Ofatumumab and High-dose Methylprednisolone in Patients With Chronic Lymphocytic Leukemia (CLL)

Inclusion Criteria

• Previously treated patients with a diagnosis of CLL
• Previous treatment with any monoclonal antibody or chemotherapy regardless of response as defined by the iwCLL Working Group Guidelines as evidenced by:
• progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia
• massive (i.e. at least 6cm below the left costal margin) or progressive or symptomatic splenomegaly
• massive nodes (i.e. at least 10cm in longest diameter) or progressive or symptomatic lymphadenopathy.
• progressive lymphocytosis with an increase of more than 50% over a 2-month period or lymphocyte doubling time (LDT) of less than 6 months.
• autoimmune anemia and/or thrombocytopenia that is poorly responsive to corticosteroids or other standard therapy (See Section 10.2)
• Constitutional symptoms, defined as any one or more of the following disease-related symptoms or signs: unintentional weight loss of 10% or more within the previous 6 months significant fatigue (i.e. ECOG PS 2 or worse, inability to work or perform usual activities), fevers higher than 100.5ºF or 38.0ºC for 2 or more weeks without other evidence of infection, night sweats for more than 1 month without evidence of infection
• Subjects must be 18 years of age or older, male or female.
• ECOG performance status of 0-2.
• Subjects must be able to give informed consent.
• Females of child bearing potential(FCBP)† must have a negative serum or urine pregnancy test within 10 - 14 days prior to and again within 24 hours of starting treatment and agree to use a medically accepted contraceptive method for the duration of this study.

Exclusion Criteria

• Hepatitis BsAg positive, Hepatitis BcAb positive, and Hepatitis C positive patients.
• Known HIV positive patients.
• Diabetics.
• Patients with uncontrolled Autoimmune Hemolytic Anemia (AIHA) or autoimmune thrombocytopenia (ITP).
• Screening laboratory values within these ranges: platelets 2.0 times upper normal limit,total bilirubin >1.5 times upper normal limit (unless a known history of Gilbert's disease), ALT >2.5 times upper normal limit (unless due to disease involvement of liver), alkaline phosphatase >2.5 times upper normal limit (unless due to disease involvement of the liver or bone marrow)
• Inability to provide informed consent.
• Concurrent malignancy (excluding basal and squamous cell skin cancers).
• Active fungal, bacterial, and/or viral infection.
• History of peptic ulcer disease resulting in GI bleeding within the last 6 months.
• Untreated metabolic disorders such as hypothyroidism and Cushing's disease.
• History of steroid-induced psychosis.
• Estimated life expectancy of less than 3 months by the investigator's best clinical judgment.
• Serious medical condition that would render the subject medically unstable.
• Women who are pregnant or breast-feeding.
• History of Pancreatitis.
• History of Diverticulitis.
• Patients with known hypersensitivity to ofatumumab or known history of anaphylaxis to Rituximab or alemtuzumab.
• Concurrent use of other anti-cancer agents or treatments.
• Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment).