This is a Phase II, single-arm study of ofatumumab investigating the safety of an accelerated infusion schedule of ofatumumab in patients who have received at least one prior therapy for CLL. The primary endpoint is to evaluate the number of subjects able to complete infusion number 3 (2000 mg) within 15 minutes of the planned time.

The purpose of this study is to develop an accelerated infusion regimen that allows ofatumumab to be delivered in a safe manner while minimizing the time required administering the treatment. We hypothesize there will be fewer infusion-related reactions using the proposed dose-dense approach the first week before accelerating the rate of infusion.

Inclusion Criteria:

1. CD20+ B-cell chronic lymphocytic leukemia (B-CLL) according to International Workshop on CLL Working Group (IWCLL WG) Diagnostic Criteria.

2. Have received at least one prior therapy for CLL.

   •If previously treated with ofatumumab must have achieved at least a partial response (PR) and maintained PR for >= 6 months.

3. Requires treatment according to IWCLL-Working Group guidelines.

4. Eastern Cooperative Oncology Group Performance Status (ECOG PS) <=1.

5. Laboratory parameters <=7 days prior to treatment initiation:

   1. Creatinine <= 1.5 mg/dL upper limit normal (ULN)
   2. Aspartate amino transferase (AST) or alanine amino transferase (ALT) <= 3.0 x ULN
   3. Alkaline phosphatase (ALP) <= 3.0 x ULN
   4. Total Bilirubin level of < 1.5 mg/dL x the institutional ULN unless secondary to Gilbert's disease (or pattern consistent with Gilbert's)

6. Hepatitis B sAg negative and HepB cAb negative. Note: Patients who are HepB sAg negative but are HepB cAb positive (regardless of HepB sAb status) will NOT be allowed.

7. Women of childbearing potential must have a negative serum pregnancy test performed <=72 hours prior to start of treatment. Women of childbearing potential or men with partners of childbearing potential must use effective birth control measures during treatment. If a woman becomes pregnant or suspects she is pregnant while participating in this study, she must agree to inform her treating physician immediately.

8. Accessible for treatment and follow-up.

9. Able to understand the nature of this study, give written informed consent prior to study entry, and comply with study requirements.

10. No prior antibody therapy for CLL within the previous 3 months.

Exclusion Criteria:

1. Previous treatment with ofatumumab that resulted in a Grade 3 or 4 infusion reaction.
2. Treatment for CLL within last 4 weeks. (Patients who have received steroids or IVIG for autoimmune complications of CLL are eligible).
3. Current active hepatic or biliary disease (with the exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver disease, per assessment by the treating physician).
4. Active bacterial or viral infection or infection requiring intravenous antibiotic treatment at the time of accrual.
5. Central nervous system lymphoma/CLL.
6. Transformation of CLL to aggressive non-Hodgkin lymphoma (NHL) (i.e., Richter's transformation).
7. History of other malignancy <= 2 years of study entry which could affect compliance with the protocol or interpretation of results. History of curatively treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix, low grade, early-stage, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ (DCIS) of the breast treated with curative intent, are generally eligible.
8. Active hepatitis B or C or known HIV positive.
9. Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half lives or 4 weeks prior to visit 1, whichever is longer.
10. History of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelae.
11. Clinically significant cardiac disease including unstable angina, acute myocardial infarction (within 6 months of enrollment), congestive heart failure (NYHA III-IV), and arrhythmia unless controlled by therapy, with the exception of extra systoles or minor conduction abnormalities.
12. Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease which in the opinion of the investigator may represent a risk for the patient.

For 28 weeks during treatment then every 3 months for 2 years, and every 6 months thereafter until disease progression.

All patients who received at least one dose of protocol treatment are included in the safety analysis.