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

• ClinicalTrials.gov Identifier: NCT01188681
• Recruitment Status: Completed
• First Posted: August 25, 2010
• Results First Posted: January 6, 2017
• Last Update Posted: June 10, 2021
• Sponsor: Aptevo Therapeutics
• Information provided by (Responsible Party): Aptevo Therapeutics

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Chronic Lymphocytic Leukemia (CLL)	Drug: TRU-016 and bendamustine; Drug: Bendamustine; Drug: 15 mg/kg TRU-016 and bendamustine; Drug: 20 mg/kg TRU-016 and bendamustine	Phase 1; Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 79 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: September 2010
• Actual Primary Completion Date: December 2014
• Actual Study Completion Date: December 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: Phase 1: 15 mg/kg TRU-016 + Bendamustine; TRU-016 (15 mg/kg) and bendamustine (70 mg/m2), n = 6 patients	Drug: 15 mg/kg TRU-016 and bendamustine; 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
Experimental: Phase 1: 20 mg/kg TRU-016 + Bendamustine; TRU-016 (20 mg/kg) and bendamustine (70 mg/m2), n = 6 patients	Drug: 20 mg/kg TRU-016 and bendamustine; 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
Experimental: Phase 2: TRU-016 and bendamustine; TRU-016 (20 mg/kg) and bendamustine (70 mg/m2), n = 32 patients	Drug: TRU-016 and bendamustine; 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
Active Comparator: Phase 2: Bendamustine; Bendamustine (70 mg/m2), n = 33 patients	Drug: Bendamustine; Bendamustine at 70 mg/m2 by IV infusion on Days 1 and 2 of every 28-day cycle, for 6 cycles

Outcome Measures

Primary Outcome Measures :

1. Response Per International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Criteria [ Time Frame: 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 :

1. Response Per NCI Criteria [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Colorado

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Denver, Colorado, United States, 80218

United States, Georgia

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Augusta, Georgia, United States, 30912

United States, Illinois

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Chicago, Illinois, United States, 60637

United States, New Jersey

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Hackensack, New Jersey, United States, 07601

United States, New York

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Syracuse, New York, United States, 13210

United States, North Carolina

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Durham, North Carolina, United States, 27710

United States, Ohio

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Cleveland, Ohio, United States, 44195

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Columbus, Ohio, United States, 43210

United States, Washington

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Seattle, Washington, United States, 98109

Austria

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Vienna, Austria

Germany

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Bremen, Germany

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Cologne, Germany

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Frankfurt, Germany

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Gottingen, Germany

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Kiel, Germany

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Mainz, Germany

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Mutlangen, Germany

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Regensburg, Germany

Poland

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Bialystok, Poland

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Gdansk, Poland

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Lodz, Poland

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Poznan, Poland

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Warsaw, Poland

Spain

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Madrid, Spain

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Navarre, Spain

Sponsors and Collaborators

Aptevo Therapeutics

Investigators

• Study Director: Scott Stromatt, MD; Emergent Product Development Seattle LLC

More Information

Additional Information:

Otlertuzumab and Bendamustine in Relapsed CLL 

Publications:

Robak T, Hellmann A, Kloczko J, Loscertales J, Lech-Maranda E, Pagel JM, Mato A, Byrd JC, Awan FT, Hebart H, Garcia-Marco JA, Hill BT, Hallek M, Eisenfeld AJ, Stromatt SC, Jaeger U. Randomized phase 2 study of otlertuzumab and bendamustine versus bendamustine in patients with relapsed chronic lymphocytic leukaemia. Br J Haematol. 2017 Feb;176(4):618-628. doi: 10.1111/bjh.14464. Epub 2016 Dec 15.

• Responsible Party: Aptevo Therapeutics
• ClinicalTrials.gov Identifier: NCT01188681
• Other Study ID Numbers: 16201
• First Posted: August 25, 2010
• Results First Posted: January 6, 2017
• Last Update Posted: June 10, 2021
• Last Verified: May 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Aptevo Therapeutics:

CLL; TRU-016; chronic lymphocytic leukemia; relapsed CLL; bendamustine

Additional relevant MeSH terms:

Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Bendamustine Hydrochloride; Immunoglobulin G; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs