Trial of Pentostatin Plus Cyclophosphamide With Ofatumumab (PCO) in Older Patients With Chronic Lymphocytic Leukemia

Inclusion Criteria: * Diagnosis of B-CLL defined by: 1. Circulating lymphocytes of more than or equal to 5 x109/L B lymphocytes (5000/mL) in the peripheral blood for the duration of at least 3 months. AND 2. Flow cytometry confirmation of immunophenotype: CD5, CD19, CD20, CD23, CD79b, and surface Ig * Age ≥ 65 years * Active disease and indication for treatment based on modified NCI-WG guidelines defined by presenting at least any one of the following conditions: * Evidence of progressive marrow failure as manifested by development of, or worsening of anemia and/or thrombocytopenia * Massive (i.e. \> 6 cm below the left costal margin) or progressive or symptomatic splenomegaly * Massive nodes (i.e. \> 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy * Progressive lymphocytosis with an increase of \> 50% over a two month period or an lymphocyte doubling time \< 6 months * A minimum of any one of the following disease-related symptoms must be present: 1. Unintentional Weight loss ³ 10% within the previous six months 2. Fevers \> 38.0 °C for ≥ 2 weeks without evidence of infection 3. Night sweats for more than 1 month without evidence of infection * Not been previously treated for B-CLL (prior autoimmune hemolytic anemia treatment permitted) * ECOG Performance Status of 0-2 * Signed written informed consent prior to performing any study-specific procedures Exclusion Criteria: * Prior therapy for B-CLL with any agent except corticosteroids used to treat autoimmune hemolytic anemia * Active autoimmune hemolytic anemia (AIHA) requiring corticosteroid therapy \> 100 mg equivalent to hydrocortisone, or chemotherapy * Known Richter transformation * Known CNS involvement of B-CLL * Any radiation therapy ≤ 4 weeks prior to registration; * Any major surgery ≤ 4 weeks prior to registration; * Chronic or current infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis and active Hepatitis C * Past or current malignancy with the exception of basal cell carcinoma of the skin or in situ carcinoma of the cervix or the breast unless the tumor was successfully treated with curative intend at least 2 years prior to trial entry. * Clinically significant cardiac disease including unstable angina, acute myocardial infarction within 6 months prior to Visit 1, congestive heart failure, and arrhythmia requiring therapy, with the exception of extra systoles or minor conduction abnormalities * History of significant cerebrovascular disease * Glucocorticoid unless given in doses ≤ 100 mg/day hydrocortisone (or equivalent dose of other glucocorticoid) if for exacerbations other than B-CLL (e.g. asthma) * Known HIV positive * Positive serology for Hepatitis B (HB), defined as a positive test for HBsAg. In addition if negative for HBsAg but HBcAb positive and HBsAb negative a HB DNA test will be performed and if positive the subject will be excluded. Note: if HBcAb positive and HBsAb positive, which is indicative of a past infection, the subject can be included. * Screening laboratory values: 1. Creatinine Clearance \< 60 mL/min 2. Total bilirubin \> 2.0 times upper normal limit (unless due to liver involvement of BCLL) 3. ALT \> 3.0 times upper normal limit (unless due to liver involvement of B-CLL) * Treatment with any non-marketed drug substance or experimental therapy within 4 weeks prior to Visit 1 or currently participating in any other interventional clinical study * Known or suspected inability to comply with the study protocol