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
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|ClinicalTrials.gov Identifier: NCT01646021|
Recruitment Status : Completed
First Posted : July 20, 2012
Results First Posted : March 1, 2017
Last Update Posted : January 19, 2018
|Condition or disease||Intervention/treatment||Phase|
|Mantle Cell Lymphoma||Drug: Ibrutinib Drug: Temsirolimus||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||280 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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 Mantle Cell Lymphoma Who Have Received at Least One Prior Therapy|
|Actual Study Start Date :||December 10, 2012|
|Primary Completion Date :||June 5, 2015|
|Study Completion Date :||December 15, 2016|
560 mg once daily continuous (without interruption) by mouth for 21-day cycles
175 mg once daily intravenous infusion on Days 1, 8, 15 of the first cycle followed by 75 mg on Days 1, 8, 15 of each 21-day cycle
- Progression Free Survival (PFS) [ Time Frame: Time from the date of randomization until the date of first documented evidence of progressive disease (or relapse for subjects who experience CR during the study) or death, whichever occurred first (approximately 48 months) ]PFS is defined as the duration in months from the date of randomization to the date of progression disease (PD) or relapse from complete response (CR) or death whichever was reported first and was assessed based on the investigator assessment. Revised Response Criteria for Malignant Lymphoma categorizes the response of the treatment of a patient's tumour to CR (the disappearance of all evidence of disease), Relapsed Disease or PD (Any new lesion or increase by greater than or equal to [>=] 50 percent [%] of previously involved sites from nadir).
- Overall Response Rate (ORR) [ Time Frame: Approximately up to 48 months ]ORR is defined as the percentage of participants who achieved either CR or PR as best overall response based on the investigator assessment. CR is Disappearance of all target lesions while PR is greater than or equal to 30 % decrease in the sum of the longest diameter of target lesions and Overall Response (OR) is sum of CR and PR.
- Overall Survival (OS) [ Time Frame: Approximately up to 48 months ]Overall survival (OS) was defined as the interval between the date of randomization and the date of death from any cause.
- Duration of Response [ Time Frame: Approximately up to 48 months ]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. The analysis was based on the investigator assessment.
- Time-to-Next Treatment [ Time Frame: Approximately up to 48 months ]Time to next treatment was measured from the date of randomization to the start date of any anti-neoplastic treatment subsequent to study treatment.
- Progression-Free Survival 2 [ Time Frame: Approximately up to 48 months ]Progression-free survival 2 defined as the time interval between the date of randomization and date of event, defined as progressive disease as assessed by investigator that started after the next line of subsequent anti-neoplastic therapy (including cross-over to ibrutinib), death from any cause, or the start of the second subsequent anti-neoplastic therapy if no progressive disease was recorded after the first subsequent anti-neoplastic therapy.
- Time to Worsening in the Lymphoma Sub Scale of Functional Assessment of Cancer Therapy- Lymphoma (FACT-Lym) [ Time Frame: Approximately up to 48 months ]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. Higher scores indicate a better quality of life.
- Number of Participants Affected With Treatment-emergent Adverse Events [ Time Frame: Time from first dose of study drug until the last dose date + 30 days or the start of a subsequent anti-neoplastic therapy, whichever occur earlier (Approximately up to 4 years) ]An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
- Time to Response [ Time Frame: Approximately up to 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.
- Extent of Exposure of Time [ Time Frame: Approximately up to 46.8 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.
- 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.
- 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 (Each cycle is of 21 days) ]The AUC-ss is the area under the plasma concentration time curve observed during steady state.
- Number of Participants With Biomarkers 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 up to 28.2 months ]Biomarker evaluations to identify markers altering BCR signaling or activate alternative signaling pathways and explore their association with response or resistance to ibrutinib. Next-generation sequencing at baseline identifies possible primary resistance mutations and those found only at progression are acquired mutations on therapy.
- Number of Hospitalizations Reported Related Medical Resource Utilization Information (MRUI) [ Time Frame: Approximately up to 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 up to 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 up to 28.2 months ]Medical resource utilization data associated with medical encounters related to disease was reported for all participants throughout the study.
- 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 (approximately up to 23 months) ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01646021
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|Study Director:||Janssen Research & Development, LLC Clinical Trial||Janssen Research & Development, LLC|