A Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor Ibrutinib in Participants With Steroid Dependent/Refractory Chronic Graft Versus Host Disease (cGVHD)

January 31, 2025 updated by: Janssen Pharmaceutical K.K.

A Phase 3 Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor Ibrutinib in Subjects With Steroid Dependent/Refractory Chronic Graft Versus Host Disease (cGVHD)

The purpose of this study is to evaluate efficacy of ibrutinib in Japanese participants with steroid dependent/refractory chronic graft versus host disease (cGVHD) by measuring overall cGVHD response (complete response [CR] and partial response [PR] defined by National Institutes of Health [NIH] consensus development project criteria [2014]).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
19

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Japan
      • Anjo-shi, Japan, 446-8602
        • Anjo Kosei Hospital
      • Bunkyo ku, Japan, 113 8677
        • Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital
      • Hiroshima, Japan, 730-8619
        • Hiroshima Red Cross Hospital & Atomic-Bomb Survivors Hospital
      • Isehara, Japan, 259-1193
        • Tokai University Hospital
      • Izumi, Japan, 594-1101
        • Osaka Women's and Children's Hospital
      • Kobe City, Japan, 650 0047
        • Kobe City Medical Center General Hospital
      • Kumamoto-shi, Japan, 860-0008
        • National Hospital Organization Kumamoto Medical Center
      • Kurashiki, Japan, 710-8602
        • Kurashiki Central Hospital
      • Maebashi, Japan, 371-0821
        • Gunmaken Saiseikai Maebashi Hospital
      • Nagoya, Japan, 453-8511
        • Japanese Red Cross Nagoya Daiichi Hospital
      • Nishinomiya, Japan, 663-8501
        • The Hospital of Hyogo College of Medicine
      • Okayama, Japan, 700 8558
        • Okayama University Hospital
      • Osaka, Japan, 545 8586
        • Osaka City University Hospital
      • Sapporo-shi, Japan, 060-8648
        • Hokkaido University Hospital
      • Setagaya Ku, Japan, 157 8535
        • National Center for Child Health and Development

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

12 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Steroid dependent/refractory chronic graft versus host disease (cGVHD) defined as modified National Institutes of Health (NIH) criteria (2014) below at any time post-hematopoietic cell transplant (post-HCT): a) Dependent disease, defined as, when glucocorticoid (prednisolone doses greater than or equal to [>=] 0.25 milligram per kilogram per day (mg/kg/day)or >=0.5 milligram per kilogram (mg/kg) every other day) are needed to prevent recurrence or progression of manifestations as demonstrated by unsuccessful attempts to taper the dose to lower levels on at least 2 occasions, separated by at least 8 weeks. In case of inability to taper the dose to less than or equal to (<=)0.25 mg/kg/day or <=0.5 mg/kg every other day (prednisolone doses) due to recurrence or progression of cGVHD manifestations, it is considered as steroid-dependent disease if the lowest tapering dose of the second occasion is equal or higher than the lowest tapering dose of the first occasion; b) Refractory disease, defined as, when cGVHD manifestations progress despite the use of a regimen containing glucocorticoid (prednisolone at >=1 mg/kg/day for at least 1 week) or persist without improvement despite continued treatment with glucocorticoid (prednisolone at >=0.5 mg/kg/day or 1 mg/kg every other day) for at least 4 weeks
  • Participants must be receiving baseline systemic glucocorticoid therapy for cGVHD at study entry. The dose of steroids must be stable for 14 days prior to starting ibrutinib
  • At the time of trial enrollment, participants may be receiving other immunosuppressive therapies in addition to glucocorticoids. Immunosuppressant doses must be stable for 14 days prior to starting ibrutinib
  • Clinically stable or worsening cGVHD for a minimum of 14 days between screening and Day 1 cGVHD response assessment
  • Karnofsky or Lansky (participants less than [<]16 years) performance status >=60

Exclusion Criteria:

  • Active acute graft versus host disease (GVHD)
  • More than 3 previous systemic treatments for cGVHD. Treatment with glucocorticoids is considered a treatment for cGVHD and should be included in determining the number of previous treatments
  • History of treatment with a tyrosine kinase inhibitor (example [e.g.] imatinib), purine analogs, or other cancer chemotherapy in the 4 weeks prior to starting ibrutinib. Participants may have received ibrutinib pre-transplant for other reasons besides cGVHD such as for the treatment of leukemia or lymphoma
  • History of treatment with monoclonal T and B cell antibodies in the 8 weeks prior to starting ibrutinib
  • Vaccinated with live, attenuated vaccines within 4 weeks of first dose of ibrutinib

