A Phase 3 interventional study of Ibrutinib in Graft vs Host Disease, sponsored by Janssen Pharmaceutical K.K.. Completed at 15 sites in Japan. Open to participants aged 12 Years and older. Per ClinicalTrials.gov, last updated 2025-02-04.
Sponsored by Janssen Pharmaceutical K.K. · Phase 3, Interventional, and Treatment
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]).
Exclusion Criteria:
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.
Also known as: PCI-32765, JNJ-54179060
Overall Response Rate (ORR)
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.
Time frame: Up to 3 year 6 months
Sustained Response Rate
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.
Time frame: Up to 3 year 6 months
Duration of Response (DOR)
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.
Time frame: Up to 3 year 6 months
cGVHD Response Rate at Each Timepoints
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.
Time frame: Weeks 5, 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157
Change in the Amount of Corticosteroid Required Over Time
Change in the amount of corticosteroid required over time was reported.
Time frame: Baseline, Weeks 24, 48, 96, and 144
Percentage of Participants With Overall Improvement in Lee cGVHD Symptom Scale Score
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).
Time frame: Up to 3 year 6 months
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
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.
Time frame: 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
AUC(0-last) is defined as area under the plasma concentration-time curve from time zero to time of last measurable concentration of ibrutinib.
Time frame: 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
AUC(0-24) is defined as area under the plasma concentration-time curve from time zero to 24 hours of ibrutinib.
Time frame: 0 to 24 hours (Day 1 of Weeks 1 and 2)
Maximum Observed Plasma Concentration (Cmax) of Ibrutinib
Cmax is defined as maximum observed plasma concentration of ibrutinib.
Time frame: Day 1 of Weeks 1 and 2
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Ibrutinib
Tmax is defined as time to reach the maximum observed plasma concentration of ibrutinib.
Time frame: Day 1 of Weeks 1 and 2
Elimination Half-Life (t1/2) of Ibrutinib
T1/2 is defined as elimination half-life of ibrutinib.
Time frame: Day 1 of Weeks 1 and 2
Apparent Clearance (CL/F) of Ibrutinib
CL/F is defined as apparent clearance of ibrutinib.
Time frame: Day 1 of Weeks 1 and 2
Apparent Volume of Distribution (Vd/F) of Ibrutinib
Vd/F is defined as apparent volume of distribution of ibrutinib.
Time frame: 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
AUC(0-infinity) is defined as area under the plasma concentration-time curve from time zero to infinite time of ibrutinib.
Time frame: 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
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.
Time frame: 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
AUC(0-24) is defined as area under the plasma concentration-time curve from time zero to 24 hours of PCI-45227.
Time frame: 0 to 24 hours (Day 1 of Weeks 1 and 2)
Maximum Observed Plasma Concentration (Cmax) of PCI-45227
Cmax is defined as maximum observed plasma concentration of PCI-45227.
Time frame: Day 1 of Weeks 1 and 2
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PCI-45227
Tmax is defined as time to reach the maximum observed plasma concentration of PCI-45227.
Time frame: Day 1 of Weeks 1 and 2
Elimination Half-Life (t1/2) of PCI-45227
T1/2 is defined as elimination half-life of PCI-45227.
Time frame: Day 1 of Weeks 1 and 2
Apparent Clearance (CL/F) of PCI-45227
CL/F is defined as apparent clearance of PCI-45227.
Time frame: Day 1 of Weeks 1 and 2
Apparent Volume of Distribution (Vd/F) of PCI-45227
Vd/F is defined as apparent volume of distribution of PCI-45227.
Time frame: 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
AUC(0-infinity) is defined as area under the plasma concentration-time curve from time zero to infinite time of PCI-45227.
Time frame: Day 1 of Weeks 1 and 2
| Milestone | Ibrutinib 420 mg |
|---|---|
| Started | 19 |
| Completed | 11 |
| Not completed | 8 |
| Withdrew: Death | 7 |
| Withdrew: Withdrawal by subject | 1 |
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.
| Percentage of participants | Ibrutinib 420 mg |
|---|---|
| Overall Response Rate (ORR) | 84.2 |
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.
| Percentage of participants | Ibrutinib 420 mg |
|---|---|
| Sustained Response Rate | 68.8 |
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.
| Months | Ibrutinib 420 mg |
|---|---|
| Duration of Response (DOR) | NA (5.30 to NA) |
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.
