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

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