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

NCT ID: NCT01188681

Last Updated: 2021-06-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 79 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-09-30
• Study Completion Date: 2014-12-31

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.

Conditions

Chronic Lymphocytic Leukemia (CLL)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 1: 15 mg/kg TRU-016 + Bendamustine

TRU-016 (15 mg/kg) and bendamustine (70 mg/m2), n = 6 patients

Group Type: EXPERIMENTAL

15 mg/kg TRU-016 and bendamustine

Intervention Type: DRUG

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

Phase 1: 20 mg/kg TRU-016 + Bendamustine

TRU-016 (20 mg/kg) and bendamustine (70 mg/m2), n = 6 patients

Group Type: EXPERIMENTAL

20 mg/kg TRU-016 and bendamustine

Intervention Type: DRUG

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

Phase 2: TRU-016 and bendamustine

TRU-016 (20 mg/kg) and bendamustine (70 mg/m2), n = 32 patients

Group Type: EXPERIMENTAL

TRU-016 and bendamustine

Intervention Type: DRUG

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

Phase 2: Bendamustine

Bendamustine (70 mg/m2), n = 33 patients

Group Type: ACTIVE_COMPARATOR

Bendamustine

Intervention Type: DRUG

Bendamustine at 70 mg/m2 by IV infusion on Days 1 and 2 of every 28-day cycle, for 6 cycles

Interventions

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

Intervention Type: DRUG

Bendamustine

Bendamustine at 70 mg/m2 by IV infusion on Days 1 and 2 of every 28-day cycle, for 6 cycles

Intervention Type: 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

Intervention Type: 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

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Aptevo Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Scott Stromatt, MD

Role: STUDY_DIRECTOR

Emergent Product Development Seattle LLC

Locations

For additional information regarding sites for this trial call (919) 465-4648

Denver, Colorado, United States

For additional information regarding sites for this trial call (919) 465-4648

Augusta, Georgia, United States

For additional information regarding sites for this trial call (919) 465-4648

Chicago, Illinois, United States

For additional information regarding sites for this trial call (919) 465-4648

Hackensack, New Jersey, United States

For additional information regarding sites for this trial call (919) 465-4648

Syracuse, New York, United States

For additional information regarding sites for this trial call (919) 465-4648

Durham, North Carolina, United States

For additional information regarding sites for this trial call (919) 465-4648

Cleveland, Ohio, United States

For additional information regarding sites for this trial call (919) 465-4648

Columbus, Ohio, United States

For additional information regarding sites for this trial call (919) 465-4648

Seattle, Washington, United States

For additional information regarding sites for this trial call (919) 465-4648

Vienna, , Austria

For additional information regarding sites for this trial call (919) 465-4648

Bremen, , Germany

For additional information regarding sites for this trial call (919) 465-4648

Cologne, , Germany

For additional information regarding sites for this trial call (919) 465-4648

Frankfurt, , Germany

For additional information regarding sites for this trial call (919) 465-4648

Göttingen, , Germany

For additional information regarding sites for this trial call (919) 465-4648

Kiel, , Germany

For additional information regarding sites for this trial call (919) 465-4648

Mainz, , Germany

For additional information regarding sites for this trial call (919) 465-4648

Mutlangen, , Germany

For additional information regarding sites for this trial call (919) 465-4648

Regensburg, , Germany

For additional information regarding sites for this trial call (919) 465-4648

Bialystok, , Poland

For additional information regarding sites for this trial call (919) 465-4648

Gdansk, , Poland

For additional information regarding sites for this trial call (919) 465-4648

Lodz, , Poland

For additional information regarding sites for this trial call (919) 465-4648

Poznan, , Poland

For additional information regarding sites for this trial call (919) 465-4648

Warsaw, , Poland

For additional information regarding sites for this trial call (919) 465-4648

Madrid, , Spain

For additional information regarding sites for this trial call (919) 465-4648

Navarre, , Spain

Countries

United States; Austria; Germany; Poland; Spain

References

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.

Reference Type: BACKGROUND

PMID: 27977057 (View on PubMed)

Related Links

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5324531/

Otlertuzumab and Bendamustine in Relapsed CLL

Other Identifiers

16201

Identifier Type: -

Identifier Source: org_study_id