Rapid Infusion of Ofatumumab in Patients With Previously Treated Chronic Lymphocytic Leukemia, a Phase II Trial
1. CD20+ B-cell chronic lymphocytic leukemia (B-CLL) according to International Workshop
on CLL Working Group (IWCLL WG) Diagnostic Criteria (see Appendix A).
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 (Appendix B).
4. Eastern Cooperative Oncology Group Performance Status (ECOG PS) =1 (Appendix D).
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
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
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
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.
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
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
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