Forodesine hydrochloride will be administered orally at a dose of 200 mg daily for 7 days each week for 4 weeks (cycle number 1). The drug will be administered once daily one hour prior to or two hours after meals. Patients will be evaluated after 1 full cycle of therapy (28 days).

Inclusion Criteria:

• Ages 18 years and older
• Diagnosis of CLL established by peripheral blood and bone marrow examination and using the standard criteria
• Patients with Rai stage III or IV, or earlier stage with massive, symptomatic lymphadenopathy requiring therapy
• Primary resistance to fludarabine-based therapy (no complete response [CR] or partial response [PR]) or progressive disease within 6 months of response to prior fludarabine containing regimen.
• ECOG performance status of 0, 1, 2 or 3
• Willing to take adequate contraception (i.e. latex condom, cervical cap, diaphragm, abstinence, etc.) for the entire duration of the study and 3 months after
• All investigational treatments should have been discontinued for at least 1 week prior to the initiation of the study drug.

Exclusion Criteria:

• Pregnant or nursing
• Unable or unwilling to sign consent
• Severe, ongoing co-morbid conditions, which would preclude safe delivery of the investigational therapy
• Active serious infections that are not controlled by antibiotics
• ECOG performance status 4
• Inadequate renal function: creatinine 2.0 or more unless related to the disease
• Inadequate liver function: bilirubin 3.0 or more, transaminases 3 x upper limit of normal or more unless related to the disease
• Known positive test for HIV
• Patients with known hepatitis B and/or hepatitis C active infection