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

Phase 1

Completed

Interventions: Drug: TRU-016 and bendamustine
Drug: 20 mg/kg TRU-016 and bendamustine
Drug: 15 mg/kg TRU-016 and bendamustine
Drug: Bendamustine

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Phase 2: TRU-016 and bendamustine	TRU-016 and bendamustine	TRU-016 (20 mg/kg) and bendamustine (70 mg/m2), n = 32 patients
Phase 1: 20 mg/kg TRU-016 + Bendamustine	20 mg/kg TRU-016 and bendamustine	TRU-016 (20 mg/kg) and bendamustine (70 mg/m2), n = 6 patients
Phase 1: 15 mg/kg TRU-016 + Bendamustine	15 mg/kg TRU-016 and bendamustine	TRU-016 (15 mg/kg) and bendamustine (70 mg/m2), n = 6 patients
Phase 2: Bendamustine	Bendamustine	Bendamustine (70 mg/m2), n = 33 patients

Primary Outcome Measures

Name	Time	Method
Response Per International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Criteria	1 and 2 months after end of treatment, then every 3 months until disease progression, death, initiation of new therapy, study withdrawal, or 2 years	Patients had full clinical response assessment monthly during treatment, at the end of treatment (EOT) visit, 30 and 60 days after the EOT visit, and subsequently every 3 months until the earliest of progression of CLL, death, initiation of new therapy, withdrawal from the study, or completion of 18 months of follow-up evaluations. Clinical response assessment included physical examination with measurement of spleen, liver, and lymph nodes, disease-related symptoms, and laboratory measurements, specifically complete blood count (CBC) with differential.

Secondary Outcome Measures

Name	Time	Method
Response Per NCI Criteria	1 and 2 months after end of treatment, then every 3 months until disease progression, death, initiation of new therapy, study withdrawal, or 2 years	Overall response rate per National Cancer Institute (NCI) Working group criteria.