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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Emergent Product Development Seattle LLC
ClinicalTrials.gov Identifier:
NCT01188681
First received: August 20, 2010
Last updated: November 8, 2016
Last verified: September 2016

August 20, 2010
November 8, 2016
September 2010
December 2014   (Final data collection date for primary outcome measure)
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.
  • Phase 1b: occurence of dose limiting toxicities in each dose cohort. [ Time Frame: Phase 1b: following treatment of last patient enrolled with 2 cycles. ]
  • Phase 2: investigator-assessed overall response rate (ORR) by 2008 IWCLL Criteria. [ Time Frame: Phase 2: monthly until end of treatment (EOT), 30 and 60 days after EOT and every 3 months ]
Complete list of historical versions of study NCT01188681 on ClinicalTrials.gov Archive Site
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.
  • Complete response (CR) and ORR [ Time Frame: Monthly until EOT, 30 and 60 days after EOT and every 3 months thereafter ]
    1996 NCI Working Group Criteria
  • CR [ Time Frame: Monthly until EOT, 30 and 60 days after EOT and every 3 months thereafter ]
    2008 IWCLL Criteria
  • Progression-free survival (PFS) [ Time Frame: Monthly until EOT, 30 and 60 days after EOT and every 3 months thereafter ]
  • Overall survival (OS) [ Time Frame: Monthly until EOT, 30 and 60 days after EOT and every 3 months thereafter ]
  • Duration of overall response (DOR) [ Time Frame: Monthly until EOT, 30 and 60 days after EOT and every 3 months thereafter ]
  • Disease-related symptoms [ Time Frame: Monthly until EOT, 30 and 60 days after EOT and every 3 months thereafter ]
  • Occurrence of adverse events [ Time Frame: Before each TRU-016 or bendamustine infusion, at all post-treatment visits ]
  • Changes in laboratory parameters, vital signs and physical examinations [ Time Frame: Various throughout the study ]
Not Provided
Not Provided
 
Safety and Efficacy Study of TRU-016 Plus Bendamustine vs. Bendamustine in Relapsed Chronic Lymphocytic Leukemia
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
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.
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.
Interventional
Phase 1
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Chronic Lymphocytic Leukemia (CLL)
  • 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
  • Drug: Bendamustine
    Bendamustine at 70 mg/m2 by IV infusion on Days 1 and 2 of every 28-day cycle, for 6 cycles
  • 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
  • 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 1: 15 mg/kg TRU-016 + Bendamustine
    TRU-016 (15 mg/kg) and bendamustine (70 mg/m2), n = 6 patients
    Intervention: Drug: 15 mg/kg TRU-016 and bendamustine
  • Experimental: Phase 1: 20 mg/kg TRU-016 + Bendamustine
    TRU-016 (20 mg/kg) and bendamustine (70 mg/m2), n = 6 patients
    Intervention: Drug: 20 mg/kg TRU-016 and bendamustine
  • Experimental: Phase 2: TRU-016 and bendamustine
    TRU-016 (20 mg/kg) and bendamustine (70 mg/m2), n = 32 patients
    Intervention: Drug: TRU-016 and bendamustine
  • Active Comparator: Phase 2: Bendamustine
    Bendamustine (70 mg/m2), n = 33 patients
    Intervention: Drug: Bendamustine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
79
December 2014
December 2014   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Austria,   Germany,   Poland,   Spain
 
 
NCT01188681
16201
Yes
Not Provided
No
Not Provided
Emergent Product Development Seattle LLC
Emergent Product Development Seattle LLC
Not Provided
Study Director: Scott Stromatt, MD Emergent Product Development Seattle LLC
Emergent Product Development Seattle LLC
September 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP