Rituximab, Pentostatin, Cyclophosphamide, and Lenalidomide in Treating Patients With Previously Untreated 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: Monoclonal antibodies, such as rituximab, 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. 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. Lenalidomide may stop
      the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving
      rituximab together with combination chemotherapy and lenalidomide may kill more cancer cells.

      PURPOSE: This phase II trial is studying how well giving rituximab together with pentostatin,
      cyclophosphamide, and lenalidomide works in treating patients with previously untreated
      B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  To assess the rate of complete and overall response using pentostatin, cyclophosphamide,
           and rituximab (PCR) followed by consolidation with lenalidomide in patients with
           previously untreated B-cell chronic lymphocytic leukemia (CLL) or small lymphocytic
           lymphoma.

      Secondary

        -  To assess the proportion of patients who convert from a nodular partial response (nPR),
           PR, or stable disease after completing PCR to a complete response (CR) after 6 cycles of
           consolidation with lenalidomide.

        -  To assess the proportion of patients who convert from a CR with detectable minimal
           residual disease (MRD) after PCR to a CR with MRD negative state after 6 courses of
           consolidation with lenalidomide.

        -  To assess the proportion of patients who convert from a CR with detectable MRD, nPR, PR,
           or stable disease with residual disease after PCR to a CR with MRD negative state after
           6 cycles of consolidation with lenalidomide.

        -  To monitor and assess toxicity of this regimen.

        -  To determine if molecular prognostic parameters (e.g., ZAP-70, CD38, cytogenetic
           abnormalities identified by FISH, IgVH mutation status) relate to response to
           PCR-lenalidomide therapy.

        -  To use evaluation of MRD to determine the duration of lenalidomide therapy.

        -  To determine the progression-free survival in CLL patients using this treatment regimen.

      OUTLINE: This is a multicenter study.

        -  Induction therapy: Patients receive rituximab IV over 4 hours on days 1 and 2 of course
           1, and over 1 hour on day 1 of each subsequent course. Patients also receive pentostatin
           IV over 30 minutes and cyclophosphamide IV over 30 minutes on day 1, and pegfilgrastim
           subcutaneously on day 2. Treatment repeats every 21 days for up to 6 courses in the
           absence of disease progression or unacceptable toxicity.

        -  Consolidation therapy: Beginning 2 months after completion of induction therapy,
           patients receive oral lenalidomide once daily on days 1-28. Treatment repeats every 28
           days for 6 courses in the absence of disease progression or unacceptable toxicity.

        -  Continuation therapy: Patients with residual disease continue to receive lenalidomide as
           in consolidation therapy until they achieve a minimal residual disease-negative status
           or complete remission. Patients who achieve complete response with no detectable disease
           discontinue therapy and enter the observation phase.

      Blood samples are collected periodically during treatment for translational and pharmacologic
      studies. Samples are analyzed for immunoglobulin heavy chain gene mutational status, ZAP-70
      status, and levels of VEGF, bFGF, thrombospondin, and TGF-beta by ELISA; and for the effects
      of therapy on immune function. Samples are also stored for future research. Bone marrow
      aspirate samples are analyzed for minimal residual disease by flow cytometry.

      After completion of study treatment, patients are followed every 90 days for 3 years.
    

Intervention name(s): Rituximab; Cyclophosphamide; Lenalidomide; Pentostatin
Intervention type(s): Biological; Drug; Drug; Drug
Intervention description(s): Cycle 1: 100 mg by IV on day 1, 375 mg/m^2 by IV on day 2 Cycle 2-6: 375 mg/m^2 by IV on day 1 (every 21 days); 600 mg/m^2 by IV on day 1 of cycles 1-6 (every 21 days); Cycle 7: 5 mg orally daily on days 1-28 Cycle 8: 10 mg orally daily on days 1-28 as tolerability permits Cycle 9 and beyond: 10 mg orally daily on days 1-28; 2 mg/m^2 by IV on day 1 of cycles 1-6 (every 21 days)
Intervention MeSH terms: Cyclophosphamide; Rituximab; Lenalidomide; Pentostatin
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: B-cell chronic lymphocytic leukemia; stage I chronic lymphocytic leukemia; stage II chronic lymphocytic leukemia; stage III chronic lymphocytic leukemia; stage IV chronic lymphocytic leukemia; contiguous stage II small lymphocytic lymphoma; noncontiguous stage II small lymphocytic lymphoma; stage I small lymphocytic lymphoma; stage III small lymphocytic lymphoma; stage IV small lymphocytic lymphoma