The Safety, Pharmacokinetic and Pharmacodynamic Effect of KA2237 (PI3 Kinase p110β/δ Inhibitor) In B Cell Lymphoma

Exclusion Criteria

• •1. Subject is a chronic alcoholic (intake \> 35 units of alcohol (\>5 bottles of wine weekly)) or drug abuser
• •2. Subject has any medical or psychiatric condition that, in the opinion of the Investigator, may compromise the subject's ability to participate in this study
• •3. Female subjects who are breastfeeding, pregnant, or plan to become pregnant during the study or within 3 months following the last dose of investigational product
• •4. Subjects with a current or recent history, as determined by the Investigator, of severe, progressive, and/or uncontrolled renal disease (estimated glomerular filtration rate (eGFR) \<30ml/min), hepatic (Alanine transaminase (ALT) 2.5 times upper limit of normal (\>2.5xULN), bilirubin \> 2x ULN), hematological (absolute neutrophil count (ANC) \<1.0 x 109/L, platelet count \<75x109/L or requires regular platelet transfusions to maintain a platelet count ≥ 75 x 109/L , hemoglobin \<9g/dL), endocrine (glycated Haemoglobin (HbA1c)\>7% or random glucose \>200mg/dL), pulmonary (Forced Expiratory Volume in 1 second (FEV1) \<70% of predicted value), cardiac (New York Heart Association (NYHA)) class III/IV, or neurological disease
• •5. Has had an allogeneic stem cell transplant with current active graft-versus-host-disease.
• •6. Has known active central nervous system involvement of the malignancy.
• •7. Has active, serious infection requiring systemic therapy. Patients may receive prophylactic antibiotics and antiviral therapy at the discretion of the treating physician.
• •8. Has a positive test for human immunodeficiency virus (HIV) antibodies.
• •9. Has active hepatitis B or C. Patients with serologic evidence of prior exposure are eligible.
• •10. Disease-related exclusions
• •* Had treatment with a short course of corticosteroids (\> 10mg daily prednisone equivalents) for symptom relief within 1-week prior to screening.
• •* Has poorly controlled diabetes mellitus (HbA1c \>7% or random glucose \>200mg/dL)
• •* Known tuberculosis (TB) disease or latent TB infection
• •* Has chronic, active colitis
• •11. Medication related exclusions
• •* Had alemtuzumab therapy within 12-weeks prior to screening.
• •* Has taken a medication that is a potent inhibitor or inducer of cytochrome P450 3A4 (CYP3A4) within 1-week prior to screening.
• •* The subject has previously participated in this study.
• •* The subject has participated or is currently participating in another study of an investigational medicine or medical device (radiotherapy, radio-immunotherapy, biological therapy, chemotherapy), within 4-weeks prior to screening.