Clinical Trial: A Study of the Efficacy of ABT-199 in Subjects With Relapsed/Refractory or Previously Untreated Chronic Lymphocytic Leukemia With the 17p Deletion

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Phase 2 Open-Label Study of the Efficacy of ABT-199 (GDC-0199) in Subjects With Relapsed/Refractory or Previously Untreated Chronic Lymphocytic Leukemia Harboring the 17p Delet

Brief Summary: This is a Phase 2, open label, multicenter, study evaluating the efficacy and safety of ABT-199 in relapsed or refractory subjects with CLL harboring 17p13 (TP53 locus) deletion. One hundred seven (107) subjects were enrolled in the main cohort, with evaluation of efficacy as the primary objective, and approximately 50 subjects will be enrolled in the safety expansion cohort to evaluate safety and updated tumor lysis syndrome prophylaxis and management measures. Enrollment into the main cohort is closed. Enrollment into the safety expansion cohort is closed.

Detailed Summary:
Sponsor: AbbVie

Current Primary Outcome:

• Efficacy will be measured by overall response rate (ORR) (Main Cohort) [ Time Frame: Measured up to 2 years after the last subject has enrolled on the study. ]
  To evaluate the efficacy of ABT-199 monotherapy in subjects with relapsed or refractory chronic lymphocytic leukemia (CLL) harboring the 17p deletion. (Main Cohort)
• Number of subjects with adverse events (Expanded Safety Cohort) [ Time Frame: Measured up to 5 years after the last subject has enrolled in the study. ]
  Subjects will be monitored for clinical and laboratory evidence of adverse events throughout the study. (Expanded Safety Cohort)
• Change in physical exam findings, including vital signs (Expanded Safety Cohort) [ Time Frame: Measured from Day -1 up to 2 years after the last subject has enrolled in the study. ]
  Body temperature, weight, blood pressure, heart rate. (Expanded Safety Cohort)
• Change in clinical laboratory test results (Expanded Safety Cohort) [ Time Frame: Measured from Day -1 up to 2 years after the last subject has enrolled in the study. ]
  Chemistry, hematology, urinalysis, viral serologies. (Expanded Safety Cohort)
• Change in cardiac assessment findings (Expanded Safety Cohort) [ Time Frame: Measured from Day -1 up to 2 years after the last subject has enrolled in the study. ]
  Electrocardiogram and Multi Gated Acquisition Scan and/or Echocardiogram. (Expanded Safety Cohort)
• Percentage of subjects with
  
  

  Original Primary Outcome: Efficacy will be measured by overall response rate (ORR) [ Time Frame: Measured up to 2 years after the last subject has enrolled on the study. ]

  To evaluate the efficacy of ABT-199 monotherapy in subjects with relapsed or refractory chronic lymphocytic leukemia (CLL) harboring the 17p deletion.
  
  
  

  Current Secondary Outcome:

  • Complete Remission (CR) rate [ Time Frame: Measured up to 2 years after the last subject has enrolled in the study. ]
    Complete remission rate per Independent Review Committee assessment, will be defined as the proportion of subjects who achieved a CR per the NCI-CWG (National Cancer Institute-Working Group) criteria.
  • Partial Remission (PR) rate [ Time Frame: Measured up to 2 years after the last subject has enrolled in the study. ]
    Partial remission rate per Independent Review Committee assessment, will be defined as the proportion of subjects who achieved a PR per the NCI-CWG criteria.
  • Duration of response [ Time Frame: Measured up to 2 years after the last subject has enrolled in the study. ]
    Duration of response will be defined as the number of days from the date of first response (Complete Remission or Partial Remission) per Independent Review Committee (IRC) assessment to the earliest recurrence or Progressive Disease per IRC assessment.
  • Progression-free survival [ Time Frame: Measured up to 5 years after the last subject has enrolled in the study. ]
    Progression-free survival will be defined as the number of days from the date of first dose to the date of earliest disease progression (per Independent Review Committee assessment) or death.
  • Time to progression [ Time Frame: Measured up to 5 years after the last subject has enrolled in the study ]
    Time to progression will be defined as the number of days from the date of first dose to the date of earliest disease progression (per Independent Review Committee assessment).
  • Overall survival [ Time Frame: Measured up to 5 years after the last subject has enrolled in the study. ]
    Overall survival will be defined as the number of days from the date of first dose to the date of death for all dosed subjects.
  • Percent of subjects who move on to stem cell transplant [ Time Frame: Measured up to 2 years after the last subject has enrolled in the study. ]
    The percent of subjects who move on to stem cell transplant will be summarized and the 95% confidence interval based on the binomial distribution will be provided.
  • Number of subjects with adverse events (Main Cohort) [ Time Frame: Measured up to 5 years after the last subject has enrolled in the study. ]
    Subjects will be monitored for clinical and laboratory evidence of adverse events throughout the study. (Main Cohort)
  • Change in physical exam findings, including vital signs (Main Cohort) [ Time Frame: Measured from Day -1 up to 2 years after the last subject has enrolled in the study. ]
    Body temperature, weight, blood pressure, heart rate. (Main Cohort)
  • Change in clinical laboratory test results (Main Cohort) [ Time Frame: Measured from Day -1 up to 2 years after the last subject has enrolled in the study. ]
    Chemistry, hematology, urinalysis, viral serologies. (Main Cohort)
  • Change in cardiac assessment findings (Main Cohort) [ Time Frame: Measured from Day -1 up to 2 years after the last subject has enrolled in the study. ]
    Electrocardiogram and Multi Gated Acquisition Scan and/or Echocardiogram. (Main Cohort)
  • Percentage of subjects with adverse events (Main Cohort) [ Time Frame: Measured up to 5 years after the last subject has enrolled in the study. ]
    Subjects will be monitored for clinical and laboratory evidence of adverse events throughout the study. (Main Cohort)
  • Overall Response Rate (ORR) (Expanded Safety Cohort) [ Time Frame: Measured up to 2 years after the last subject has enrolled on the study. ]
    To evaluate the efficacy of ABT-199 monotherapy in subjects with relapsed or refractory chronic lymphocytic leukemia (CLL) harboring the 17p deletion. (Expanded Safety Cohort)
  • Event free survival [ Time Frame: Measured up to 5 years after the last subject has enrolled in the study. ]
    Event-free survival is defined as the number of days from the date of first dose to the date of earliest disease progression, death, or start of a new anti-leukemic therapy.
  • Time to first response [ Time Frame: Measured up to 2 years after the last subject has enrolled in the study. ]
    Time to first response will be defined as the number of days from the date of first dose to the date of the first sign of response (CR, CRi, nPR, or PR) given the subject has had a CR, CRi, confirmed nPR or confirmed PR per the 2008 Modified IWCLL NCI-WG criteria.
  • Time to 50% reduction in absolute lymphocyte count [ Time 
    
