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

Primary Purpose

Chronic Lymphocytic Leukemia (CLL)

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
TRU-016 and bendamustine
Bendamustine
15 mg/kg TRU-016 and bendamustine
20 mg/kg TRU-016 and bendamustine
Sponsored by
Aptevo Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Lymphocytic Leukemia (CLL) focused on measuring CLL, TRU-016, chronic lymphocytic leukemia, relapsed CLL, bendamustine

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Active Comparator

Arm Label

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

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

Phase 2: TRU-016 and bendamustine

Phase 2: Bendamustine

Arm Description

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

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

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Response Per NCI Criteria
Overall response rate per National Cancer Institute (NCI) Working group criteria.

Full Information

First Posted
August 20, 2010
Last Updated
May 26, 2021
Sponsor
Aptevo Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT01188681
Brief Title
Safety and Efficacy Study of TRU-016 Plus Bendamustine vs. Bendamustine in Relapsed Chronic Lymphocytic Leukemia
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 Type
Interventional

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
September 2010 (undefined)
Primary Completion Date
December 2014 (Actual)
Study Completion Date
December 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Aptevo Therapeutics

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Lymphocytic Leukemia (CLL)
Keywords
CLL, TRU-016, chronic lymphocytic leukemia, relapsed CLL, bendamustine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
79 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Phase 1: 15 mg/kg TRU-016 + Bendamustine
Arm Type
Experimental
Arm Description
TRU-016 (15 mg/kg) and bendamustine (70 mg/m2), n = 6 patients
Arm Title
Phase 1: 20 mg/kg TRU-016 + Bendamustine
Arm Type
Experimental
Arm Description
TRU-016 (20 mg/kg) and bendamustine (70 mg/m2), n = 6 patients
Arm Title
Phase 2: TRU-016 and bendamustine
Arm Type
Experimental
Arm Description
TRU-016 (20 mg/kg) and bendamustine (70 mg/m2), n = 32 patients
Arm Title
Phase 2: Bendamustine
Arm Type
Active Comparator
Arm Description
Bendamustine (70 mg/m2), n = 33 patients
Intervention Type
Drug
Intervention Name(s)
TRU-016 and bendamustine
Intervention Description
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
Intervention Name(s)
Bendamustine
Intervention Description
Bendamustine at 70 mg/m2 by IV infusion on Days 1 and 2 of every 28-day cycle, for 6 cycles
Intervention Type
Drug
Intervention Name(s)
15 mg/kg TRU-016 and bendamustine
Intervention Description
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
Intervention Name(s)
20 mg/kg TRU-016 and bendamustine
Intervention Description
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
Primary Outcome Measure Information:
Title
Response Per International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Criteria
Description
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.
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
Secondary Outcome Measure Information:
Title
Response Per NCI Criteria
Description
Overall response rate per National Cancer Institute (NCI) Working group 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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Scott Stromatt, MD
Organizational Affiliation
Emergent Product Development Seattle LLC
Official's Role
Study Director
Facility Information:
Facility Name
For additional information regarding sites for this trial call (919) 465-4648
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
For additional information regarding sites for this trial call (919) 465-4648
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
Facility Name
For additional information regarding sites for this trial call (919) 465-4648
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
For additional information regarding sites for this trial call (919) 465-4648
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
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City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Facility Name
For additional information regarding sites for this trial call (919) 465-4648
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
For additional information regarding sites for this trial call (919) 465-4648
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
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City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
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City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
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City
Vienna
Country
Austria
Facility Name
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City
Bremen
Country
Germany
Facility Name
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City
Cologne
Country
Germany
Facility Name
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City
Frankfurt
Country
Germany
Facility Name
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City
Gottingen
Country
Germany
Facility Name
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City
Kiel
Country
Germany
Facility Name
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City
Mainz
Country
Germany
Facility Name
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City
Mutlangen
Country
Germany
Facility Name
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City
Regensburg
Country
Germany
Facility Name
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City
Bialystok
Country
Poland
Facility Name
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City
Gdansk
Country
Poland
Facility Name
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City
Lodz
Country
Poland
Facility Name
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City
Poznan
Country
Poland
Facility Name
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City
Warsaw
Country
Poland
Facility Name
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City
Madrid
Country
Spain
Facility Name
For additional information regarding sites for this trial call (919) 465-4648
City
Navarre
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
27977057
Citation
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.
Results Reference
background
Links:
URL
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5324531/
Description
Otlertuzumab and Bendamustine in Relapsed CLL

Learn more about this trial

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

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