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Ibrutinib
Participants will receive 420 milligram (mg) oral ibrutinib once daily starting on Week 1 Day 1, unless they have intervening unacceptable toxicity or meet other criteria for participants discontinuation.
Drug: Ibrutinib
Participants will receive 420 mg (3 * 140 mg capsules) oral ibrutinib once daily starting on Week 1 Day 1, unless they have intervening unacceptable toxicity or meet other criteria for participants discontinuation.
Other Names:
  • PCI-32765
  • JNJ-54179060

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Overall Response Rate (ORR)
Time Frame: Up to 3 year 6 months
ORR is defined as the percentage of participants who achieve complete response (CR) or partial response (PR) in the absence of new therapy for chronic graft versus host disease (cGVHD) and absence of progression of underlying disease or death based on the National Institutes of Health (NIH) Consensus Development Project Criteria (2014). CR is defined as resolution of all manifestations in each organ or site; PR is defined as improvement in at least 1 organ or site without progression in any other organ or site; and chronic graft versus host disease (cGVHD) progression is defined as clinically meaningful worsening in 1 or more organs regardless of improvement in other organs.
Up to 3 year 6 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Sustained Response Rate
Time Frame: Up to 3 year 6 months
Sustained response rate was defined as percentage of participants with NIH defined CR or PR that was sustained for at least 20 weeks. CR is defined as resolution of all manifestations in each organ or site; PR is defined as improvement in at least 1 organ or site without progression in any other organ or site.
Up to 3 year 6 months
Duration of Response (DOR)
Time Frame: Up to 3 year 6 months
DOR is defined as the duration from the date of initial response (CR or PR) to the date of progressive cGVHD or death, whichever occurred first. CR is defined as resolution of all manifestations in each organ or site; PR is defined as improvement in at least 1 organ or site without progression in any other organ or site; and cGVHD progression is defined as clinically meaningful worsening in 1 or more organs regardless of improvement in other organs.
Up to 3 year 6 months
cGVHD Response Rate at Each Timepoints
Time Frame: Weeks 5, 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157
cGVHD response rate was defined as percentage of participants with NIH defined CR or PR at each timepoint. CR is defined as resolution of all manifestations in each organ or site; PR is defined as improvement in at least 1 organ or site without progression in any other organ or site.
Weeks 5, 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157
Change in the Amount of Corticosteroid Required Over Time
Time Frame: Baseline, Weeks 24, 48, 96, and 144
Change in the amount of corticosteroid required over time was reported.
Baseline, Weeks 24, 48, 96, and 144
Percentage of Participants With Overall Improvement in Lee cGVHD Symptom Scale Score
Time Frame: Up to 3 year 6 months
Percentage of participants with overall improvement in Lee cGVHD symptom scale score was reported. Lee cGVHD symptom scale is a patient-reported symptom scale used to measure symptom burden and has 7 subscales (Skin, Eyes and Mouth, Breathing, Eating and Digestion, Muscles and Joints, Energy, and Mental and Emotional) with ratings as follows: 0-Not at all, 1-Slightly, 2-Moderately, 3-Quite a bit, 4-Extremely, with lower values representing a better outcome. A score was calculated for each subscale by taking the mean of all items completed if more than 50% were answered and normalizing to a 0 to 100 with a higher score indicating worse symptoms. An overall score was calculated as the average of these 7 subscales if at least 4 subscales had valid scores. A change of greater than or equal to (>=) 7 points on the Lee cGVHD symptom scale overall score was considered significant and relates to improvement in quality of life (QoL).
Up to 3 year 6 months
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time Frame: Up to 3 year 6 months
An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. TEAEs are adverse events with onset during the treatment phase or that were a consequence of a preexisting condition that has worsened since baseline, and occurred during treatment or within 30 days following the last dose of study treatment, or any adverse event that was considered study treatment-related regardless of the start date of the event.
