Status:
COMPLETED
Efficacy of Acalabrutinib in Very Old or Frail Patients With Treatment-naïve or Relapsed/Refractory CLL
Lead Sponsor:
German CLL Study Group
Conditions:
Chronic Lymphoid Leukemia
Eligibility:
All Genders
18+ years
Phase:
PHASE2
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 t...
Eligibility Criteria
Inclusion
- 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
- 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
Exclusion
- \>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)
- 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
Key Trial Info
Start Date :
June 1 2021
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
May 8 2025
Estimated Enrollment :
53 Patients enrolled
Trial Details
Trial ID
NCT04883749
Start Date
June 1 2021
End Date
May 8 2025
Last Update
June 8 2025
Active Locations (20)
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1
Medizinische Universität Innsbruck
Innsbruck, Austria, 6020
2
Hanusch Krankenhaus
Vienna, Austria, 1140
3
Onkologische Schwerpunktpraxis Kurfürstendamm
Berlin, Germany, 10707
4
Universitätsklinik Köln
Cologne, Germany, 50937