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
Intervention: Rituximab; Cyclophosphamide; Lenalidomide; Pentostatin
Intervention description: 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
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 45.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
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

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.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL),
             meeting the following criteria:

               -  Biopsy-proven SLL according to WHO criteria

               -  CLL diagnosis* according to NCI working group criteria as evidenced by all of the
                  following:

                    -  Peripheral blood lymphocyte count of > 5,000/mm³

                    -  Small to moderate peripheral blood lymphocyte with < 55% prolymphocytes

                    -  Immunophenotyping consistent with CLL defined as:

                         -  B-cell markers with CD5 antigen in the absence of other pan-T-cell
                            markers (e.g., CD3, CD2)

                         -  CD19, CD20, or CD23

                         -  Dim surface immunoglobulin expression

                         -  Exclusively kappa or lambda light chains

                    -  Diagnosis of mantle cell lymphoma must be excluded by negative FISH analysis
                       for t(11;14)(IgH/CCND1) on peripheral blood or tissue biopsy or negative
                       immunohistochemical stains for cyclin D1 on involved tissue biopsy NOTE:
                       *Splenomegaly, hepatomegaly, or lymphadenopathy are not required for the
                       diagnosis of CLL

          -  Previously untreated disease and meets ≥ 1 of the following criteria*:

               -  At least 1 or more of the following disease-related symptoms:

                    -  Weight loss > 10% within the previous 6 months

                    -  Extreme fatigue attributed to CLL

                    -  Fevers > 100.5º 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 (i.e., hemoglobin ≤ 11 g/dL) and/or thrombocytopenia (i.e.,
                  platelet count ≤ 100,000/mm³) not due to autoimmune disease

               -  Symptomatic or progressive lymphadenopathy, splenomegaly, or hepatomegaly

               -  Progressive lymphocytosis due to CLL with an increase of > 50% over a 2-month
                  period or an anticipated doubling time < 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 for protocol
                  therapy

        PATIENT CHARACTERISTICS:

          -  ECOG performance status 0-3

          -  Serum creatinine ≤ 1.5 times upper limit of normal (ULN)

          -  Total bilirubin ≤ 3.0 times ULN (unless due to Gilbert disease)

               -  Direct bilirubin < 1.5 mg/dL for Gilbert disease to be diagnosed if total
                  bilirubin > 3.0 times ULN

          -  AST and ALT ≤ 3.0 times ULN (unless due to hemolysis or CLL)

          -  Willing to provide blood samples

          -  Able to take acetylsalicylic acid (ASA) (81 or 325 mg) daily as prophylactic
             anticoagulation (patients intolerant to ASA may use low molecular weight heparin)

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Female patients must use effective double-method contraception beginning 1 month prior
             to, during, and for 4 weeks after completion of study treatment

          -  Male patients must use effective contraception during and for 4 weeks after completion
             of study treatment

          -  No comorbid conditions, including any of the following:

               -  New York Heart Association class III or IV heart disease

               -  Recent myocardial infarction (< 1 month)

               -  Uncontrolled infection

               -  Infection with HIV/AIDS

          -  No other active primary malignancy requiring treatment or that limits survival to ≤ 2
             years

          -  No history of deep venous thrombosis or pulmonary embolism ≤ 12 months prior to study
             registration

          -  No active hemolytic anemia requiring immunosuppressive or other pharmacologic therapy

        PRIOR CONCURRENT THERAPY:

          -  See Disease Characteristics

          -  No prior chemotherapy or monoclonal antibody-based therapy for treatment of CLL

          -  Nutraceutical treatments with no established benefit in CLL (e.g., epigallocatechin
             gallate or other herbal treatments) are not considered prior therapy

          -  More than 4 weeks since prior radiotherapy

          -  At least 4 weeks since prior major surgery

          -  No concurrent corticosteroids

               -  Concurrent low doses of steroids (e.g., < 10 mg of prednisone or equivalent dose
                  of other steroid) used for treatment of non-hematologic medical conditions
                  allowed

               -  Prior use of corticosteroids allowed

          -  No prior thalidomide or lenalidomide

          -  No concurrent therapeutic doses of coumadin-derivative anticoagulants (e.g., warfarin)

               -  Doses of ≤ 2 mg daily allowed for thrombosis prophylaxis

               -  Prophylactic doses of low molecular weight heparin allowed