Clinical Trial: Study of Ibrutinib (a Bruton's Tyrosine Kinase Inhibitor), Versus Temsirolimus in Patients With Relapsed or Refractory Mantle Cell Lymphoma Who Have Received at Least One Prior Therapy

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Randomized, Controlled, Open-Label, Multicenter Phase 3 Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib, Versus Temsirolimus in Subjects With Relapsed or Refractory



Original Primary Outcome: Progression free survival [ Time Frame: clinical cutoff (defined by 178 patients with progression free survival events; up to 3 years after the last patient is randomized) ]

Current Secondary Outcome:

  • Overall Response Rate (ORR) [ Time Frame: Approximately 28.2 months ]
    Overall response rate (ORR), defined as the percentage of participants who achieved either CR or PR as best overall response as assessed by Independent Review Committee (IRC) at or prior to initiation of subsequent antineoplastic therapy. Complete Response (CR) = Disappearance of all target lesions; Partial Response (PR)= greater than or equal to 30 percentage decrease in the sum of the longest diameter of target lesions and Overall Response (OR) = CR + PR.
  • Overall Survival (OS) [ Time Frame: Approximately 28.2 months ]
    Overall survival (OS), defined as the duration (months) from the date of randomization to the date of the participant's death from any cause.
  • One Year Survival Rate [ Time Frame: Month 12 ]
    One -year survival rate, defined as the proportion of participants who were alive 1 year after randomization.
  • Duration of Response [ Time Frame: approximately 2.8 years ]
    Duration of response (CR or PR), defined as the duration in days from the date of initial response to the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death.
  • Time-to-Next Treatment [ Time Frame: approximately 2.8 years ]
    Time to next treatment was measured from the date of randomization to the start date of any anti-lymphoma treatment subsequent to study treatment.
  • Time to Response [ Time Frame: Approximately 2.8 years ]
    Time to response for participants with CR/PR, defined as the interval between the date of randomization and date of initial documentation of response.
  • Time to Worsening in the Lymphoma Sub Scale of Functional Assessment of Cancer Therapy- Lymphoma (FACT-Lym) [ Time Frame: Approximately 2 years ]
    Time to worsening in the Lymphoma subscale of the FACT-Lym, defined as the interval from the date of randomization to the start date of worsening. Worsening was defined by a 5-point decrease from baseline. FACT-Lym Lymphoma subscale contains 15 questions, scores from 0 to 4 for each question (higher the worse). Lymphoma subscale score is the total of reverse scores, range 0 to 60.
  • The Mean Change From Baseline in Euro QoL Five-Dimension (EQ-5D-5L) Scores for Each Post Baseline Assessment [ Time Frame: Baseline, Cycle 2, 3, 4, 5, 6, 7, 8, 11, 14, 17, 20, 28, 36 and End of treatment ]
    The EQ-5D is a participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression, using 5 levels (1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and possible total score range -0.594 to 1; higher score indicates a better health state.
  • Area Under the Plasma Concentration of Ibrutinib During Steady State (AUC-ss) [ Time Frame: Cycle 1 and 2 (Day 1): Predose, 1, 2, 4 hr postdose; Cycle 3 (day 1): Predose ]
    The AUC-ss is the area under the plasma concentration time curve observed during steady state.
  • Number of Participants With Bio Markers That Alter B-cell Receptor (BCR) Signaling or Activate Alternative Signaling Pathways and to Explore Their Association With Response or Resistance to Ibrutinib [ Time Frame: Approximately upto 28.2 months ]
  • Extent of Exposure of Time [ Time Frame: Approximately upto 28.2 months ]
    Extent of exposure is defined as the duration of the treatment administered during the study. Duration of exposure is calculated as the number of months between the start and end of treatment.
  • Number of Hospitalizations Reported Related Medical Resource Utilization Information (MRUI) [ Time Frame: Approximately upto 28.2 months ]
    Medical resource utilization data associated with medical encounters related to disease was reported for all participants throughout the study.
  • Number of Emergency Room Visits Reported Related Medical Resource Utilization Information (MRUI) [ Time Frame: Approximately upto 28.2 months ]
    Medical resource utilization data associated with medical encounters related to disease was reported for all participants throughout the study.
  • Days of Hospitalization and Emergency Room Visits Reported Related Medical Resource Utilization Information (MRUI) [ Time Frame: Approximately upto 28.2 months ]
    Medical resource utilization data associated with medical encounters related

    Original Secondary Outcome:

    • Overall response rate [ Time Frame: up to 3 years after the last patient is randomized ]
    • Overall survival [ Time Frame: up to 3 years after the last patient is randomized ]
    • 1-year survival rate [ Time Frame: Month 12 ]
    • Duration of response [ Time Frame: up to 3 years after the last patient is randomized ]
    • Time-to-Next Treatment [ Time Frame: up to 3 years after the last patient is randomized ]
    • Number of participants with adverse events [ Time Frame: up to 30 days after the last dose of study medication ]
    • Mean plasma concentrations of ibrutinib [ Time Frame: Cycles 1-3: predose on Day 1; postdose at 1, 2, and 4 hours ]
    • Maximum observed plasma concentration of ibrutinib [ Time Frame: Cycles 1-3: predose on Day 1; postdose at 1, 2, and 4 hours ]
    • Minimum observed plasma concentration of ibrutinib [ Time Frame: Cycles 1-3: predose on Day 1; postdose at 1, 2, and 4 hours ]
    • Area under the plasma concentration-time curve from time 0 to 24 hours of ibrutinib [ Time Frame: Cycles 1-3: predose on Day 1; postdose at 1, 2, and 4 hours ]
    • Mean change from baseline in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) scale score [ Time Frame: up to 3 years after the last patient is randomized ]
    • Mean change from baseline in EuroQol (EQ-5D-5L) index score [ Time Frame: up to 3 years after the last patient is randomized ]
    • Mean change from baseline in medical resource utilization [ Time Frame: up to 30 days from last dose of study medication ]
    • Mean change from baseline in biomarkers that alter B-cell receptor (BCR) signaling or activate alternative signaling pathways [ Time Frame: up to 30 days from last dose of study medication ]
    • Mean change from baseline in identified resistance biomarkers from bone marrow [ Time Frame: up to 30 days from last dose of study medication ]


    Information By: Janssen Research & Development, LLC

    Dates:
    Date Received: July 18, 2012
    Date Started: December 2012
    Date Completion:
    Last Updated: January 11, 2017
    Last Verified: January 2017