Pentostatin, Cyclophosphamide, and Rituximab in Treating Patients With Previously Untreated Chronic Lymphocytic Leukemia

OBJECTIVES:

• To determine the frequency of response in patients with previously untreated, intermediate- or high-risk B-cell chronic lymphocytic leukemia (CLL) treated with pentostatin, cyclophosphamide, and rituximab.
• To characterize the toxicity of this regimen in these patients.

OUTLINE: Patients receive cyclophosphamide IV followed by pentostatin IV on day 1 in course 1. Beginning in course 2 and in all subsequent courses, patients receive cyclophosphamide IV on day 1, pentostatin IV on day 1, and rituximab IV on day 1 or on days 1 and 2. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at least every 3 months for 1 year.

DISEASE CHARACTERISTICS:

• Diagnosis of chronic lymphocytic leukemia (CLL), as evidenced by an absolute lymphocytosis in the blood of at least 5,000 lymphocytes per microliter OR bone marrow lymphocytosis ≥ 30% of all nucleated cells

• Previously untreated disease
• Meets 1 of the following risk criteria as defined by the three-stage Rai system

• Intermediate-risk disease

• Must meet the criteria for active disease as defined by the NCI Working Group guidelines including the following:

• Weight loss
• Fatigue
• Fevers
• Evidence of progressive marrow failure
• Splenomegaly
• Progressive lymphadenopathy
• Progressive lymphocytosis with a rapid doubling time
• High-risk disease
• Malignant lymphocytes must demonstrate B-cells via immunophenotypic or immunohistochemical analysis
• Patients with small lymphocytic lymphoma (CLL type) are eligible

PATIENT CHARACTERISTICS:

Inclusion criteria

• Karnofsky performance status 60-100%
• Total bilirubin ≤ 2.0 mg/dL (patients with Gilbert disease or autoimmune hemolytic anemia should have an evaluation for other causes of hyperbilirubinemia, but if none are found they may be enrolled regardless of serum bilirubin)
• Total creatinine ≤ 2.0 mg/dL OR creatinine clearance > 50 mL/min
• Not pregnant or nursing
• Fertile patients must use effective contraception
• Patients with autoimmune hemolytic anemia or autoimmune thrombocytopenia are eligible for treatment on this protocol regardless of disease stage

Exclusion criteria

• Significant active infections
• Ongoing hepatitis B infection, specifically hepatitis B antigen or surface antigen positivity

• Patients who are hepatitis B antibody positive are eligible for this protocol

PRIOR CONCURRENT THERAPY:

• Concurrent prednisone allowed provided it is used as brief courses (≤ 7 days) for inflammatory conditions unrelated to CLL
• No prior cytotoxic therapy or rituximab for this cancer
• No concurrent radiotherapy or other chemotherapy