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Documented CLL requiring treatment according to iwCLL criteria |
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Age at least 18 years |
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Life expectancy ≥ 6 months |
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Ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements |
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Adequate bone marrow function independent of growth factor or transfusion support within 2 weeks of screening initiation as follows, unless cytopenia is due to CLL |
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Absolute neutrophil count ≥ 1.0 × 109/L |
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Platelet counts ≥ 30 × 109/L; in cases of thrombocytopenia clearly due to CLL (per the discretion of the investigator), platelet count should be ≥ 10 × 109/L |
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Total haemoglobin ≥ 9 g/dL (without transfusion support, unless anaemia is due to CLL) |
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GFR >30ml/min directly measured with 24hr urine collection, calculated according to |
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the modified formula of Cockcroft and Gault (for men: GFR ≈ ((140 - age) x |
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For patients with creatinine values within the normal range the calculation of the clearance is not necessary. Dehydrated patients with an estimated creatinine clearance less than 30 ml/min may be eligible if a repeat estimate after adequate hydration is > 30 ml/min |
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bodyweight)/ (72 x creatinine), for women x 0, 85) or an equally accurate |
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method |
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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 PCR is performed every month until 12 months after last treatment cycle), negative testing for hepatitis C RNA within 6 weeks prior to registration for study screening (i.e. PCR only required when serology was positive) |
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Eastern Cooperative Oncology Group Performance Status (ECOG) performance status 0-2 |
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Adequate liver function as indicated by a total bilirubin ≤ 2 x, AST/ ALT ≤ 2.5 x the |
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institutional ULN value, unless directly attributable to the patient's CLL or |
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to Gilbert's Syndrome |
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Any prior CLL-specific therapies (except corticosteroid treatment administered due to necessary immediate intervention; within the last 10 days before start of study treatment, only dose equivalents up to 20 mg prednisolone are permitted)
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Transformation of CLL (Richter transformation). When Richter transformation is suspected, PET-CT and/or biopsy should be performed to rule out transformation
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Patients with a history of PML
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Malignancies other than CLL currently requiring systemic therapies, not being treated with curative intent before (unless the malignant disease is in a stable remission due to the discretion of the treating physician or showing signs of progression after curative treatment
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Uncontrolled or active infection
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Patients with known infection with human immunodeficiency virus (HIV)
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Requirement of therapy with strong CYP3A4 and CYP3A5 inhibitors/ inducers (incl. up to 7 days prior to study treatment start)
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Anticoagulant therapy with warfarin or phenprocoumon, (alternative anticoagulation is allowed (e.g. DOACs), but patients must be properly informed about the potential risk of bleeding under treatment with ibrutinib)
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An individual organ/ system impairment score of 4 as assessed by the CIRS definition limiting the ability to receive the study treatment or any other life-threatening illness, medical condition or organ system dysfunction that, in the investigator´s opinion, could compromise the patients' safety or interfere with the absorption or metabolism of the study drugs (e.g. inability to swallow tablets or impaired resorption in the gastrointestinal tract)
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History of stroke or intracranial hemorrhage within 6 months prior to registration for study screening
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Known bleeding disorders
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Child B / C liver cirrhosis
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Use of investigational agents which might interfere with the study drug within 28 days prior to registration for study screening
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Vaccination with live vaccines 28 days prior to registration for study screening
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Major surgery less than 30 days before start of study treatment
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History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies, known sensitivity or allergy to murine products
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Known hypersensitivity to any active substance or to any of the excipients of one of the drugs used in the trial
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Pregnant women and nursing mothers (a negative pregnancy test is required for all women of childbearing potential within 7 days before start of study treatment; further pregnancy testing will be performed monthly)
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Fertile men or women of childbearing potential unless
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willing to use two methods of reliable contraception including one highly effective contraceptive method (Pearl Index <1) and one additional effective (barrier) method during study treatment and for 18 months after the end of study treatment
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Legal incapacity
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Prisoners or subjects who are institutionalized by regulatory or court order
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Persons who are in dependence to the sponsor or an investigator
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surgically sterile or ≥ 2 years after the onset of menopause
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