsklinik Köln

Cologne, 50937, Germany

Location

Donau-Isar-Klinikum Deggendorf Hämatologie/Onkologie

Deggendorf, 94469, Germany

Location

Oncoresearch Institut für klinische Studien GbR

Erlangen, 91052, Germany

Location

Universitaetsklinikum Essen

Essen, 45147, Germany

Location

Onkologische Kooperation Harz

Goslar, 38642, Germany

Location

OncoResearch Lerchenfeld

Hamburg, 22081, Germany

Location

MediProjekt GBR

Hanover, 30171, Germany

Location

Universitaetsklinikum Schleswig-Holstein Campus Kiel

Kiel, 24105, Germany

Location

Praxis fuer Haematologie und Onkologie

Koblenz, 56068, Germany

Location

H.O.T Praxis Landshut

Landshut, 84036, Germany

Location

Lübecker Onkologische Schwerpunktpraxis

Lübeck, 23562, Germany

Location

Gemeinschaftspraxis Haematologie und Onkologie

Magdeburg, 39104, Germany

Location

Gemeinschaftspraxis für Hämatologie und Onkologie

Münster, 48153, Germany

Location

Brüderkrankenhaus St. Josef Paderborn

Paderborn, 33098, Germany

Location

Gemeinschaftspraxis für Hämatologie und Onkologie

Ravensburg, 88212, Germany

Location

Universitaetsklinikum Ulm

Ulm, 89081, Germany

Location

Hämatologisch Onkologische Schwerpunktpraxis

Würzburg, 97080, Germany

Location

Related Publications (1)

• 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.

  PMID: 40906922 DERIVED

Related Links

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

MeSH Terms

Conditions

Leukemia, B-Cell

Interventions

acalabrutinib

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Barbara Eichhorst, Prof.

  Department I of Internal Medicine, University Hospital Cologne

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2021
• First Posted: May 12, 2021
• Study Start: June 1, 2021
• Primary Completion: May 8, 2025
• Study Completion: May 8, 2025
• Last Updated: June 8, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

DE (18); AU (2)