A Phase II Trial of Alemtuzumab and Rituximab in Patients With Previously Untreated CLL

DISEASE CHARACTERISTICS:

• Diagnosis of B-cell chronic lymphocytic leukemia (CLL)*, as defined by the following criteria:

  • Peripheral blood absolute lymphocyte count > 5,000/mm³
  • Small- to moderate-size lymphocytes with < 55% prolymphocytes, atypical lymphocytes, or lymphoblasts

  • Phenotypically characterized B-CLL expressing CD20 and CD52, as defined by the following:

    • Predominant population of cells share B-cell antigens with CD-5 in the absence of other pan-T-cell markers (e.g., CD-3, CD-2)
    • B-cell expresses either lambda or kappa light chains
    • Surface immunoglobulin with low-cell surface density expression NOTE: *Presence of splenomegaly, hepatomegaly, or lymphadenopathy are not required for the diagnosis of CLL

• Requires therapy, as indicated by ≥ 1 of the following criteria:

  • Unintentional weight loss > 10% within the past 6 months
  • Extreme fatigue (i.e., ECOG performance status 2)
  • Fevers > 100.5°F for 2 weeks without evidence of infection
  • Night sweats without evidence of infection
  • Evidence of progressive marrow failure as manifested by the development of or worsening of anemia (hemoglobin < 10 g/dL) and/or thrombocytopenia (platelet count < 100,000/mm³)
  • Massive (i.e., > 6 cm below left costal margin) or progressive splenomegaly
  • Massive nodes/clusters (> 5 cm), progressive symptomatic adenopathy, or adenopathy resulting in end-organ damage
  • Progressive lymphocytosis with an increase of > 50% over 2 months or an anticipated doubling time < 6 months
• Marked hypogammaglobulinemia or the development of a monoclonal protein in the absence of any of the above criteria for active disease is not sufficient for eligibility

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• ANC ≥ 1,000/mm³*
• Platelet count ≥ 50,000/mm³*
• Hemoglobin ≥ 10 g/dL*
• Serum creatinine ≤ 2.0 mg/dL OR creatinine clearance > 40 mL/min
• Bilirubin < 2 mg/dL
• AST and ALT ≤ 2 times normal (unless secondary to tumor infiltration/lymphadenopathy)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after completion of study treatment
• No active autoimmune anemia or thrombocytopenia
• No active infection requiring oral or intravenous antibiotics
• No second malignancy, other than basal cell carcinoma of the skin or in situ carcinoma of the cervix, unless curatively treated ≥ 2 years ago NOTE: *If cytopenias are due to degree of bone marrow involvement, patient may be eligible at the discretion of the principal investigator.

PRIOR CONCURRENT THERAPY:

• Prior corticosteroid therapy allowed
• No prior cytotoxic therapy (other than corticosteroids)