A Prospective, Multicenter, Phase-II Trial of Ibrutinib Plus Venetoclax in Patients With Creatinine Clearance >= 30 ml/Min Who Have Relapsed or Refractory Chronic Lymphocytic Leukemia (RR-CLL) With or Without TP53 Aberrations

Inclusion Criteria: * Documented CLL or SLL requiring treatment according to IWCLL criteria after either being refractory to first line therapy or relapse after initial therapy. * Age at least 18 years. * Adequate bone marrow function defined as: * Absolute neutrophil count (ANC) \>0.75 x 109/L * Platelet count \>30,000 /μL 30 x 109/L. * Hemoglobin \>8.0 g/dL (5 mmol/L) Unless directly attributable to CLL infiltration of the bone marrow, proven by bone marrow biopsy * Creatinine clearance (CrCL) ≥ 30ml/min calculated according to the modified formula of Cockcroft and Gault or directly measured with 24hr urine collection. * Adequate liver function as indicated * Serum aspartate transaminase (AST) or alanine transaminase (ALT) ≤ 3.0 x upper limit of normal (ULN) * Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of nonhepatic origin) * Prothrombin time (PT)/International normal ratio (INR) \<1.5 x ULN and PTT (activated partial thromboplastin time \[aPTT\]) \<1.5 x ULN (unless abnormalities are related to coagulopathy or bleeding disorder). * 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 dose), negative testing for hepatitis C RNA within 42 days prior to registration. * WHO/ECOG performance status 0-3 (appendix C), stage 3 only if attributable to CLL. * Negative pregnancy test at study entry (for women of childbearing potential). * Male and female subjects of reproductive potential must agree to use both a highly effective method of birth control (e.g. implants, injectables, combined oral contraceptives, some intrauterine devices \[IUDs\], complete abstinence , or sterilized partner) and a barrier method (e.g., condoms, cervical ring, sponge, etc.) during the period of therapy and for 90 days after the last dose of study drug. * Ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements. * Written informed consent. Exclusion Criteria: * Any prior therapy with ibrutinib and/or venetoclax. * Transformation of CLL (Richter's transformation). * Patients with a history of confirmed progressive multifocal leukoencephalopathy (PML). * Malignancies other than CLL currently requiring systemic therapies or not being treated in curative intention before or showing signs of progression after curative treatment. * Known allergy to xanthine oxidase inhibitors and/or rasburicase. * Known bleeding disorders (e.g., von Willebrand's disease or hemophilia). * Uncontrolled or active infection. * Patients requiring treatment with a strong cytochrome P450 (CYP) 3A inhibitor (see appendix K). or anticoagulant therapy with warfarin or phenoprocoumon or other vitamin K antagonists. Please note: Patients being treated with NOACs 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. * Major surgery within 28 days prior to registration. * Use of investigational agents which might interfere with the study drug within 28 days prior to registration. * Vaccination with live vaccines within 28 days prior to registration * Steroid therapy within 7 days prior to registration, with the exception of inhaled steroids for asthma, topical steroids, steroids up to 25 mg of prednisolone daily to control autoimmune phenomenon's, or replacement/stress corticosteroids. * Pregnant women and nursing mothers. * Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule.