Pentostatin, Cyclophosphamide, and Rituximab With or Without Bevacizumab in Treating Patients With B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

This is an interventional treatment trial for Leukemia focused on measuring B-cell chronic lymphocytic leukemia, stage 0 chronic lymphocytic leukemia, stage I chronic lymphocytic leukemia, stage II chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia, stage I small lymphocytic lymphoma, stage III small lymphocytic lymphoma, stage IV small lymphocytic lymphoma, contiguous stage II small lymphocytic lymphoma, noncontiguous stage II small lymphocytic lymphoma Read More

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:

• Eastern Cooperative Oncology Group 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)
• Serum glutamate oxaloacetate transaminase ≤ 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