A Phase II Trial of Alemtuzumab and Rituximab in Patients With Previously Untreated CLL
A Phase II Trial of Alemtuzumab and Rituximab in Patients With Previously Untreated CLL
RATIONALE: Monoclonal antibodies, such as alemtuzumab and rituximab, can block cancer growth
 in different ways. Some block the ability of cancer cells to grow and spread. Others find
 cancer cells and help kill them or carry cancer-killing substances to them. Giving
 alemtuzumab together with rituximab may kill more cancer cells.

 PURPOSE: This phase II trial is studying the side effects of giving alemtuzumab together with
 rituximab and to see how well it works in treating patients with previously untreated B-cell
 chronic lymphocytic leukemia.
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)