Early Treatment of High Risk Chronic Lymphocytic Leukemia With Alemtuzumab, Rituximab, and PGG Beta-Glucan: A Phase I/II Trial

Inclusion Criteria:

- Diagnosis of CLL (Hallek, Cheson et al. 2008) manifested by: Minimum threshold
peripheral lymphocyte count of 5 x 10^9/L AND immunophenotypic demonstrations of a
population of B lymphocytes (as defined by CD19+) which are monoclonal (light chain
exclusion); CLL will be diagnosed if these cells have >= 3 of the following
characteristics: CD5+, CD23+, dim surface light chain expression, dim surface CD20
expression AND fluorescence in situ hybridization (FISH) analysis is negative for
IGH/CCND1 and/or immunostaining is negative for cyclin D1 expression

- >= 1 of the following poor prognosis factors: unmutated IGHV (< 2%) AND CD38
expression (>= 30% cells positive on flow cytometry); unmutated IGHV (< 2%) AND
ZAP-70 expression (>= 20% cells positive on flow cytometry); use of VH3-21 gene
segment irrespective of mutation status AND CD38 expression (>= 30% cells positive on
flow cytometry); use of VH3-21 gene segment irrespective of mutation status AND
ZAP-70 expression (>= 20% cells positive on flow cytometry); 11q22-; 17p13-

- Rai classification Stage 0, I or II that does not meet standard NCI-IWCLL criteria
for treatment of CLL (Hallek, Cheson et al. 2008)

- Limited CLL disease burden with no lymph nodes > 5 cm in any diameter and
splenomegaly < 6 cm below left costal margin in midclavicular line at rest

- Creatinine =< 1.5 x upper normal limit (UNL)

- Total bilirubin =< 3.0 x UNL; if total is elevated, a direct bilirubin should be
performed and should be =< 1.5 x UNL

- AST =< 3.0 x UNL

- Eastern Cooperative Oncology Group (ECOG) performance status (PS): 0, 1, or 2

- Negative serum pregnancy test done =< 7 days prior to registration, for women of
childbearing potential only

- Provide informed written consent

- Willing to return to a Lymphoma Specialized Program of Research Excellence (SPORE)
enrolling institution for follow-up

- Willing to provide blood samples for correlative research purposes

Exclusion Criteria:

- Pregnant women

- Nursing women

- Men or women of childbearing potential who are unwilling to employ adequate
contraception

- New York Heart Association Class III or IV heart disease

- Recent myocardial infarction (< 1 month)

- Uncontrolled infection

- Infection with the human immunodeficiency virus/acquired immune deficiency syndrome
(HIV/AIDS), serological evidence of active hepatitis B infection (HBsAg or HBeAg
positive) or positive hepatitis C serology, as further severe immunosuppression with
this regimen may occur

- Evidence of active autoimmune hemolytic anemia, immune thrombocytopenia, or pure red
blood cell aplasia

- Other active primary malignancy requiring treatment or limits survival to =< 2 years

- Any major surgery =< 4 weeks prior to registration

- Any previous chemotherapy or monoclonal antibody treatment for CLL

- Current use of corticosteroids; NOTE: previous corticosteroids are allowed