An Open-Label Phase 2 Study of Ofatumumab (Arzerra) in Combination With Oral GSK2110183 in the Treatment of Relapsed and Refractory Chronic Lymphocytic Leukemia (CLL)

Inclusion Criteria: * Patients must fulfill all of the following criteria to be eligible for admission to the study: * A confirmed diagnosis of B-cell CLL by IWCLL 2008 criteria (Appendix 1) * Patients must have evidence of disease progression as evidenced by rapid doubling of peripheral lymphocyte count, progressive lymphadenopathy or hepatosplenomegaly, worsening anemia or thrombocytopenia, or progressive constitutional symptoms \[including fatigue, weight loss, night sweats, fever (without infection)\] * Must be relapsed or refractory to at least one prior fludarabine-containing regimen (no maximum number of prior regimens). * Age \> 18 years. * ECOG performance status of 0, 1 or 2 (Appendix 3) * Signed the Informed Consent form * Life expectancy of ≥ 6 months * Able to swallow and retain oral medication * Normal HbA1C ≤ 0.07 * Fasting blood sugar \< 7mmol/L Exclusion Criteria: * Subjects meeting any of the following criteria are excluded from this study: * CLL therapy, including stem cell transplantation, within 4 weeks of study initiation. Corticosteroids alone may be administered up to seven days prior to the first dose of study drug. * Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half lives or 4 weeks prior to enrollment, whichever is longer, or currently participating in any other interventional clinical study * Prior treatment with anti-CD20 monoclonal antibody or alemtuzumab within 3 months prior to start of therapy * Known hypersensitivity to ofatumumab, GSK2110183, or any components therein. * Anticoagulants are permitted only if the subject meets PTT and INR entry criteria (INR and PTT ≤ 1.5 times upper normal limit). Their use must be monitored in accordance with local institutional practice. * Current use of any anti-platelet agent (e.g. dipyridamole, clopidogrel) other than aspirin (81mg daily). * Current use of a prohibited medication based on potential drug-drug interaction - a complete list is found in Appendix 1 * Known CNS involvement with CLL * Transformation to aggressive B-cell malignancy (e.g. large B-cell lymphoma, Richter's syndrome, prolymphocytic leukemia \[PLL\]) * "Active" autoimmune disease - prior history of autoimmune hemolysis (DAT positive or negative) or immune thrombocytopenia without current active autoimmune disease is allowed * Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable non-hepatitis B or C chronic liver disease per investigator assessment - please see below for Hepatitis B and C criteria) * Previously diagnosed diabetes mellitus (Type 1 or 2) * Other past or current malignancy. Subjects who have been free of malignancy for at least 5 years, or have a history of completely resected non-melanoma skin cancer, or successfully treated in situ carcinoma are eligible. * Chronic or current infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, and tuberculosis. * Any medical condition that would require long-term use (\> 1 month) of systemic corticosteroids during study treatment (excludes topical or inhaled corticosteroid use) * History of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelae * QTc ≥ 470 msec on screening ECG * Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to study entry, congestive heart failure (NYHA III-IV), and arrhythmia unless controlled by therapy, with the exception of extra systoles or minor conduction abnormalities. * Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease which in the opinion of the investigator may represent a risk for the patient. * Any major surgery within the prior 4 weeks. * Known HIV positive * Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HB DNA test will be performed and if positive the subject will be excluded. * Positive serology for hepatitis C (HC) defined as a positive test for HCAb, in which case reflexively perform a HC RIBA immunoblot assay on the same sample to confirm the result * Screening laboratory values: platelets ≤ 30 x 109/L,neutrophils ≤ 0.7 x 109/L,creatinine ≥ 2.0 times upper normal limit, total bilirubin ≥ 1.5 times upper normal limit (unless due to a known history of Gilbert's disease), ALT ≥ 2.5 times upper normal limit, alkaline phosphatase ≥ 2.5 times upper normal limit, INR and PTT ≤ 1.5 times upper normal limit * Pregnant or lactating women. Women of childbearing potential must have a negative pregnancy test at screening. * Women of childbearing potential, including women whose last menstrual period was less than one year prior to screening, unable or unwilling to use adequate contraception from study start to one year after the last dose of protocol therapy. Adequate contraception is defined as intrauterine device, double barrier method or total abstinence. Oral contraceptives are not adequate due to potential drug-drug interaction. * Male subjects unable or unwilling to use adequate contraception methods from study start to one year after the last dose of protocol therapy.