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

Sponsor
German CLL Study Group (Other)
Overall Status
Recruiting
CT.gov ID
NCT04883749
Collaborator
(none)
50
Enrollment
20
Locations
1
Arm
39
Anticipated Duration (Months)
2.5
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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)

Condition or Disease Intervention/Treatment Phase
  • Biological: Acalabrutinib
 Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
50 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
CLL-Frail - A Prospective, Multicenter Phase II Trial of Acalabrutinib in Very Old (≥80y) or Frail CLL-Patients
Actual Study Start Date :
Jun 1, 2021
Anticipated Primary Completion Date :
Mar 1, 2023
Anticipated Study Completion Date :
Sep 1, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Acalabrutinib

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

Biological: Acalabrutinib
Cycle (q28d): Acalabrutinib p.o.100 mg twice daily (BID)
Other Names:
  • Calquence
  • ACP-196

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Overall response rate (ORR) at initial response assessment [At initial response assessment (approx. 6 months after initiation of therapy)]

      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)

    Secondary Outcome Measures

    1. ORR at final restaging [At final restaging (approx. 24 months after initiation of therapy)]

      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)

    2. Overall survival (OS) [Up to 24 month]

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

    3. Progression-free survival (PFS) [Up to 24 month]

      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

    4. Event-free survival (EFS) [Up to 24 month]

      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

    5. Time to next CLL treatment (TTNT). [Up to 24 month]

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

    6. Safety parameters: Adverse events (AE) and adverse events of special interest (AESI) [Up to 24 month]

      Type, frequency, and severity of AEs and AESIs

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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 × 109/L; in cases of thrombocytopenia clearly due to marrow involvement of CLL (per the discretion of the investigator); platelet count should be ≥ 10 × 109/L if there is bone marrow involvement

    • Total haemoglobin ≥ 9 g/dL (without transfusion support, unless anaemia is due to marrow involvement of CLL)

    1. 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

    2. Life expectancy ≥ 3 months

    3. Maximum of 1 previous treatment for CLL

    4. 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

    1. 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Medizinische Universität Innsbruck Innsbruck Austria 6020
    2 Hanusch Krankenhaus Wien Austria 1140
    3 Onkologische Schwerpunktpraxis Kurfürstendamm Berlin Germany 10707
    4 Donau-Isar-Klinikum Deggendorf Hämatologie/Onkologie Deggendorf Germany 94469
    5 Oncoresearch Institut für klinische Studien GbR Erlangen Germany 91052
    6 Universitaetsklinikum Essen Essen Germany 45147
    7 Onkologische Kooperation Harz Goslar Germany 38642
    8 OncoResearch Lerchenfeld Hamburg Germany 22081
    9 MediProjekt GBR Hannover Germany 30171
    10 Universitaetsklinikum Schleswig-Holstein Campus Kiel Kiel Germany 24105
    11 Praxis fuer Haematologie und Onkologie Koblenz Germany 56068
    12 Universitätsklinik Köln Köln Germany 50937
    13 H.O.T Praxis Landshut Landshut Germany 84036
    14 Lübecker Onkologische Schwerpunktpraxis Lübeck Germany 23562
    15 Gemeinschaftspraxis Haematologie und Onkologie Magdeburg Germany 39104
    16 Gemeinschaftspraxis für Hämatologie und Onkologie Muenster Germany 48153
    17 Brüderkrankenhaus St. Josef Paderborn Paderborn Germany 33098
    18 Gemeinschaftspraxis für Hämatologie und Onkologie Ravensburg Germany 88212
    19 Universitaetsklinikum Ulm Ulm Germany 89081
    20 Hämatologisch Onkologische Schwerpunktpraxis Würzburg Germany 97080

    Sponsors and Collaborators

    • German CLL Study Group

    Investigators

    • Principal Investigator: Barbara Eichhorst, Prof., Department I of Internal Medicine, University Hospital Cologne

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    German CLL Study Group
    ClinicalTrials.gov Identifier:
    NCT04883749
    Other Study ID Numbers:
    • CLL-Frail
    • 2020-002142-17
    First Posted:
    May 12, 2021
    Last Update Posted:
    Mar 22, 2022
    Last Verified:
    Mar 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by German CLL Study Group
    CLL
    Additional relevant MeSH terms:
    Leukemia, Lymphoid
    Leukemia, Lymphocytic, Chronic, B-Cell
    Acalabrutinib

    Study Results

    No Results Posted as of Mar 22, 2022