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
Study type: Interventional
Phase: Phase 2

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.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  To assess the rate of complete and overall response in patients with B-cell chronic
           lymphocytic leukemia or small lymphocytic lymphoma treated with pentostatin,
           cyclophosphamide, and rituximab with or without bevacizumab.

        -  To assess the proportion of patients who achieve a negative minimal residual disease
           state after treatment with these regimens.

        -  To monitor and assess the adverse events of these regimens.

      Secondary

        -  To determine if molecular prognostic parameters (ZAP-70, CD38, cytogenetic abnormalities
           identified by FISH, and IgVH mutation status) relate to response in these patients.

        -  To determine the progression-free survival of patients treated with these regimens.

        -  To complete additional correlative studies to gain insight into disease biology and how
           it influences drug sensitivity.

      OUTLINE: Patients are stratified according to Rai risk group (high [Rai stage III or IV] vs
      low [Rai stage 0] or intermediate [Rai stage I or II]) and FISH prognosis group (favorable
      [normal, +12, 13q-, or other] vs unfavorable [17p- or 11q-]). Patients are randomized to 1 of
      2 treatment arms.

        -  Arm I: Patients receive bevacizumab IV over 30-90 minutes on day 1 of courses 1-5 and on
           days 1, 22, and 43 of course 6; rituximab IV over 2-4 hours on days 2 and 3 of course 1
           and on day 1 of courses 2-6; and pentostatin IV over 30 minutes and cyclophosphamide IV
           over 30 minutes on day 2 of course 1 and on day 1 of courses 2-6. Patients also receive
           pegfilgrastim subcutaneously (SC) on day 3 of course 1 and on day 2 of courses 2-6.
           Treatment repeats every 21 days* for 6 courses in the absence of disease progression or
           unacceptable toxicity.

      NOTE: *Course 6 is 56 days in duration

        -  Arm II: Patients receive rituximab IV over 2-4 hours on days 1 and 2 of course 1 and on
           day 1 of courses 2-6 and pentostatin IV over 30 minutes and cyclophosphamide IV over 30
           minutes on day 1. Patients also receive pegfilgrastim SC on day 2. Treatment repeats
           every 21 days* for 6 courses in the absence of disease progression or unacceptable
           toxicity.

      NOTE: *Course 6 is 56 days in duration

      Patients undergo blood sample collection and bone marrow biopsy/aspiration periodically for
      translational research studies. Samples are analyzed by flow cytometry for assessment of
      minimal residual disease. Molecular prognostic markers (including CD38, ZAP-70, IgVH gene
      mutation status, and cytogenetic abnormalities by FISH), Tcl-1 and CD49d protein expression,
      and immunoglobulin heavy chain D and J family gene usage are also analyzed. Plasma samples
      are stored for future studies evaluating levels of VEGF, bFGF, and thrombospondin by ELISA.

      After completion of study therapy, patients are followed periodically for up to 5 years.
    

Intervention name(s): bevacizumab; pegfilgrastim; rituximab; cyclophosphamide; pentostatin
Intervention type(s): Biological; Biological; Biological; Drug; Drug
Intervention description(s): Given IV; Given subcutaneously; Given IV; Given IV; Given IV
Other intervention name(s): Avastin
Intervention MeSH terms: Cyclophosphamide; Bevacizumab; Rituximab; Pentostatin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
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