Clinical Trial: Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor Ibrutinib in Participants With Relapsed or Refractory Mantle Cell Lymphoma

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

Official Title: A Phase 2 Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor Ibrutinib in Subjects With Relapsed or Refractory Mantle Cell Lymphoma (MCL)

Brief Summary: The purpose of this study is to evaluate overall response rate (ORR) (complete response [CR] rate plus partial response [PR] rate) of ibrutinib (IMBRUVICA™; PCI-32765; JNJ-54179060), as assessed by an Independent Review Committee (IRC), in participants with relapsed or refractory mantle cell lymphoma (MCL-a cancer of the lymph nodes or tissues).

Detailed Summary: This is a Phase 2, single-arm, open-label (all knew the intervention of study), and multicenter (when more than 1 hospital or medical school team work on a medical research study) study to explore the efficacy, safety and pharmacokinetics (the study of the way a drug enters and leaves the blood and tissues over time) of ibrutinib in Japanese participants with relapsed (the return of a medical problem) or refractory (not responding to treatment) MCL. The study will consist of a Screening Phase of 30 days prior to first dose of study drug followed by treatment Phase and a post-treatment follow-up Phase. Participants will receive ibrutinib 560 milligram (mg) orally, once daily on a 28-day cycle until disease progression (or relapse if the participant achieved a CR), unacceptable toxicity, or study end, whichever occurs first. Treatment Phase will have disease assessments every 8 weeks up to 24 weeks after start of study drug, then every 12 weeks thereafter to assess efficacy up to 2 years after last participant enrolled. Efficacy will primarily be evaluated by ORR. Participants' safety will be monitored throughout the study.
Sponsor: Janssen Pharmaceutical K.K.

Current Primary Outcome: Percentage of Participants With Overall Response [ Time Frame: Up to 2 years after last participant enrolled ]

Overall response is defined as achievement of complete response (CR) or partial response (PR), as assessed by the Independent Review Committee (IRC), based on the Revised Response Criteria for Malignant Lymphoma. CR is: a) disappearance of all detectable disease symptoms and signs; b) lymph nodes and nodal masses must have regressed on computed tomography (CT) to normal size; c) negative positron emission tomography (PET) scan; d) normal sized spleen or liver if enlarged before therapy; d) bone marrow infiltrate must be cleared if would have been involved before treatment; e) no new sites of disease. PR is: a) greater than 50 percent decrease in the sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses, splenic and hepatic nodules; b) no increase in the size of other nodes, liver, or spleen, c) no measurable disease in other organs; d) no new sites of disease; e) 1 PET-positive site of disease (required for the CT+PET assessment of PR).


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Duration of Response [ Time Frame: Up to 2 years after last participant enrolled ]
    Duration of response is defined as the time from the date of initial documentation of a response (CR or PR) to the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death.
  • Time to Response [ Time Frame: Up to 2 years after last participant enrolled ]
    Time to response is the time from the date of first dose of study drug until the first date of initial documentation of a response (CR or PR).
  • Overall Survival (OS) [ Time Frame: Up to 2 years after last participant enrolled ]
    The OS is defined as the time from the date of first dose of study drug to date of death from any cause. If the participant is alive or the vital status is unknown, the participant will be censored at the date the participant will be last known to be alive.
  • Progression-free Survival (PFS) [ Time Frame: Up to 2 years after last participant enrolled ]
    The PFS is defined as the duration from the date of first dose of study drug until the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death, whichever comes first.
  • Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) [ Time Frame: Day 1 up to 30 days after last dose administration ]
    An AE is any untoward medical occurrence in a participant who will receive study drug without regard to possibility of causal relationship. An 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; or congenital anomaly.
  • Area Under the Plasma Concentration-Time Curve From Zero to Last Measurable Concentration (AUC [0-t]) [ Time Frame: Predose (0), 1, 2, and 4 hours postdose on Day 1 of Cycle 1 and 2 ]
    The AUC (0-last) is the area under the plasma concentration versus time curve from time zero to the time corresponding to the last quantifiable concentration.
  • Apparent Clearance (CL/F) [ Time Frame: Predose (0), 1, 2, and 4 hours postdose on Day 1 of Cycle 1 and 2 ]
    The CL/F is defined as the apparent total clearance of the drug from plasma after oral administration.
  • Minimum Observed Plasma Concentration (Cmin) [ Time Frame: Predose (0) and 1, 2, and 4 hours postdose on Day 1 of Cycle 1 and Cycle 2 ]
    Minimum Observed Plasma Concentration (Cmin) will be observed.


Original Secondary Outcome: Same as current

Information By: Janssen Pharmaceutical K.K.

Dates:
Date Received: June 19, 2014
Date Started: August 2014
Date Completion:
Last Updated: January 23, 2017
Last Verified: January 2017