Sequential Regimen of Bendamustin-Debulking Followed by Ofatumumab and Ibrutinib in CLL Patients (CLL2-BIO)

Inclusion Criteria: 1. Documented CLL requiring treatment (irrespective if first- or relapse treatment) according to International Working Group on CLL (iwCLL) criteria In case of previously treated patients, these 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 CLL2-BIO trial: * chemotherapy within ≥ 28 days * antibody treatment within ≥ 14 days * kinase inhibitors, Bcl-2-antagonists or immunomodulatory agents within ≥ 3 days * corticosteroids may be applied until the start of the BIO-regimen, these have to be reduced to an equivalent of ≤ 20 mg prednisolone during treatment 2. Adequate hematologic function as indicated by a platelet count ≥ 25 x 109/L, a neutrophil count ≥ 1,0 x 109/L and a hemoglobin value ≥ 8.0 g/dL, unless directly attributable to the patient´s CLL (e.g. bone marrow infiltration) 3. Adequate renal function as indicated by a creatinine clearance ≥ 30ml/min calculated according to the modified formula of Cockcroft and Gault or directly measured with 24 hrs urine collection 4. Adequate liver function as indicated by a total bilirubin ≤ 2x, aspartate aminotransferase (AST)/ alanin aminotransferase (ALT) ≤ 2.5x the institutional upper limit of normal (ULN) value, unless directly attributable to the patient's CLL or to Gilbert's Syndrome 5. Negative serological testing for hepatitis B, negative testing for hepatitis-C RNA and negative HIV antibody test within 6 weeks prior to registration 6. Age ≥ 18 years 7. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2, ECOG 3 is only permitted if related to CLL (e.g. due to anemia or severe constitutional symptoms) 8. Life expectancy ≥ 6 months 9. Ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements Exclusion Criteria: 1. Transformation of CLL (i.e. Richter's transformation, pro-lymphocytic leukemia) 2. Known central nervous system (CNS) involvement 3. Patients with confirmed progressive multifocal leukoencephalopathy (PML) 4. Malignancies other than CLL currently requiring systemic therapy 5. Uncontrolled infection requiring systemic treatment 6. Any comorbidity or organ system impairment rated with a cumulative illness rating scale (CIRS) score of 4, excluding the eyes/ears/nose/throat/larynx organ system 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) 7. Use of investigational agents which might interfere with the study drug within 3 days prior to Registration 8. Known hypersensitivity to ofatumumab, ibrutinib or any of the excipients Please note: Patients with a known hypersensitivity to bendamustine are allowed to participate but will not receive a debulking with bendamustine 9. Requirement of treatment with strong CYP3A4-inhibitors/-inducers or anticoagulant with phenprocoumon (marcumar), warfarin, or other vitamin k antagonists 10. History of stroke or intracranial hemorrhage within 6 months prior to registration 11. Pregnant women and nursing mothers (a negative pregnancy test is required for all women of childbearing potential within 7 days before start of treatment and monthly during debulking, induction and maintenance therapy) 12. Fertile men or women of childbearing potential unless: * surgically sterile or ≥ 2 years after the onset of menopause, or * willing to use two methods of reliable contraception including one highly effective (Pearl Index \< 1) and one additional effective (barrier) method during study treatment and for 12 months after end of study treatment. 13. Vaccination with a live vaccine ≤ 28 days prior to registration 14. Legal incapacity 15. Prisoners or subjects who are institutionalized by regulatory or court order 16. Persons who are in dependence to the sponsor or an investigator