Low Dose CdA Combined With Valproic Acid (VPA) in Previously Treated B-cell Chronic Lymphocytic Leukemia(B-CLL)

Inclusion Criteria: * B-cell Chronic Lymphocytic Leukemia (CLL) * Patients must have intermediate or high-risk categories of the modified 3-stage Rai and Binet staging * Patient MUST have progressive or symptomatic disease as defined by any of the following conditions: * Progressive lymphocytosis with a lymphocyte count increased \> 50% over the last 2 months period or an anticipation of the doubling time in less than 6 months * Progressive or symptomatic splenomegaly or hepatomegaly * Progressive or symptomatic lymphadenopathy * Evidence of progressive marrow failure as manifested by development or worsening of anemia and/or thrombocytopenia * Presence of any B-symptoms: weight loss ≥ 10% within the previous 6 months, fever \> 38.0°C for ≥ 2 weeks without evidence of infection, or night sweats without evidence of infection * Patient must have received one or more prior therapies for Chronic Lymphocytic Leukemia. Patients may have received any of the following prior treatment regimens: fludarabine-containing combinations, alemtuzumab single agent or combination, rituximab combinations, chlorambucil, cyclophosphamide +/- prednisone, or other forms of immunotherapy… * Patients must have adequate organ function: * Neutrophils \> 500/mm³ * Platelets \> 50.000/mm³ * Creatinine clearance (measured or calculated) \> 40 ml/min * Age \> 18 years * Patient's ECOG performance status must be 0-2 * Patient's written informed consent * Life expectancy \> 6 months Exclusion Criteria: * Patients having received Valproic Acid (VPA) within 3 months * Previous, suspected or known hypersensitivity to VPA, or any of its derivatives * Liver porphyria * Epilepsy due to mitochondrial diseases * Ongoing treatment with VPA-interacting drugs * Cumulative Illness rating Scale (CIRS) \> 6 * Prior allogenic or autologous bone marrow transplantation less than 12 months * Patient having received any anticancer agents (chemotherapy, immunotherapy or targeted agents) within 4 weeks * Central Nervous System involvement * Concomitant disease requiring prolonged use of corticosteroids (\> 1 month) * Transformation into an aggressive B-cell malignancy (e.g. diffuse large cell lymphoma, Hodgkin lymphoma) * Creatinine clearance \< 40 ml/min calculated according to the formula of Cockcroft and Gault. Patients with a calculated creatinine clearance below 40 ml/min may be eligible if (1) a measured creatinine clearance (based on 24 hours urine collection or other reliable method) is \> 40 ml/min, or (2) a new calculation conducted after adequate hydration is \> 40 ml/min. * Any coexisting medical or psychological condition that would preclude participation to the required study procedures * Patient with mental deficiency preventing proper understanding of the requirements of treatment * Pregnancy, lactating woman, females of childbearing potential or male patient who are unwilling to use adequate contraception * Clinically significant auto-immune cytopenia, Coombs-positive hemolytic anemia as judged by the treating physician * Patients with a history of another malignancy in complete remission less than 2 years, except basal cell skin cancer, stage 0 (in situ) cervical carcinoma or tumor treated curatively by surgery * Any severe co-morbidities such as New York Heart Association Class III or IV heart failure, myocardial infarction within 6 months, unstable angina, ventricular tachyarrhythmias requiring ongoing treatment, or severe uncontrolled myocardiopathy, uncontrolled hypertension, severe chronic obstructive pulmonary disease with hypoxemia or uncontrolled diabetes mellitus * Active bacterial, viral or fungal infection * Seropositivity for: Human Immunodeficiency Virus, hepatitis C or hepatitis B (unless clearly due to vaccination) * Liver insufficiency * Total bilirubin \> 2 x the upper limit of normal (ULN) * Prior history of severe hepatic or pancreatic disorder * Alkaline phosphatases and aminotransferases (AST, ALT) \> 2 x ULN