Pentostatin, Cyclophosphamide, and Rituximab With or Without Bevacizumab in Treating Patients With B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Condition: Leukemia; Lymphoma
MeSH terms: Lymphoma; Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: bevacizumab; pegfilgrastim; rituximab; cyclophosphamide; pentostatin
Intervention description: Given IV; Given subcutaneously; Given IV; Given IV; Given IV
Intervention MeSH terms: Cyclophosphamide; Bevacizumab; Rituximab; Pentostatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 68.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: 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

Summary:

      RATIONALE: Drugs used in chemotherapy, such as pentostatin and cyclophosphamide, work in
      different ways to stop the growth of cancer cells, either by killing the cells or by stopping
      them from dividing. Monoclonal antibodies, such as rituximab and bevacizumab, can block
      cancer growth in different ways. Some block the ability of cancer cells to grow and spread.
      Others find cancer cells and help kill them or carry cancer-killing substances to them. It is
      not yet known whether giving pentostatin and cyclophosphamide together with rituximab is more
      effective with or without bevacizumab in treating patients with B-cell chronic lymphocytic
      leukemia or small lymphocytic lymphoma.

      PURPOSE: This randomized phase II trial is studying the side effects of giving pentostatin
      and cyclophosphamide together with rituximab with or without bevacizumab and to see how well
      it works in treating patients with B-cell chronic lymphocytic leukemia or small lymphocytic
      lymphoma.
    

Eligibility 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:

          -  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