Safety and Efficacy Study of TRU-016 Plus Bendamustine vs. Bendamustine in Relapsed Chronic Lymphocytic Leukemia

A Phase 1b/2 Open Label Study to Evaluate the Safety and Efficacy of TRU-016 in Combination With Bendamustine vs. Bendamustine Alone in Patients With Relapsed Chronic Lymphocytic Leukemia

The objective of the first part of the study is to determine a safe dose of TRU-016 that can be used in combination with bendamustine in patients with relapsed CLL. The objectives of the second part of the study are to compare the safety and efficacy of TRU-016 in combination with bendamustine to bendamustine alone in patients with relapsed CLL.

This study consisted of two parts. The initial dose escalation stage was a Phase 1b study evaluating the safety and tolerability of two doses of TRU-016 administered in combination with bendamustine to patients with relapsed chronic lymphocytic leukemia (CLL). In the randomized Phase 2 stage of the study, the efficacy and safety of the selected dose of 20 mg/kg TRU-016 combined with bendamustine was compared to bendamustine alone. The pharmacokinetics and pharmacodynamics of TRU-016 and the development of antibodies to TRU-016 were evaluated in both phases of the study.

Inclusion Criteria:

• Diagnosis of relapsed CLL with 1 to 3 prior treatments
• Demonstrated active disease requiring treatment
• No prior bendamustine treatment
• Not refractory to fludarabine or other purines, either as a single agent or in combination
• Age >/=18 years; male or female
• Eastern Cooperative Oncology Group (ECOG) performance status of </= 2
• Creatinine clearance > 40 mL/min
• Absolute neutrophil count (ANC) >/= 1,200/mm3
• Platelets >/= 75,000/mm3
• Lymphocytes >/= 5,000/mm3 in Phase 1b

Exclusion Criteria:

• Treatment with rituximab or other B-cell depleting agent within 30 days or alemtuzumab within 12 weeks
• Previous anticancer therapy within 30 days
• Refractory to prior fludarabine or other purine analog therapy either as a single agent or in combination
• Receipt of prior bendamustine or TRU-016
• Receipt of an investigational therapy or major surgery within 30 days
• Previous or concurrent additional malignancy (some exceptions apply)
• Any significant concurrent medical diseases or conditions
• Positive serology for HIV or hepatitis C, hepatitis B surface antigen positive or hepatitis B core antibody positive.
• Pregnant or breast feeding
• Drug or alcohol abuse
• Allergic to mannitol