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Phase 1b Safety and Efficacy Study of TRU-016

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ClinicalTrials.gov Identifier: NCT01644253
Recruitment Status : Recruiting
First Posted : July 19, 2012
Last Update Posted : July 12, 2018
Sponsor:
Information provided by (Responsible Party):
Aptevo Therapeutics

July 12, 2012
July 19, 2012
July 12, 2018
September 2012
June 2019   (Final data collection date for primary outcome measure)
  • Incidence and severity of adverse events [ Time Frame: any time point during the study up to 18 months ]
  • CLL Cysteine 481 mutation status [ Time Frame: CLL patients in Cohort 7 will be followed for 9 months unless no cysteine 481 mutation is detected. ]
    The primary endpoint for Cohort 7 is the elimination of the cysteine 481 mutant clone (<1%).
Overall response rate (ORR) [ Time Frame: any time point during the study up to 18 months ]
ORR by the 2008 International Workshop on CLL (IWCLL) criteria
Complete list of historical versions of study NCT01644253 on ClinicalTrials.gov Archive Site
  • Overall Response Rate (ORR) [ Time Frame: any time point during the study up to 18 months ]
  • Progression-free survival (PFS) [ Time Frame: any time point during the study up to 18 months ]
  • Overall survival (OS) [ Time Frame: any time point during the study up to 18 months ]
  • Duration of response (DOR) [ Time Frame: any time point during the study up to 18 months ]
  • Resolution of disease-related symptoms [ Time Frame: any time point during the study up to 18 months ]
    Resolution of disease-related symptoms which are common to the disease include fever, weight loss, night sweats, fatigue, loss of appetite pain, and pruritus; symptoms will be assessed by descriptive statistics and data listings.
  • Maximum serum drug concentration (Cmax) [ Time Frame: any time point during the study up to 12 months ]
  • Minimum serum drug concentration (Cmin) [ Time Frame: any time point during the study up to 12 months ]
  • Area under the concentration-time curve (AUC0-t and AUC0-∞) [ Time Frame: any time point during the study up to 12 months ]
  • Systemic clearance (CL) [ Time Frame: any time point during the study up to 12 months ]
  • Volume of distribution (Vd) [ Time Frame: any time point during the study up to 12 months ]
  • Elimination half-life (t1/2) [ Time Frame: any time point during the study up to 12 months ]
Safety [ Time Frame: any time point during the study up to 18 months ]
The incidence and severity of adverse events, and changes from baseline in laboratory parameters, vital signs, and physical examination will be determined.
Not Provided
Not Provided
 
Phase 1b Safety and Efficacy Study of TRU-016
Phase 1b, Open Label Study to Evaluate Safety and Efficacy of TRU-016 in Combination With Rituximab, Obinutuzumab, Rituximab and Idelalisib, or Ibrutinib in Chronic Lymphocytic Leukemia and With Bendamustine in Peripheral T-cell Lymphoma
The purpose of this study is to evaluate the efficacy and safety of TRU-016 in combination with rituximab, in combination with obinutuzumab, in combination with rituximab and idelalisib, or in combination with ibrutinib in patients with CLL; and in combination with bendamustine in patients with PTCL.

The study will consist of 8 dose cohorts:

  1. Previously untreated patients 20 mg/kg TRU-016 + rituximab.
  2. Relapsed patients, 20 mg/kg TRU-016 + rituximab.
  3. Previously untreated patients 10 mg/kg TRU-016 + rituximab.
  4. Previously untreated patients TRU-016 + obinutuzumab.
  5. Relapsed patients, 20 mg/kg TRU-016 + rituximab + idelalisib.
  6. Patients with CLL on ibrutinib or another BTK inhibitor for a total of more than 1 year who have not had a complete response (CR) will continue receiving ibrutinib or another BTK inhibitor.
  7. Patients with CLL on ibrutinib or another BTK inhibitor with stable disease and in whom the cysteine 481 mutant clone is present at a level >1%, will continue receiving ibrutinib or the alternative BTK inhibitor.
  8. Patients with relapsed or refractory PTCL will receive TRU-016 dosed 10 mg/kg for the first dose and then 20 mg/kg weekly for 2 cycles, followed by dosing every other week for an additional 4 cycles (cycle = 28 days) + bendamustine for 2 days every cycle for 6 cycles.
Interventional
Phase 1
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Chronic Lymphocytic Leukemia
  • Peripheral T-cell Lymphoma
  • Biological: 20 mg/kg TRU-016 + Rituximab

    TRU-016: 10 mg/kg for first dose, all subsequent doses 20 mg/kg, IV once weekly for 8 weeks followed by 4 monthly doses

    Rituximab: 375 mg/m2 for first dose, all subsequent doses 500 mg/m2, IV once weekly for 8 weeks followed by 4 monthly doses

    Other Name: Rituxan
  • Biological: 10 mg/kg TRU-016 + Rituximab

    TRU-016: 6 mg/kg for first dose, all subsequent doses 10 mg/kg, IV on Day 1, 8 and 15, followed by 5 monthly doses

    Rituximab: 375 mg/m2 for first dose, all subsequent doses 500 mg/m2, IV following TRU-016 schedule

    Other Name: Rituxan
  • Biological: TRU-016 20 mg/kg + Obinutuzumab

    TRU-016: 6 mg/kg on Day 1, 20 mg/kg on Day 8 and 15, then 20 mg/kg once a month for 5 months

    Obinutuzumab: 100 mg on Day 1, 900 mg on Day 2, 1,000 mg on Day 8 and 15, then 1,000 mg once a month for 5 months

