Fludarabine, Rituximab, and Alemtuzumab in Treating Patients With Chronic Lymphocytic Leukemia
Condition: 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
MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: alemtuzumab; rituximab; fludarabine phosphate
Intervention description: Given SC; Given IV; Given IV
Intervention MeSH terms: Rituximab; Antineoplastic Agents, Immunological; Alemtuzumab; Fludarabine; Fludarabine phosphate; Antibodies; Immunoglobulins; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 102.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well giving fludarabine together with rituximab followed
      by alemtuzumab works in treating patients with chronic lymphocytic leukemia. 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 can find cancer cells and
      help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such
      as fludarabine, work in different ways to stop the growth of cancer cells, either by killing
      the cells or by stopping them from dividing. Giving fludarabine together with rituximab
      followed by alemtuzumab may kill more cancer cells.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Specific Diagnosis of B-Cell CLL

          -  An absolute lymphocytosis of > 5,000/μL

          -  Morphologically, the lymphocytes must appear mature with < 55% prolymphocytes

          -  Bone marrow examination must include at least a unilateral aspirate and biopsy; the
             aspirate smear must show > 30% of all nucleated cells to be lymphoid or the bone
             marrow core biopsy must show lymphoid infiltrates compatible with marrow involvement
             by CLL; the overall cellularity must be normocellular or hypercellular

          -  Local institution lymphocyte phenotype must reveal a predominant B-cell monoclonal
             population sharing a B-cell marker (CD19, CD20, CD23) with the CD5 antigen, in the
             absence of other pan-T-cell markers; additionally, the B-cells must be monoclonal with
             regard to expression of either κ or λ and have surface immunoglobulin expression of
             low density; patients with bright surface immunoglobulin levels must have CD23
             co-expression

          -  Patients must be in the intermediate- or high-risk categories of the modified
             three-stage Rai staging system (i.e., stages I, II, III, or IV)

          -  Patients in the intermediate-risk group must have evidence of active disease as
             demonstrated by at least one of the following criteria:

               -  Massive or progressive splenomegaly, hepatomegaly and/or lymphadenopathy;

               -  Presence of weight loss > 10% over the preceding 6 month period;

               -  Grade 2 or 3 fatigue;

               -  Fevers > 100.5°F or night sweats for greater than 2 weeks without evidence of
                  infection;

               -  Progressive lymphocytosis with an increase of > 50% over a 2 month period or an
                  anticipated doubling time of less than 6 months

          -  No prior therapy for CLL including corticosteroids for autoimmune complications that
             have developed since the initial diagnosis of CLL

          -  No medical condition requiring chronic use of oral corticosteroids

          -  Performance Status 0 - 2

          -  Due to alterations in host immunity, patients with HIV may not be enrolled

          -  Due to the unknown teratogenic potential of alemtuzumab, pregnant or nursing women may
             not be enrolled; women and men of reproductive potential should agree to use an
             effective means of birth control

          -  Creatinine =< 1.5 x upper limit of institutional normal value

          -  Coomb's Testing NEGATIVE