Buparlisib in Patients With Relapsed and Refractory Chronic Lymphocytic Leukemia

Inclusion Criteria: * Previously documented CLL that is recurrent or relapsed after previous therapy and that requires treatment * Age ≥ 18 years * ECOG Performance Status score of 0, 1 or 2 * Patients must have a life expectancy of at least 12 weeks. Those who have previously completed curative treatment of a malignancy other than CLL will be eligible * Patients must have at least ONE of: Lymphocyte count ≥ 10 x 10\^9/L OR at least one pathologically enlarged lymph node (≥ 2 x 2 cm) by CT scan * Previous therapy: Patients must have received at least 1 prior systemic treatment regimen (single agent or combination therapy). There is no upper limit on number of prior regimens. Patients who have received prior autologous or allogeneic stem cell transplantation are eligible. * Patients must have recovered (to ≤ grade 2) from all reversible toxicity related to prior systemic therapy, and have adequate washout from prior chemotherapy and investigational agents defined as the longest of: * two weeks * standard cycle length of prior regimen (e.g. 28 days for FCR) * 5 half-lives for investigational drugs Not permitted: • prior treatment with buparlisib (BKM120) * Patients may have had radiation, provided a minimum of 21 days has elapsed prior to enrollment. Patients must have recovered from any acute toxic effects from radiation prior to registration * Previous surgery is permitted provided that wound healing has occurred and at least 14 days have elapsed if surgery was major * Absolute neutrophil counts (ANC): ≥ 1.0 x 10\^9/L * Platelets ≥ 50/min x 10\^9/L and more than 5 days since last transfusion * Creatinine clearance\* ≥ 50 mL/min * Bilirubin\*\* ≤ 1.5 x upper normal limit (UNL) * Alanine aminotransferase (AST) and aspartate aminotransferase (ALT) ≤ 1.5 x UNL or ≤ 3 x UNL if hepatic involvement with CLL * Potassium and calcium Within normal limits for laboratory (supplementation permitted) * Glucose (fasting) \< 7.8 mmol/L (AND HbA1c ≤ 8% if diabetic) \* Creatinine clearance as calculated by Cockcroft-Gault formula or by 24 hour urine measurement: Females: GFR = 1.04 x (140-age) x weight in kg serum creatinine in μmol/L Males: GFR = 1.23 x (140-age) x weight in kg serum creatinine in μmol/L \*\* Direct if patient known to have Gilbert's syndrome * Patient consent must be obtained according to local Institutional and/or University Human Experimentation Committee requirements * Patients must be accessible for treatment and follow up. Patients registered on this trial must be treated and followed at the participating centre * In accordance with CCTG policy, protocol treatment is to begin within 2 working days of patient registration Exclusion Criteria: * Progression to high grade lymphoma (Richter's transformation) or myelodysplasia * Patients with known hypersensitivity to the study drug or its excipients * The following are exclusions for enrolment on the study: * Pregnant or lactating women. (N.B. All women of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to registration). * Men and women of childbearing potential who do not agree to use adequate contraception: prior to study entry; while taking buparlisib and after completion of study therapy for 12 weeks in men and 4 weeks in women. * Serious illness or medical condition which would not permit the patient to be managed according to the protocol, including, but not limited to: 1. active uncontrolled or serious infection (viral, bacterial or fungal); 2. pulmonary disease requiring oxygen; 3. known HIV infection or other immune deficiency disorders (except for CLL); 4. uncontrolled auto-immune hemolytic anemia (AIHA) or auto-immune thrombocytopenia (ITP) 5. acute or chronic pancreatitis * Uncontrolled or significant cardiovascular disease including: * Myocardial infarction within 12 months * Uncontrolled angina within 6 months * Clinically significant congestive heart failure (eligible if controlled and LVEF ≥ 50%) * Stroke, TIA or other ischemic event within 12 months * Severe cardiac valve dysfunction * Left ventricular ejection fraction \< 50% (only required if symptoms suggestive or history of cardiovascular disease) * Uncontrolled hypertension * Patient has any of the following mood disorders: * Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (e.g. risk of doing harm to self or others) * Score of ≥ 12 on the PHQ-9 questionnaire * Score of ≥ 15 on the GAD-7 mood scale * ≥ CTCAE grade 3 anxiety * Patient selects a positive response of '1,2,3' to question 9 (suicidal ideation) in the PHQ-9 questionnaire * Patients who have received prior buparlisib (BKM120). * Patients with impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of buparlisib (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection). * Patients who are unable to swallow capsules * Patients on strong CYP3A inhibitors/inducers or therapeutic doses of warfarin-like anticoagulants (must have discontinued \> 7 days prior to day 1). Patients may receive low molecular weight heparin if indicated. See Appendix VII for a list of prohibited medications. * Patients on drugs with a known risk to induce Torsades de Pointes * Patients receiving high dose steroid therapy or another immunosuppressive agent. Note: Topical applications (e.g. rash), inhaled sprays (e.g. obstructive airways diseases), eye drops or local injections (e.g. intra-articular) are allowed. Patients who are on stable moderate dose corticosteroid treatment for treatment of conditions other than CLL (\< dexamethasone 4 mg/day, prednisone 25 mg/day) for at least 14 days before start of study treatment are eligible. * Patients with known HIV positivity. * Patients with known CLL involvement of the central nervous system. * Patients with a history of other malignancies, except those which have been curatively treated and require no ongoing therapy