Clinical trial NCT01188681: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Chronic Lymphocytic Leukemia (CLL)
Keywords: CLL
TRU-016
chronic lymphocytic leukemia
relapsed CLL
bendamustine
Lead sponsor: Aptevo Therapeutics
Sponsor class: INDUSTRY
First posted: 2010-08-25
Enrollment: 79
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Response Per International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Criteria
timeFrame: 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 outcomes:
measure: Response Per NCI Criteria
timeFrame: 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
Other outcomes:
Locations:
city: Denver
country: United States
facility: For additional information regarding sites for this trial call (919) 465-4648
state: Colorado
city: Augusta
country: United States
facility: For additional information regarding sites for this trial call (919) 465-4648
state: Georgia
city: Chicago
country: United States
facility: For additional information regarding sites for this trial call (919) 465-4648
state: Illinois
city: Hackensack
country: United States
facility: For additional information regarding sites for this trial call (919) 465-4648
state: New Jersey
city: Syracuse
country: United States
facility: For additional information regarding sites for this trial call (919) 465-4648
state: New York
city: Durham
country: United States
facility: For additional information regarding sites for this trial call (919) 465-4648
state: North Carolina
city: Cleveland
country: United States
facility: For additional information regarding sites for this trial call (919) 465-4648
state: Ohio
city: Columbus
country: United States
facility: For additional information regarding sites for this trial call (919) 465-4648
state: Ohio
city: Seattle
country: United States
facility: For additional information regarding sites for this trial call (919) 465-4648
state: Washington
city: Vienna
country: Austria
facility: For additional information regarding sites for this trial call (919) 465-4648
city: Bremen
country: Germany
facility: For additional information regarding sites for this trial call (919) 465-4648
city: Cologne
country: Germany
facility: For additional information regarding sites for this trial call (919) 465-4648
city: Frankfurt
country: Germany
facility: For additional information regarding sites for this trial call (919) 465-4648
city: Gottingen
country: Germany
facility: For additional information regarding sites for this trial call (919) 465-4648
city: Kiel
country: Germany
facility: For additional information regarding sites for this trial call (919) 465-4648
city: Mainz
country: Germany
facility: For additional information regarding sites for this trial call (919) 465-4648
city: Mutlangen
country: Germany
facility: For additional information regarding sites for this trial call (919) 465-4648
city: Regensburg
country: Germany
facility: For additional information regarding sites for this trial call (919) 465-4648
city: Bialystok
country: Poland
facility: For additional information regarding sites for this trial call (919) 465-4648
city: Gdansk
country: Poland
facility: For additional information regarding sites for this trial call (919) 465-4648
city: Lodz
country: Poland
facility: For additional information regarding sites for this trial call (919) 465-4648
city: Poznan
country: Poland
facility: For additional information regarding sites for this trial call (919) 465-4648
city: Warsaw
country: Poland
facility: For additional information regarding sites for this trial call (919) 465-4648
city: Madrid
country: Spain
facility: For additional information regarding sites for this trial call (919) 465-4648
city: Navarre
country: Spain
facility: For additional information regarding sites for this trial call (919) 465-4648
Study officials:
affiliation: Emergent Product Development Seattle LLC
name: Scott Stromatt, MD
role: STUDY_DIRECTOR
References:
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.