A Pilot Study on Intermittent Ibrutinib in Patients With Advanced-phase Chronic Lymphocytic Leukemia (CLL)

Inclusion Criteria: 1. Ability to understand and voluntarily provide written informed consent and comply with the requirements of the study. 2. Age 18 years and older. There is no upper age limit in this trial. 3. Able to adhere to the study visit schedule and other protocol requirements. 4. Before start ibrutinib for the first time: diagnosed with CLL/SLL and active disease in need of treatment after having failed chemoimmunotherapy for CLL defined as a) refractory according to iwCLL criteria; or b) relapsed and deemed not suitable for additional chemo- or chemoimmunotherapy or c) del 17p and/or TP53 mutation irrespective of prior therapy. 5. Having received at least 6 months of ibrutinib therapy and having achieved at least clinical PR according to IWCLL criteria. 6. ECOG performance status of \</= 2 at screening. 7. Laboratory test results: * Absolute neutrophil count \>/= 0.5 x 109/L * Platelet count \>/= 30 x 109/L * Serum creatinine \< 177 µmol/L * ASAT (SGOT) and ALAT (SGPT) \>/= 2 x ULN or \>/= 5 x ULN unless attributable to CLL/SLL 8. Disease free of prior malignancies for \>/= 2 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast. 9. Agree to use reliable forms of contraception. Post-menopausal females and surgically sterilized females are exempt from this criterion. Exclusion Criteria: 1. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form. 2. Pregnant or breast feeding females. 3. Any condition, including the presence of laboratory abnormalities, which according to the responsible physician places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study. 4. Use of any other experimental therapy within the last 14 days. 5. Concurrent use of other anti-cancer agents or treatments than ibrutinib (except a low dose of corticosteroids, max 10 mg of prednisone/day). 6. Positivity for HIV or infectious hepatitis, type A, B or C. 7. Opportunistic infections within the last 3 months. 8. Patient planned for or being a potential candidate for allo-SCT. 9. Uncontrolled hemolytic anemia or autoimmune thrombocytopenia. 10. CNS involvement or history of Richter's transformation. 11. Requires or has received anticoagulation treatment with warfarin or equivalent Vitamin K antagonists (eg, phenprocoumon) within 28 days of the first dose of ibrutinib. 12. Requires treatment with a strong cytochrome P450 (CYP) 3A4/5 inhibitor.