Rituximab, Alemtuzumab, and GM-CSF As First-Line Therapy in Treating Patients With Early-Stage Chronic Lymphocytic Leukemia
Condition: Leukemia
MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: Alemtuzumab; Rituximab; Sargramostim
Intervention description: Week 1 (dose escalation):
Day 3: 3mg subcutaneously; Day 4: 10mg subcutaneously; Day 5 30mg subcutaneously
Weeks 2-5:
30mg subcutaneously three times a week.; Weeks 2-5:
375 mg/m^2 by IV once weekly; Week 1-6:
250 mcg subcutaneously three time as week
Intervention MeSH terms: Rituximab; Alemtuzumab; Sargramostim
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 33.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: stage 0 chronic lymphocytic leukemia; stage I chronic lymphocytic leukemia; stage II chronic lymphocytic leukemia

Summary:

      RATIONALE: Monoclonal antibodies, such as rituximab and alemtuzumab, 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.
      Colony-stimulating factors, such as GM-CSF, may increase the number of immune cells found in
      bone marrow or peripheral blood. Giving monoclonal antibody therapy together with GM-CSF may
      be an effective treatment for early-stage chronic lymphocytic leukemia.

      PURPOSE: This phase II trial is studying the side effects of giving rituximab and alemtuzumab
      together with GM-CSF and to see how well it works in treating patients with early-stage
      chronic lymphocytic leukemia.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Diagnosis of chronic lymphocytic leukemia (CLL) meeting the following criteria:

               -  Minimum threshold peripheral blood lymphocyte count 5 x 10^9/L

               -  Monoclonality (light chain exclusion) of B lymphocytes detected by
                  immunophenotyping (CD19-positive), demonstrating ≥ 3 of the following
                  characteristics:

                    -  CD5-positive

                    -  CD23-positive

                    -  Dim surface light chain expression

                    -  Dim surface CD20 expression

               -  Negative for IGH/CCND1 translocation AND/OR immunostaining is negative for cyclin
                  D1 expression by fluorescent in-situ hybridization (FISH) analysis

               -  Rai stage 0, I, or II disease that does not meet standard NCI-Working Group
                  criteria for treatment of CLL

          -  Poor prognosis as defined by ≥ 1 of the following factors:

               -  Unmutated IgVH mutation status AND CD38 expression (i.e., ≥ 30% cells positive on
                  flow cytometry)

               -  Unmutated IgVH mutation status AND ZAP-70 expression (i.e., ≥ 20% cells positive
                  on flow cytometry)

               -  VH3-21 gene segment use irrespective of mutation status AND CD38 expression (≥
                  30% cells positive on flow cytometry)

               -  VH3-21 gene segment use irrespective of mutation status AND ZAP-70 expression (≥
                  20% cells positive on flow cytometry)

               -  11q-negative*

               -  17p-negative* NOTE: *Determination of IgVH mutation status is not required in
                  patients whose eligibility is based on 17p13- or 11q22- deletions

        PATIENT CHARACTERISTICS:

          -  ECOG performance status 0- 2

          -  Creatinine ≤ 1.5 times upper limit of normal (ULN)

          -  Total bilirubin ≤ 3.0 times ULN OR direct bilirubin ≤ 1.5 ULN

          -  AST ≤ 3.0 times ULN (unless due to hemolysis or CLL)

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must practice effective contraception

          -  Willing to provide mandatory blood samples (for patients at the Mayo Clinic in
             Rochester only) for research studies as required by the protocol

          -  No comorbid conditions, including any of the following:

               -  New York Heart Association Class III or IV heart disease

               -  Myocardial infarction within the past month

               -  Uncontrolled infection

               -  HIV infection or AIDS

               -  Serological evidence of active hepatitis B infection (i.e., serum antigen or
                  e-antigen positivity) or positive hepatitis C serology

          -  No other active primary malignancy requiring treatment or limiting survival to ≤ 2
             years

          -  No active autoimmune hemolytic anemia, immune thrombocytopenia, or pure red blood cell
             aplasia

        PRIOR CONCURRENT THERAPY:

          -  More than 4 weeks since prior major surgery

          -  No prior chemotherapy or monoclonal antibody treatment for CLL

          -  No concurrent corticosteroids