Phase II Fludarabine, Cytoxan and FCCAM in Untreated B-Cell Chronic Lymphocytic Leukemia

Inclusion Criteria:

• Male or female, age 18 or older, with a confirmed immunohistological diagnosis of CLL
• Signed written informed consent
• Karnofsky performance status 60% or above (Appendix E)
• Advanced stage disease (Rai Stage III or IV, or modified Rai High Risk).

• Patients with Rai Stage I - II or (Modified Rai Intermediate-Risk) disease must have an indication for therapy based on 1996 NCI revised criteria for active disease as follows:

  • Any one of the following disease-related symptoms:

    1. Weight loss >= 10% within the previous 6 months
    2. Extreme fatigue
    3. Fever greater than 100.5° F for >= 2 weeks without evidence of infection
    4. Night sweats without evidence of infection
  • Evidence of progressive marrow failure based on the development of worsening of anemia or thrombocytopenia
  • Autoimmune anemia and/or thrombocytopenia poorly responsive to corticosteroid therapy
  • Massive (> 6 cm below the left costal margin) or progressive splenomegaly
  • Bulky (>10 cm in cluster) or progressive lymphadenopathy
  • Progressive lymphocytosis > 50% increase over 2 months, or anticipated doubling time < 6 months
• Patients with immunoglobulin VH gene in unmutated nucleotide sequence configuration, as defined by >= 98% homology with the nearest germline counterpart, regardless of Rai Stage.
• Serum creatinine <= 2x the upper limit of normal. Total serum bilirubin, AST, and ALT: <= 2x the upper limit of normal.

Exclusion Criteria:

• Prior pharmacological treatment for CLL.
• Any medical condition requiring systemic corticosteroids.
• Active systemic infection.
• HIV positive by serologic testing.
• Past history of anaphylaxis following exposure to monoclonal antibodies.
• Active secondary malignancy or a history of malignant disease (other than CLL or non-melanoma skin cancer) within the preceding 5 years.
• Pregnant or nursing women, or unwilling/unable to practice an acceptable form of contraception. Treatment with the study agents would expose an unborn child to significant risks.
• Major systemic or other illness (including Coombs positivity and active hemolysis) that would, in the opinion of the investigator, interfere with the patient's ability to comply with the protocol, compromise patient safety, or interfere with the interpretation of study results.