|
|
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 |
|
|
|
|
|
Maximum of 1 previous treatment for CLL |
|
|
|
|
|
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 |
|
|
|
|
|
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 |
|
|
|
|
|
within 6 weeks prior to registration |
|
|
|
|
|
Life expectancy ≥ 3 months |
|
|
|
|
|
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 |
|
|
|
|
|
>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
|
|
|
|
|
|
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)
|
|
|
|
|
|
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)
|
|
|
|
|
|
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
|
|
|
|
|
|
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
|
|
|
|
|
|
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
|
|
|
|
|
|
Persons who are in dependence to the sponsor or an investigator
|
|
|
|