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

OBJECTIVES:

- To determine the response rate in patients with previously untreated B-cell chronic
lymphocytic leukemia treated with alemtuzumab and rituximab.

- To evaluate the toxicity of alemtuzumab and rituximab in these patients.

OUTLINE: Patients receive alemtuzumab subcutaneously on days 1, 3, and 5 in weeks 1-18 and
rituximab IV on day 1 in weeks 3, 5, 7, 9, 11, 13, 15, and 17 in the absence of disease
progression or unacceptable toxicity.

Peripheral blood and bone marrow samples are collected periodically for laboratory biomarker
studies. Samples are analyzed for surface markers (e.g., CD3, CD4, CD8, CD10, CD19, CD20,
CD25, CD38, CD52, Zap-70) and IgVH by PCR, flow cytometry, and FISH. Samples are also
analyzed for alemtuzumab and anti-alemtuzumab antibody levels by flow cytometry.

After completion of study treatment, patients are followed periodically for 5 years.

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)