    

    Original Secondary Outcome:

    • Complete Remission (CR) rate [ Time Frame: Measured up to 2 years after the last subject has enrolled in the study. ]
      Complete remission rate per Independent Review Committee assessment, will be defined as the proportion of subjects who achieved a CR per the NCI-CWG (National Cancer Institute-Working Group) criteria.
    • Partial Remission (PR) rate [ Time Frame: Measured up to 2 years after the last subject has enrolled in the study. ]
      Partial remission rate per Independent Review Committee assessment, will be defined as the proportion of subjects who achieved a PR per the NCI-CWG criteria.
    • Duration of response [ Time Frame: Measured up to 2 years after the last subject has enrolled in the study. ]
      Duration of response will be defined as the number of days from the date of first response (Complete Remission or Partial Remission) per Independent Review Committee (IRC) assessment to the earliest recurrence or Progressive Disease per IRC assessment.
    • Progression-free survival [ Time Frame: Measured up to 5 years after the last subject has enrolled in the study. ]
      Progression-free survival will be defined as the number of days from the date of first dose to the date of earliest disease progression (per Independent Review Committee assessment) or death.
    • Time to progression [ Time Frame: Measured up to 5 years after the last subject has enrolled in the study ]
      Time to progression will be defined as the number of days from the date of first dose to the date of earliest disease progression (per Independent Review Committee assessment).
    • Overall survival [ Time Frame: Measured up to 5 years after the last subject has enrolled in the study. ]
      Overall survival will be defined as the number of days from the date of first dose to the date of death for all dosed subjects.
    • Percent of subjects who move on to stem cell transplant [ Time Frame: Measured up to 2 years after the last subject has enrolled in the study. ]
      The percent of subjects who move on to stem cell transplant will be summarized and the 95% confidence interval based on the binomial distribution will be provided.
    • Number of subjects with adverse events [ Time Frame: Measured up to 5 years after the last subject has enrolled in the study. ]
      Subjects will be monitored for clinical and laboratory evidence of adverse events throughout the study.
    • Change in physical exam findings, including vital signs [ Time Frame: Measured from Day -1 up to 5 years after the last subject has enrolled in the study. ]
      Body temperature, weight, blood pressure, heart rate.
    • Change in clinical laboratory test results [ Time Frame: Measured from Day -1 up to 5 years after the last subject has enrolled in the study. ]
      Chemistry, hematology, urinalysis, viral serologies.
    • Change in cardiac assessment findings [ Time Frame: Measured from Day -1 up to 2 years after the last subject has enrolled in the study. ]
      Electrocardiogram and Multi Gated Acquisition Scan and/or Echocardiogram.
    • Percentage of subjects with adverse events [ Time Frame: Measured up to 5 years after the last subject has enrolled in the study. ]
      Subjects will be monitored for clinical and laboratory evidence of adverse events throughout the study.
    
    
    Information By: AbbVie
    

    Dates:
    Date Received: June 26, 2013
    Date Started: June 27, 2013
    Date Completion: May 12, 2020
    Last Updated: April 21, 2017
    Last Verified: April 2017