Randomized Phase II Trial of Pentostatin, Cyclophosphamide, and Rituximab With or Without Concurrent Avastin® for Previously Untreated B-Chronic Lymphocytic Leukemia (CLL)

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Diagnosis of 1 of the following:

- Biopsy proven small lymphocytic lymphoma (SLL)

- Chronic lymphocytic leukemia (CLL)* as evidenced by the following criteria:

- Peripheral blood lymphocyte count > 5,000/mm³ consisting of small to
moderate size lymphocytes

- Immunophenotyping consistent with CLL, defined by the following:

- The predominant population of lymphocytes share both B-cell antigens
(CD19, CD20, or CD23) as well as CD-5 in the absence of other
pan-T-cell markers (CD-3 or CD-2)

- Dim surface immunoglobulin expression

- Exclusively kappa and lambda light chains

- Negative FISH analysis for t(11;14)(IgH/CCND1) on peripheral blood or
tissue biopsy samples NOTE: *Splenomegaly, hepatomegaly, or lymphadenopathy
are not required for the diagnosis of CLL

- Has ≥ 1 of the following indications** for chemotherapy:

- Evidence of progressive marrow failure as manifested by the development of or
worsening anemia (hemoglobin ≤ 11 g/dL) and/or thrombocytopenia (platelet count
≤ 100,000/mm³)

- Symptomatic or progressive lymphadenopathy, splenomegaly or hepatomegaly

- Has ≥ 1 of the following disease-related symptoms:

- Weight loss > 10% within the past 6 months

- Extreme fatigue attributed to CLL

- Fevers > 100.5^oF for 2 weeks without evidence of infection

- Night sweats without evidence of infection

- Progressive lymphocytosis (not due to the effects of corticosteroids) with an
increase of > 50% over a 2-month period or an anticipated doubling time of < 6
months NOTE: **Marked hypogammaglobulinemia or the development of a monoclonal
protein in the absence of any of the above criteria for active disease are not
sufficient indications for study treatment

PATIENT CHARACTERISTICS:

- ECOG performance status 0-3

- Life expectancy ≥ 12 months

- Total bilirubin ≤ 3.0 times upper limit of normal (ULN) (unless due to Gilbert's
disease)

- Direct bilirubin < 1.5 mg/dL (in patients with Gilbert's disease)

- SGOT ≤ 3.0 times ULN (unless due to hepatic involvement by CLL)

- Creatinine ≤ 1.5 times ULN

- Urine protein:creatinine ratio < 1.0 OR < 1 g of protein by 24-hour urine collection

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 12 months after
completion of study treatment

- Willing to provide mandatory blood and tissue samples

- None of the following cardiovascular conditions:

- NYHA class III-IV heart disease

- Myocardial infarction within the past 6 months

- Unstable angina

- Stroke, cerebrovascular accident, or transient ischemic attack within the past 6
months

- Arterial thromboembolic events within the past 12 months

- Clinically significant peripheral vascular disease

- Uncontrolled hypertension, defined as systolic BP > 150 mm Hg or diastolic BP >
100 mm Hg

- Hypertension allowed provided it is controlled with a stable
anti-hypertensive regimen

- History of hypertensive crises or hypertensive encephalopathy

- Deep venous thromboses or pulmonary embolism within the past 12 months

- No evidence of bleeding diathesis or coagulopathy

- No uncontrolled or active hemolytic anemia requiring immunosuppressive therapy or
other pharmacologic treatment

- No active or recent history (within the past 30 days) of hemoptysis (≥ ½ teaspoon of
bright red blood per episode)

- No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within
the past 6 months

- No active peptic ulcer disease

- No serious non-healing wound, ulcer, or bone fracture

- No significant traumatic injury within the past 28 days

- No uncontrolled infection

- No active HIV infection

- No other active primary malignancy (except nonmelanoma skin cancer or carcinoma in
situ of the cervix) requiring treatment or limiting survival to ≤ 2 years

- No psychiatric or addictive disorders or other conditions that, in the opinion of the
investigator, would preclude study participation

PRIOR CONCURRENT THERAPY:

- Prior corticosteroids allowed

- More than 4 weeks since prior radiotherapy

- More than 28 days since prior and no concurrent major surgical procedure or open
biopsy

- More than 7 days since prior minor surgical procedure, fine needle aspiration, or
core biopsy (other than bone marrow biopsy)

- No concurrent therapeutic doses of coumadin-derivative anticoagulants (e.g.,
warfarin)

- Doses of ≤ 2 mg daily allowed for prophylaxis of thrombosis

- Prophylactic doses of low molecular weight heparin allowed

- No other concurrent investigational agents for treatment of CLL or SLL

- No other concurrent specific anticancer treatment except hormonal therapy