A Phase I/II, Open-label Study of Ofatumumab Added to Chlorambucil in Previously Untreated Japanese Patients With Chronic Lymphocytic Leukemia

Exclusion Criteria

• •Prior immuno- or chemotherapy for CLL or small lymphocytic lymphoma (SLL) with any agent except corticosteroids used to treat autoimmune hemolytic anemia.
• •Previous autologous or allogeneic stem cell transplantation.
• •Active autoimmune hemolytic anemia (AIHA) requiring corticosteroid therapy \> 100 mg/day equivalent to hydrocortisone, or chemotherapy.
• •Known transformation of CLL (e.g. Richter).
• •Known CNS involvement of CLL.
• •Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis and active Hepatitis C.
• •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.
• •Clinically significant cardiac disease including unstable angina, acute myocardial infarction within 6 months prior to screening (Visit 1), congestive heart failure, and arrhythmia requiring therapy, with the exception of extra systoles or minor conduction abnormalities.
• •History of significant cerebrovascular disease or event with significant symptoms or sequelae\*.
• •Glucocorticoid use, unless given in doses ≤ 100 mg/day hydrocortisone (or equivalent dose of other glucocorticoid) for \<7 days for exacerbations other than CLL (e.g. asthma).
• •Known HIV positive.
• •Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb and/or HBsAb positive, an HBV DNA test will be performed and if positive the subject will be excluded.
• •Screening laboratory values :
• •Creatinine \> 2.0 times upper normal limit (unless normal creatinine clearance). Total bilirubin \> 2.0 times upper normal limit (unless due to Gilbert's syndrome).
• •Alanine transaminase (ALT) \> 3.0 times upper normal limit.
• •Previous treatment or known or suspected hypersensitivity to ofatumumab that in the opinion of the investigator or medical monitor is a contraindication to their participation in the present study.
• •Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half lives or 4 weeks prior to Visit 1, whichever is longer, treatment with any anti-CD20 monoclonal antibody within 3 months of Visit 1, or participation in any other interventional clinical study. Note: Participation in any other interventional clinical study after disease progression during post PD-follow-up is permitted.
• •Known or suspected inability to comply with study protocol.
• •Lactating women, women with a positive pregnancy test at Visit 1 or women (of childbearing potential) as well as men with partners of childbearing potential, who are not willing to use adequate contraception from study start through one year following last treatment dose. Adequate contraception is defined as oral hormonal birth control, intrauterine device, male partner sterilization (if male partner is sole partner for that subject) and the double barrier method (condom or occlusive cap plus spermicidal agent).