    Other Name: Gazyva
  • Biological: TRU-016 6-20 mg/kg + idelalisib + rituximab
    TRU-016: 6 mg/kg on Days 15-36 weekly, 10 mg/kg on Days 43 and 50, then 20 mg/kg once a month for 5 months.
    Other Name: Zydelig, Rituxan
  • Biological: TRU-016 10-20 mg/kg + ibrutinib
    TRU-016: Dosed weekly for 8 weeks followed by 4 monthly intravenous (IV) infusions. The first dose will be 10 mg/kg and all subsequent doses will be 20 mg/kg.
    Other Name: Imbruvica
  • Biological: TRU-016 10-20 mg/kg + bendamustine
    TRU-016 dosed 10 mg/kg for the first dose and then 20 mg/kg weekly for 2 cycles, followed by dosing every other week for an additional 4 cycles (cycle = 28 days). Bendamustine (90 mg/m2 on days 2 and 3 of cycle 1 and then days 1 and 2 of cycles 2 to 6) will be infused after completion of TRU-016. If a patient is benefiting with stable disease or better, then TRU-016 may continue to be dosed every 3 weeks after the first 6 cycles; bendamustine will not be dosed beyond 6 cycles.
  • Experimental: Cohort 1 - Previously Untreated CLL
    20 mg/kg TRU-016 + Rituximab
    Intervention: Biological: 20 mg/kg TRU-016 + Rituximab
  • Experimental: Cohort 2 - Relapsed CLL
    20 mg/kg TRU-016 + Rituximab
    Intervention: Biological: 20 mg/kg TRU-016 + Rituximab
  • Experimental: Cohort 3 - Previously Untreated CLL
    10 mg/kg TRU-016 + Rituximab
    Intervention: Biological: 10 mg/kg TRU-016 + Rituximab
  • Experimental: Cohort 4 - Previously Untreated CLL
    20 mg/kg TRU-016 20 + Obinutuzumab
    Intervention: Biological: TRU-016 20 mg/kg + Obinutuzumab
  • Experimental: Cohort 5 - Relapse CLL
    20 mg/kg TRU-016 + idelalisib + rituximab
    Intervention: Biological: TRU-016 6-20 mg/kg + idelalisib + rituximab
  • Experimental: Cohort 6 - With CLL on ibrutinib with no complete response
    20 mg/kg TRU-016 + ibrutinib
    Intervention: Biological: TRU-016 10-20 mg/kg + ibrutinib
  • Experimental: Cohort 7 - With CLL on ibrutinib with stable disease
    20 mg/kg TRU-016 + ibrutinib
    Intervention: Biological: TRU-016 10-20 mg/kg + ibrutinib
  • Experimental: Cohort 8 - With relapsed or refractory PTCL
    20 mg/kg TRU-016 + 90 mg/m2 bendamustine
    Intervention: Biological: TRU-016 10-20 mg/kg + bendamustine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
123
24
December 2019
June 2019   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Diagnosis of CLL by 2008 IWCLL criteria and with Rai stage intermediate or high risk CLL. Cohort 8 patients must have a diagnosis of PTCL.
  • No prior therapy for CLL for Cohorts 1, 3 and 4. For Cohort 2, 1-3 prior treatments. For Cohort 5, patients must have failed to respond or relapsed after 1 or more treatment regimens. For Cohort 6, patients who have been receiving ibrutinib for at least 12 months, have not had a CR, and in whom no cysteine 481 mutation is detected. For Cohort 7, patients who are receiving ibrutinib with stable disease and now have the cysteine 481 mutant clone present at levels of >1%. For Cohort 8, have refractory or relapsed PTCL after one or more prior therapies.
  • At least one of the following criteria for active disease requiring treatment: progressive splenomegaly and/or lymphadenopathy; anemia or thrombocytopenia due to bone marrow involvement; or progressive lymphocytosis with an increase of >50% over a 2-month period or an unanticipated doubling time of less than 6 months
  • For Cohorts 1, 3 and 4, contraindication to chemotherapy as first-line therapy due to patient age, comorbidity or patient preference
  • Age >/= to 18 years
  • ECOG performance status of </= 2
  • Life expectancy > 6 months in opinion of Investigator
  • Serum creatinine, total bilirubin, ALT/SGPT </= 2.0 x upper limit of normal
  • ANC >/= 800/mm3, Cohort 8 (PTCL): ANC >/= 1000/mm3
  • Platelets >/= 30,000/mm3

Exclusion Criteria:

  • For Cohorts 1, 3 and 4 only: Has received treatment with rituximab, alemtuzumab, ofatumumab or any other chemotherapeutic agent for CLL. Cohort 8: Received prior treatment with bendamustine and did not respond during treatment or relapsed less than sex months after completing treatment.
  • Has received an investigational therapy within 30 days of first dose of study drug
  • Previous or concurrent additional malignancy
  • Clinically significant pulmonary dysfunction, active infection, prior allogeneic bone marrow transplant, active autoimmune disease
  • Positive serology for HIV or hepatitis C
  • Hepatitis B surface antigen or hepatitis B core antibody positive
  • Pregnant or breastfeeding
  • Known current drug or alcohol abuse
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
No
Contact: David Schaaf 206-859-6655 schaafd@apvo.com
United States
 
 
NCT01644253
16009
No
Not Provided
Not Provided
Aptevo Therapeutics
Aptevo Therapeutics
Not Provided
Study Director: Scott C. Stromatt, M.D. Aptevo Therapeutics
Aptevo Therapeutics
July 2018

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