Cyclophosphamide, Fludarabine, Alemtuzumab, and Rituximab (CFAR) for Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)
Condition: Chronic Lymphocytic Leukemia
MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: Fludarabine; Cyclophosphamide; Alemtuzumab; Rituximab
Intervention description: 25 mg/m^2/day IV on Days 3-5; repeated every four weeks for a total of 6 planned cycles.; 250 mg/m^2/day IV on Days 3-5; repeated every four weeks for a total of 6 planned cycles.; 30 mg IV on Days 1, 3 and 5 over 2-4 hours; repeated every four weeks for a total of 6 planned cycles.; Cycle 1 (Week 1): 375 mg/m^2/day IV on Day 2 over 4- 6 hours
Cycle 2 - 6 (Week 1): 500 mg/m^2/day IV on Day 2 over 4- 6 hours
Intervention MeSH terms: Cyclophosphamide; Rituximab; Fludarabine; Fludarabine phosphate; Alemtuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 80.0
Sex: All
Healthy volunteers: No
Keywords: Chronic lymphocytic leukemia; Refractory CLL; CFAR; Alemtuzumab; Campath-1H; Campath; Cyclophosphamide; Cytoxan; Neosar; Fludarabine; Fludara; Fludarabine Phosphate; Rituximab; Rituxan; CLL

Summary:

      The goal of this clinical research study is to learn if the combination of fludarabine,
      cyclophosphamide, alemtuzumab, and rituximab is effective in treating chronic lymphocytic
      leukemia in patients who have already been treated with chemotherapy.

      Primary Objectives:

      Evaluate the therapeutic efficacy, including the complete remission (CR), nodular partial
      remission (NPR), and partial remission (PR) rates (overall response) of combined
      cyclophosphamide, fludarabine, alemtuzumab, and rituximab (CFAR) in previously treated
      patients with Chronic Lymphocytic Leukemia (CLL).

      Second Objectives:

        -  Assess the toxicity profile of CFAR in previously treated patients with CLL.

        -  Monitor for infection and determine incidence and etiology of infection including
           cytomegalovirus in patients treated with CFAR.

        -  Evaluate molecular remission by polymerase chain reaction (PCR) for the clonal
           immunoglobulin heavy chain variable gene in responding patients treated with CFAR.

        -  Assess immune parameters, including pretreatment, during treatment, and post-treatment
           blood T-cell counts and subset distribution and serum immunoglobulin levels in patients
           treated with CFAR.
    

Eligibility criteria:

        Inclusion Criteria:

          1. All patients must have been diagnosed with CLL by immunophenotyping and flow cytometry
             analysis of blood or bone marrow demonstrating a monoclonal population of CD5 and CD19
             positive cells.

          2. All patient must have been previously treated with chemotherapy.

          3. All patients with Rai stage III-IV are eligible for treatment with this protocol. - OR
             - All patients with Rai stage 0-II who meet one or more indication for treatment as
             defined by the NCI-sponsored Working Group are eligible for treatment with this
             protocol.

          4. All patients must have a Zubrod performance status of 0-3.

          5. All patients must have adequate renal and hepatic function (serum creatinine <2mg/dL;
             total bilirubin <2.5mg/dL). Patients with renal or liver dysfunction due to organ
             infiltration by lymphocytes may be eligible after discussion with the Principle
             Investigator and appropriate dose adjustment considered.

          6. Patients may not receive concurrent chemotherapy, radiotherapy, or immunotherapy.
             Localized radiotherapy to an area not compromising bone marrow function does not
             apply, nor do hematopoietic growth factors such as erythropoietin, Granulocyte
             colony-stimulating factor (G-CSF or GCSF, GM-CSF etc).

          7. Patients must not have untreated or uncontrolled life-threatening infection.

          8. Patients must sign informed consent.

        Exclusion Criteria:

        1. None