A Phase II, Open Label, Single Arm, Multicenter Study of Chlorambucil in Japanese Previously Untreated Patients With Chronic Lymphocytic Leukemia

Inclusion Criteria

• Diagnosis of CLL defined by: Circulating B lymphocytes ≥5,000 /μL AND Flow cytometry confirmation of immunophenotype with CD5, CD19, CD20, and CD23 prior to Visit 2.
• Considered inappropriate for fludarabine-based therapy.
• Active disease and indication for treatment based on the IWCLL updated NCI-WG guidelines defined by presenting at least any one of the following conditions: Evidence of progressive marrow failure as manifested by development or worsening of anemia and/or thrombocytopenia.

Massive (i.e. at least 6 cm below the left costal margin) or progressive or symptomatic splenomegaly.

Massive nodes (i.e. at least 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy.

Progressive lymphocytosis with an increase of more than 50% over a two month period or an lymphocyte doubling time of less than 6 months.

A minimum of any one of the following disease-related symptoms must be present: a) Unintentional weight loss ≥10% within the previous six months; b) Fevers >38.0°C for ≥ 2 weeks without evidence of infection; or c) Night sweats for more than 1 month without evidence of infection

• Not been previously treated for CLL (prior autoimmune hemolytic anemia treatment with corticosteroids permitted).
• ECOG Performance Status of 0-2.
• QTc 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, 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 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 aminotransferase (ALT) > 3.0 times upper normal limit.

• 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.
• Known or suspected inability to comply with study protocol.
• Lactating women, women with a positive pregnancy test within 7 days prior to administration of the investigational product 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, and male partner sterilization (if male partner is sole partner for that subject) and the double barrier method (condom or occlusive cap plus spermicidal agent).