PH2 Trial in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL) With a Combination of Bendamustine & Ofatumumab

PHASE II CLINICAL PROTOCOL FOR THE TREATMENT OF PATIENTS WITH RELAPSED/REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA WITH A COMBINATION OF BENDAMUSTINE AND OFATUMUMAB

Investigational Drugs:

Ofatumumab (Azerra) + bendamustine (Trenda)

Route of Administration:

Intravenous (IV)

Hypothesis:

This study is designed to assess the toxicity and overall response rate. Ofatumumab is a fully human monoclonal antibody (A type of protein made in the laboratory that can bind to substances in the body, including tumor cells) that shows promising activity in the treatment of CLL as a single agent. It is thought that by combining it with Bendamustine, an FDA approved treatment for CLL, the effect on CLL will be greater than if Ofatumumab is given alone. Ofatumumab is FDA approved for the treatment of relapsed/refractory CLL.

Participation:

Approximately 37 relapsed/refractory CLL subjects will participate in this study over two years.

Treatment Plan:

A maximum of 6 cycles of treatment will be allowed. During day 1 of cycle 1 ofatumumab IV 300mg will be administered. On day 1 of all cycles ofatumumab treatment will be followed by bendamustine IV 90mg/m2. On day 2 of all cycles, bendamustine IV 90mg/m2 will be administered. On day 3 of all cycles, neulasta SQ 6mg will be given. On day 8 of cycle 1 only patients will receive ofatumumab IV 1000mg. During cycles 2 through 6 ofatumumab 1000mg will be given on day 1 only.

Follow-up:

Patients will be followed monthly for six months, then every three months for five years then annually thereafter.

Inclusion Criteria:

• Must be >/= 18 years old and able to provide consent
• Must have diagnosis of CLL as defined by NCI criteria
• Must require chemotherapy
• Must be previously treated with a minimum of one course of prior chemo or other treatment
• Serum creatinine <1.8 mg/dl
• Bilirubin must be </= 2 mg/d, unless secondary to tumor
• Must have adequate liver function (as defined as <2x ULN, unless related to CLL)
• AST/ALT <2x ULN
• Performance status 0-2
• Women of child bearing age must be willing to use accepted/effective method of birth control.

Exclusion Criteria:

• Not have received prior treatment with cytotoxic chemotherapy or immunotherapy.
• Not have autoimmune hemolytic anemia or autoimmune thrombocytopenia
• Not have history of corticosteroid treatment for CLL
• Not have CNS disease
• Not have clinically significant infections
• Patients with a second malignancy, other than basal cell carcinoma of the skin or in situ carcinoma of the cervix are not eligible.
• Not have positive serology for Hepatitis B or Hepatitis C
• Not have be known to be HIV positive
• Not have New York Classification III or IV hear disease

Other protocol specific criteria may apply