CFAR Study in Patients With Chronic Lymphocytic Leukemia
Condition: Leukemia; Chronic Lymphocytic Leukemia
MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: Cyclophosphamide; Fludarabine; Alemtuzumab; Rituximab
Intervention description: 200 mg/m^2/day 3-5 IV 5-30 minutes; 20 mg/m^2/day 3-5 IV 5-30 minutes; 30 mg Days 1, 3, 5 IV 2-4 hours; 375 mg/m^2/day 2 IV 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: 60.0
Sex: All
Maximum age: 69 Years
Healthy volunteers: No
Keywords: Chronic Lymphocytic Leukemia; CML; Leukemia; Cyclophosphamide; Fludarabine; Alemtuzumab; Rituximab; CFAR

Summary:

      Primary Objective:

      1. Evaluate the ability of Cyclophosphamide, Fludarabine, Alemtuzumab, and Rituximab (CFAR)
      to increase the proportion of patients with <5% CD5/CD19+ cells in bone marrow to 66%
      following 3 courses of treatment without significantly increasing the incidence of pneumonia
      or sepsis compared to a historic group of patients treated with the combination fludarabine,
      cyclophosphamide, and rituximab (FCR).

      Second Objectives:

        1. Assess complete remission (CR), nodular partial remission (nPR), and partial remission
           (PR) rates (overall response) in high-risk, previously untreated patients with CLL
           treated with CFAR.

        2. Evaluate molecular remission in bone marrow by polymerase chain reaction (PCR) for the
           clonal immunoglobulin heavy chain variable gene in responders treated with CFAR.

        3. Assess immune parameters including blood T cell counts and subset distribution and serum
           immunoglobulin levels pretreatment, during treatment, and post-treatment in patients
           treated with CFAR.
    

Eligibility criteria:

        Inclusion Criteria:

          -  All patients must have a diagnosis of CLL by immunophenotyping and flow cytometry
             analysis of blood or bone marrow and be previously untreated.

          -  All patients must be younger than 70 years and have a serum beta-2 microglobulin of
             >/= 4.0mg/L.

          -  All patients with Rai stage III-IV are eligible for treatment on 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 on this
             protocol.

          -  All patients must have a Zubrod performance status of 0-3.

          -  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.

          -  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), Granulocyte-Macrophage Colony Stimulating Factor
             (GM-CSF), etc.

          -  Patients must not have untreated or uncontrolled life-threatening infection.

          -  Patients must sign informed consent.

        Exclusion Criteria:

        Patients older than 70 years.