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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Chronic Lymphocytic Leukemia (CLL)

Intervention / Treatment
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* Drug: TRU-016 and bendamustine
* Drug: Bendamustine
* Drug: 15 mg/kg TRU-016 and bendamustine
* Drug: 20 mg/kg TRU-016 and bendamustine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1: 15 mg/kg TRU-016 + Bendamustine<br>TRU-016 (15 mg/kg) and bendamustine (70 mg/m2), n = 6 patients | Drug: 15 mg/kg TRU-016 and bendamustine<br>* TRU-016 at 15 mg/kg, weekly by IV infusion x 2 cycles, then every 14 days x 4 cycles PLUS bendamustine (70 mg/m2 by IV infusion on Days 1 and 2 of every 28-day cycle, for 6 cycles<br>|
| Experimental: Phase 1: 20 mg/kg TRU-016 + Bendamustine<br>TRU-016 (20 mg/kg) and bendamustine (70 mg/m2), n = 6 patients | Drug: 20 mg/kg TRU-016 and bendamustine<br>* TRU-016 at 20 mg/kg, weekly by IV infusion x 2 cycles, then every 14 days x 4 cycles PLUS bendamustine (70 mg/m2 by IV infusion on Days 1 and 2 of every 28-day cycle, for 6 cycles<br>|
| Experimental: Phase 2: TRU-016 and bendamustine<br>TRU-016 (20 mg/kg) and bendamustine (70 mg/m2), n = 32 patients | Drug: TRU-016 and bendamustine<br>* TRU-016 at 20 mg/kg, weekly by IV infusion x 2 cycles, then every 14 days x 4 cycles PLUS bendamustine (70 mg/m2 by IV infusion on Days 1 and 2 of every 28-day cycle, for 6 cycles<br>|
| Active Comparator: Phase 2: Bendamustine<br>Bendamustine (70 mg/m2), n = 33 patients | Drug: Bendamustine<br>* Bendamustine at 70 mg/m2 by IV infusion on Days 1 and 2 of every 28-day cycle, for 6 cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Per International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Criteria | 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. | 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Per NCI Criteria | Overall response rate per National Cancer Institute (NCI) Working group 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CLL, TRU-016, chronic lymphocytic leukemia, relapsed CLL, bendamustine