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

Inclusion criteria

• Age ≥18 years at the screening visit.
• Has given written consent to participate in the study.
• Has B-cell lymphoma refractory to or intolerant of established therapy known to provide clinical benefit for their condition and having received rituximab as a single agent or in combination with other therapies.
• Disease status requirement: Measurable disease defined as the presence of ≥ 1 nodal lesion that measures ≥ 1.5 cm in a single dimension as assessed by X-ray Computed Tomography (CT) (Positron Emission Tomography (PET/CT), or magnetic resonance imaging [MRI]
• Eastern Co-operative Oncology Group (ECOG) performance status of ≤ 2.
• For men and women of child-bearing potential, willing to use adequate contraception

Exclusion criteria

• Subject is a chronic alcoholic (intake > 35 units of alcohol (>5 bottles of wine weekly)) or drug abuser
• 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
• 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
• 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
• Has had an allogeneic stem cell transplant with current active graft-versus-host-disease.
• Has known active central nervous system involvement of the malignancy.
• Has active, serious infection requiring systemic therapy. Patients may receive prophylactic antibiotics and antiviral therapy at the discretion of the treating physician.
• Has a positive test for human immunodeficiency virus (HIV) antibodies.
• Has active hepatitis B or C. Patients with serologic evidence of prior exposure are eligible.
• 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
• 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.