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

Chronic Lymphocytic Leukemia (CLL) Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01188681
• Other study ID #: 16201
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: September 2010
• Est. completion date: December 2014

Study information

• Verified date: May 2021
• Source: Aptevo Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 79
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia (CLL)
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

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

Locations

Country	Name	City	State
Austria	For additional information regarding sites for this trial call (919) 465-4648	Vienna
Germany	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	Gottingen
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
Poland	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
Spain	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
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	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	Denver	Colorado
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	Hackensack	New Jersey
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	Syracuse	New York

Sponsors (1)

Lead Sponsor	Collaborator
Aptevo Therapeutics

Countries where clinical trial is conducted

United States,  Austria,  Germany,  Poland,  Spain, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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

External Links

•   Otlertuzumab and Bendamustine in Relapsed CLL