Ofatumumab, Pentostatin, and Cyclophosphamide in Treating Patients With Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Inclusion Criteria:

Diagnosis of CLL according to the National Cancer Institute (NCI) criteria or SLL according to the World Health Organization (WHO) criteria, including previous documentation of:
Biopsy-proven SLL

Diagnosis of CLL according to NCI working group criteria as evidenced by all of the following:

Peripheral blood lymphocyte count of > 5,000/mm^3 consisting of small to moderate size lymphocytes, with < 55% prolymphocytes

Immunophenotyping consistent with CLL defined as:

The predominant population of lymphocytes share both B-cell antigens (CD19, CD20 [typically dim expression], or CD23) as well as CD5 in the absence of other pan-T-cell markers (CD3, CD2, etc.)
Clonality as evidenced by kappa or lambda light chain expression (typically dim immunoglobulin expression)
Note: splenomegaly, hepatomegaly, or lymphadenopathy are not required for the diagnosis of CLL
Before diagnosing CLL or SLL, mantle cell lymphoma must be excluded by demonstrating a negative FISH analysis for t(11;14)(immunoglobulin heavy [IgH]/cyclin D1 [CCND1]) on peripheral blood or tissue biopsy or negative immunohistochemical stains for CCND1 on involved tissue biopsy

Patients must be previously untreated and meet at least one of the following indications for chemotherapy:

Evidence of progressive marrow failure as manifested by the development of or worsening anemia (=< 11 g/dl) and/or thrombocytopenia (=< 100,000/mm^3) not due to autoimmune disease
Symptomatic or progressive lymphadenopathy, splenomegaly or hepatomegaly

One or more of the following disease-related symptoms:

Weight loss > 10% within the previous 6 months
Extreme fatigue attributed to CLL
Fevers > 100.5 degree Fahrenheit for 2 weeks without evidence of infection
Drenching night sweats without evidence of infection

Progressive lymphocytosis due to CLL with an increase of > 50% over a two-month period or an anticipated doubling time of less than six months

Prior chemotherapy or monoclonal antibody based therapy for treatment of CLL will be considered prior therapy; nutraceutical treatments with no established benefit in CLL (such as epigallocatechin gallate [EGCG], found in green tea or other herbal treatments) will not be considered "prior treatment"
Marked hypogammaglobulinemia or the development of a monoclonal protein in the absence of any of the above criteria for active disease are not sufficient for protocol therapy
Serum creatinine =< 1.5 x upper normal levels (UNL)
Total bilirubin =< 1.5 x UNL unless due to Gilbert's disease; if total bilirubin is > 1.5 x UNL, a direct bilirubin should be performed and must be < 1.5 mg/dL for Gilbert's to be diagnosed
Aspartate aminotransferase (AST) =< 3.0 x UNL and alanine aminotransferase (ALT) =< 3.0 x UNL (unless due to hemolysis or CLL)
Eastern Cooperative Oncology Group (ECOG) performance status (PS): 0, 1, or 2
Willingness to provide blood samples as required
Able to adhere to the study visit schedule and other protocol requirements

Exclusion Criteria:

Any of the following comorbid conditions:

New York Heart Association Class III or IV heart disease
Recent myocardial infarction (< 1 month)
Uncontrolled infection
Infection with the human immunodeficiency virus (HIV/acquired immunodeficiency syndrome [AIDS])
Infection with known chronic, active Hepatitis C
Positive serology for hepatitis B (HB) defined as a positive test for HB surface antigen (HBsAg); in addition, if negative for HBsAg but HB core antibody (HBcAb) positive (regardless of HBsAb status), a HB deoxyribonucleic acid (DNA) test will be performed and if positive the subject will be excluded
Pregnant women
Nursing women
Men or women of childbearing potential who are unwilling to employ adequate contraception
Other active primary malignancy requiring treatment or limiting survival to =< 2 years
Any radiation therapy =< 4 weeks prior to registration
Any major surgery =< 4 weeks prior to registration
Current use of corticosteroids; EXCEPTION: low doses of steroids (< 10 mg of prednisone or equivalent dose of other steroid) used for treatment of non-hematologic medical conditions; Note: previous use of corticosteroids is allowed
Active hemolytic anemia requiring immunosuppressive therapy or other pharmacologic treatment; patients who have a positive Coombs test but no evidence of hemolysis are NOT excluded from participation