This research study measures the safety and efficacy of the combination of three drugs that are approved, Nipent, Rituxan and Cytoxan in the treatment of Chronic Lymphocytic Leukemia (CLL). These drugs are being given together for investigational purposes as the specific combination of these three drugs has not been approved for treatment of CLL by the FDA.

Chronic Lymphocytic Leukemia (CLL) is the most common form of adult leukemia in the U.S. Recent experience with Nipent in conjunction with Rituxan has shown that this combination is well tolerated and is clinically promising. It is expected that the addition of Cytoxan in patients with previously untreated CLL and patients who have relapsed or failed prior therapy may benefit from combined therapy using Nipent, Cytoxan and Rituxan. It is unknown how the addition of Cytoxan will affect the toxicity profile of the Rituxan and Nipent regimen, however, patients will be monitored for toxicities. It is expected that bone marrow toxicities will not increase to unreasonable levels.

The primary objective of the study is to determine the overall efficacy response rate following treatment with Nipent, Cytoxan and Rituxan of patients with previously untreated or treated CLL. The secondary objectives of the study are to determine the duration of response, time to progression, time to treatment failure and to evaluate the toxicity of this combination of drugs and the incidence and severity of adverse events.

Inclusion Criteria:

• Stage II, III or IV Chronic Lymphocytic Leukemia
• Disease requires chemotherapeutic treatment
• CT or MRI scan confirming measurable tumor size
• Documentation of CD markers
• Up to one prior treatment regimen
• Expected survival greater than 6 months
• ECOG performance status of 0-2
• Adequate renal, bone marrow and liver functions
• Negative pregnancy test (females of childbearing potential)
• Must agree to use acceptable birth control, if fertile
• Must complete Informed Consent
• No heart disease and must have adequate cardiac function
• Must test negative for viral Hepatitis B and C

Exclusion Criteria:

• More than one prior treatment for Chronic Lymphocytic Leukemia
• Known sensitivity to Nipent, Rituxan or Cytoxan or any component of these drugs
• Known HIV or AIDS illness
• Thyroid disease requiring medication
• History of any malignancy that could affect the diagnosis or assessment of the study treatment
• Pregnancy or breast feeding
• Evidence of Hepatitis B or C infection
• Inability to comply with the requirements of the study