To compare the efficacy and safety of combination treatment with Genasense, fludarabine, and rituximab versus combination treatment with fludarabine and rituximab in previously untreated subjects with CLL.

Inclusion Criteria:

• Previously untreated subjects with intermediate-or high-risk CLL(modified Rai Stages I-IV)
• Measurable disease as primarily established by the National Cancer Institute-sponsored Working Group(NCI-WG) Guidelines for the diagnosis of CLL
• Requiring therapy for active disease, as primarily defined by the NCI-WG Guidelines
• Eastern Cooperative Oncology Group Performance Status < 2
• Adequate organ function determined , 14 days prior to the first dose of study medication

Exclusion Criteria:

• Absolute Lymphocyte count > 100,000/uL
• Prior chemotherapy or other therapy for CLL, including allogeneic transplant
• Less than 3 weeks from any prior major surgery at the time of informed consent
• Failure to recover from any serious adverse effect of surgery
• History of autoimmune hemolytic anemia or autoimmune thrombocytopenia
• Active serious infection requiring systemic anti-infective therapy