Up to 3 year 6 months
Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (AUC [0-last]) of Ibrutinib
Time Frame: Day 1 of Weeks 1 and 2
AUC(0-last) is defined as area under the plasma concentration-time curve from time zero to time of last measurable concentration of ibrutinib.
Day 1 of Weeks 1 and 2
Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC [0-24]) of Ibrutinib
Time Frame: 0 to 24 hours (Day 1 of Weeks 1 and 2)
AUC(0-24) is defined as area under the plasma concentration-time curve from time zero to 24 hours of ibrutinib.
0 to 24 hours (Day 1 of Weeks 1 and 2)
Maximum Observed Plasma Concentration (Cmax) of Ibrutinib
Time Frame: Day 1 of Weeks 1 and 2
Cmax is defined as maximum observed plasma concentration of ibrutinib.
Day 1 of Weeks 1 and 2
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Ibrutinib
Time Frame: Day 1 of Weeks 1 and 2
Tmax is defined as time to reach the maximum observed plasma concentration of ibrutinib.
Day 1 of Weeks 1 and 2
Elimination Half-Life (t1/2) of Ibrutinib
Time Frame: Day 1 of Weeks 1 and 2
T1/2 is defined as elimination half-life of ibrutinib.
Day 1 of Weeks 1 and 2
Apparent Clearance (CL/F) of Ibrutinib
Time Frame: Day 1 of Weeks 1 and 2
CL/F is defined as apparent clearance of ibrutinib.
Day 1 of Weeks 1 and 2
Apparent Volume of Distribution (Vd/F) of Ibrutinib
Time Frame: Day 1 of Weeks 1 and 2
Vd/F is defined as apparent volume of distribution of ibrutinib.
Day 1 of Weeks 1 and 2
Area Under the Plasma Concentration-time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Ibrutinib
Time Frame: Day 1 of Weeks 1 and 2
AUC(0-infinity) is defined as area under the plasma concentration-time curve from time zero to infinite time of ibrutinib.
Day 1 of Weeks 1 and 2
Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (AUC [0-last]) of PCI-45227
Time Frame: Day 1 of Weeks 1 and 2
AUC(0-last) is defined as area under the plasma concentration-time curve from time zero to time of last measurable concentration of PCI-45227.
Day 1 of Weeks 1 and 2
Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC [0-24]) of PCI-45227
Time Frame: 0 to 24 hours (Day 1 of Weeks 1 and 2)
AUC(0-24) is defined as area under the plasma concentration-time curve from time zero to 24 hours of PCI-45227.
0 to 24 hours (Day 1 of Weeks 1 and 2)
Maximum Observed Plasma Concentration (Cmax) of PCI-45227
Time Frame: Day 1 of Weeks 1 and 2
Cmax is defined as maximum observed plasma concentration of PCI-45227.
Day 1 of Weeks 1 and 2
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PCI-45227
Time Frame: Day 1 of Weeks 1 and 2
Tmax is defined as time to reach the maximum observed plasma concentration of PCI-45227.
Day 1 of Weeks 1 and 2
Elimination Half-Life (t1/2) of PCI-45227
Time Frame: Day 1 of Weeks 1 and 2
T1/2 is defined as elimination half-life of PCI-45227.
Day 1 of Weeks 1 and 2
Apparent Clearance (CL/F) of PCI-45227
Time Frame: Day 1 of Weeks 1 and 2
CL/F is defined as apparent clearance of PCI-45227.
Day 1 of Weeks 1 and 2
Apparent Volume of Distribution (Vd/F) of PCI-45227
Time Frame: Day 1 of Weeks 1 and 2
Vd/F is defined as apparent volume of distribution of PCI-45227.
Day 1 of Weeks 1 and 2
Area Under the Plasma Concentration-time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of PCI-45227
Time Frame: Day 1 of Weeks 1 and 2
AUC(0-infinity) is defined as area under the plasma concentration-time curve from time zero to infinite time of PCI-45227.
Day 1 of Weeks 1 and 2

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Janssen Pharmaceutical K.K.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Janssen Pharmaceutical K.K., Japan Clinical Trial, Janssen Pharmaceutical K.K.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 29, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 29, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 16, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 16, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 22, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 31, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CR108443
  • 54179060GVH3001 (Other Identifier: Janssen Pharmaceutical K.K., Japan)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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