Clinical Drug Experience Knowledgebase

Criteria

Inclusion Criteria:

Documented CLL requiring treatment according to iwCLL criteria
Age at least 18 years
Life expectancy ≥ 6 months
Ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements
Adequate bone marrow function indicated by a platelet count >30 x10^9/l (unless directly attributable to CLL infiltration of the bone marrow, proven by bone marrow biopsy)
Creatinine clearance ≥70ml/min directly measured with 24hr urine collection or 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). 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 70 ml/min may be eligible if a repeat estimate after adequate hydration is > 70 ml/min
Adequate liver function as indicated by a total bilirubin≤ 2 x, AST/ALT ≤ 2.5 x the institutional ULN value, unless directly attributable to the patient's CLL or to Gilbert's Syndrome
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
Eastern Cooperative Oncology Group Performance Status (ECOG) performance status 0-2

Exclusion Criteria:

Any prior CLL-specific therapies (except corticosteroid treatment administere due to necessary immediate intervention; within the last 10 days before start of study treatment, only dose equivalents of 20 mg prednisolone are permitted).
Transformation of CLL (Richter transformation)
Decompensated hemolysis, defined as ongoing hemoglobin drop in spite of three more concurrent treatments being administered for hemolysis
Detected del(17p) or TP53 mutation
Patients with a history of PML
Any comorbidity or organ system impairment rated with a single CIRS (cumulative illness rating scale) score of 4 (excluding the eyes/ears/nose/throat/larynx organ system), a total CIRS score of more than 6 or any other life-threatening illness, medical condition or organ system dysfunction that, in the investigator´s opinion, could comprise 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)
Urinary outflow obstruction
Malignancies other than CLL currently requiring systemic therapies, not being treated in curative intention 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
Uncontrolled or active infection
Patients with known infection with human immunodeficiency virus (HIV)
Requirement of therapy with strong CYP3A4 and CYP3A5 inhibitors/inducers
Anticoagulant therapy with warfarin or phenoprocoumon, (rotation to alternative anticoagulation is allowed, but note that patients being treated with NOAKs can be included, but must be properly informed about the potential risk of bleeding under treatment with ibrutinib)
History of stroke or intracranial hemorrhage within 6 months prior to registration
Use of investigational agents which might interfere with the study drug within 28 days prior to registration
Vaccination with live vaccines 28 days prior to registration
Major surgery less than 30 days before start of treatment
History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies, known sensitivity or allergy to murine products
Known hypersensitivity to any active substance or to any of the excipients of one of the drugs used in the trial
Pregnant women and nursing mothers (a negative pregnancy test is required for all women of childbearing potential within 7 days before start of treatment; further pregnancy testing will be performed regularly)

Fertile men or women of childbearing potential unless:

surgically sterile or ≥ 2 years after the onset of menopause
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
Legal incapacity
Prisoners or subjects who are institutionalized by regulatory or court order
Persons who are in dependence to the sponsor or an investigator