Bevacizumab in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia
Condition: B-cell Chronic Lymphocytic Leukemia; Refractory Chronic Lymphocytic Leukemia
MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: bevacizumab
Intervention description: Given IV
Intervention MeSH terms: Bevacizumab; Antineoplastic Agents, Immunological; Antibodies; Immunoglobulins; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well bevacizumab works in treating patients with relapsed
      or refractory B-cell chronic lymphocytic leukemia. Monoclonal antibodies, such as
      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. Bevacizumab may also stop the growth of cancer cells by blocking blood
      flow to the cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of B-cell chronic lymphocytic leukemia (CLL)*, as defined by the following
             phenotypic characteristics:

               -  Predominant population of cells share both B-cell antigens (CD19, CD20, or CD23)
                  as well as the T-cell antigen (CD-5), in the absence of other pan-T-cell markers
                  (CD-3, CD-2, etc.)

                    -  Mantle cell lymphoma must be excluded by demonstrating the absence of the
                       t(11;14) by fluorescent in situ hybridization (FISH)

               -  Dim surface immunoglobulin expression

               -  Exclusively kappa and lambda light chains

          -  Peripheral blood absolute lymphocyte count > 5,000/mm^3

               -  Lymphocytosis must consist of small to moderate size lymphocytes, with ≤ 55%
                  prolymphocytes, atypical lymphocytes, or lymphoblasts morphologically

          -  Requires chemotherapy, as indicated by any of the following:

               -  Disease related symptoms, including the following:

                    -  Weight loss ≥ 10% within the previous 6 months

                    -  Extreme fatigue

                    -  Fevers > 100.5°F for 2 weeks without evidence of infection

                    -  Night sweats without evidence of infection

               -  Evidence of progressive marrow failure, as manifested by the development of or
                  worsening anemia (hemoglobin ≤ 10 g/dL) and/or thrombocytopenia (platelet count ≤
                  100,000/mm^3)

               -  Massive (i.e., > 6 cm below left costal margin) or progressive splenomegaly

               -  Measurable and progressive lymphadenopathy

               -  Measurable (i.e., > 5,000/mm^3) and progressive lymphocytosis

          -  Progressive disease or relapsed after or refractory to 1 course of an alkylating
             agent-based or purine nucleoside-based (e.g., fludarabine) regimen

          -  No marrow function attributable to dysplasia related to prior therapy

          -  ECOG performance status 0, 1, or 2

          -  Serum creatinine < 2 mg/dL

               -  If serum creatinine > 1.5 mg/dL but < 2 mg/dL, creatinine clearance must be ≥ 30
                  mL/min

          -  Platelet count > 30,000/mm^3

          -  Direct bilirubin ≤ 2 mg/dL

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  No other second malignancy within the past 2 years except squamous cell or basal cell
             carcinoma of the skin or in situ carcinoma of the cervix

          -  No New York Heart Association class III or IV heart failure

          -  No blood pressure > 150/90 mm Hg

          -  No unstable angina

          -  No myocardial infarction or stroke within the past 6 months

          -  No clinically significant peripheral vascular disease

          -  No evidence of bleeding diathesis or coagulopathy

          -  No significant traumatic injury within the past 28 days

          -  Urine protein:creatinine (UPC) ratio ≤ 1.0

               -  Patients with a UPC ratio > 1.0 must undergo a 23-hour urine collection and must
                  demonstrate < 1 gram of protein per day

          -  No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within
             the past 6 months

          -  No serious, non-healing wound, ulcer, or bone fracture

          -  No active infections requiring oral or intravenous antibiotics

          -  No active bleeding or pathological conditions that carry a high risk of bleeding
             (e.g., known varices)

          -  No thrombocytopenia requiring transfusion

          -  See Disease Characteristics

          -  More than 4 weeks since prior participation in an experimental drug study

          -  At least 8 weeks since prior rituximab

          -  At least 6 weeks since prior chemotherapy

          -  More than 28 days since prior major surgery or open biopsy

          -  More than 7 days since prior minor surgery, fine needle aspirations, or core biopsies

          -  No concurrent major surgery

          -  No concurrent participation in another experimental drug study

          -  Concurrent full-dose warfarin or low molecular weight heparin allowed provided patient
             is on a stable dose AND INR is in range