| Percentage of participants | Ibrutinib 420 mg |
|---|---|
| Week 5 | 26.3 (9.1 to 51.2) |
| Week 13 | 42.1 (20.3 to 66.5) |
| Week 25 | 52.6 (28.9 to 75.6) |
| Week 37 | 47.4 (24.4 to 71.1) |
| Week 49 | 47.4 (24.4 to 71.1) |
| Week 61 | 42.1 (20.3 to 66.5) |
| Week 73 | 36.8 (16.3 to 61.6) |
| Week 85 | 31.6 (12.6 to 56.6) |
| Week 97 | 31.6 (12.6 to 56.6) |
| Week 109 | 31.6 (12.6 to 56.6) |
| Week 121 | 36.8 (16.3 to 61.6) |
| Week 133 | 31.6 (12.6 to 56.6) |
| Week 145 | 26.3 (9.1 to 51.2) |
| Week 157 | 10.5 (1.3 to 33.1) |
Change in the amount of corticosteroid required over time was reported.
| Milligrams per kilograms per day | Ibrutinib 420 mg |
|---|---|
| Baseline | 0.270 (0.08 to 1.77) |
| Week 24 | 0.250 (0.08 to 0.87) |
| Week 48 | 0.150 (0.06 to 0.64) |
| Week 96 | 0.140 (0.01 to 0.59) |
| Week 144 | 0.140 (0.05 to 0.56) |
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).
| Percentage of participants | Ibrutinib 420 mg |
|---|---|
| Percentage of Participants With Overall Improvement in Lee cGVHD Symptom Scale Score | 52.6 (28.9 to 75.6) |
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.
| Participants | Ibrutinib 420 mg |
|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 19 |
AUC(0-last) is defined as area under the plasma concentration-time curve from time zero to time of last measurable concentration of ibrutinib.
| hours*nanograms per milliliter (h*ng/mL) | Ibrutinib 420 mg |
|---|---|
| Week 1: Day 1 | 3683.7 ± 3146.9 |
| Week 2: Day 1 | 4024.8 ± 4287.2 |
AUC(0-24) is defined as area under the plasma concentration-time curve from time zero to 24 hours of ibrutinib.
| hour*ng/mL | Ibrutinib 420 mg |
|---|---|
| Week 1: Day 1 | 2929.3 ± 1797.4 |
| Week 2: Day 1 | 4035.6 ± 4277.2 |
Cmax is defined as maximum observed plasma concentration of ibrutinib.
| Nanograms per milliliter (ng/mL) | Ibrutinib 420 mg |
|---|---|
| Week 1: Day 1 | 490.45 ± 366.07 |
| Week 2: Day 1 | 478.01 ± 508.08 |
Tmax is defined as time to reach the maximum observed plasma concentration of ibrutinib.
| Hours | Ibrutinib 420 mg |
|---|---|
| Week 1: Day 1 | 3.87 (1.78 to 5.75) |
| Week 2: Day 1 | 4.02 (1.75 to 5.43) |
T1/2 is defined as elimination half-life of ibrutinib.
| Hours | Ibrutinib 420 mg |
|---|---|
| Week 1: Day 1 | 4.9 (4.4 to 5.2) |
| Week 2: Day 1 | 4.4 (3.8 to 10.2) |
CL/F is defined as apparent clearance of ibrutinib.
| Milliliters per hour (mL/h) | Ibrutinib 420 mg |
|---|---|
| Week 1: Day 1 | 194211 ± 106164 |
| Week 2: Day 1 | 162457 ± 31966 |
Vd/F is defined as apparent volume of distribution of ibrutinib.
| Milliliters (mL) | Ibrutinib 420 mg |
|---|---|
| Week 1: Day 1 | 1350160 ± 748511 |
AUC(0-infinity) is defined as area under the plasma concentration-time curve from time zero to infinite time of ibrutinib.
| hour*ng/mL | Ibrutinib 420 mg |
|---|---|
| Week 1: Day 1 | 2643.8 ± 1656.2 |
| Week 2: Day 1 | 2659.2 ± 506.57 |
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.
| h*ng/mL | Ibrutinib 420 mg |
|---|---|
| Week 1: Day 1 | 1976.9 ± 968.83 |
| Week 2: Day 1 | 2547.6 ± 999.00 |
AUC(0-24) is defined as area under the plasma concentration-time curve from time zero to 24 hours of PCI-45227.
| hour*ng/mL | Ibrutinib 420 mg |
|---|---|
| Week 1: Day 1 | 1803.0 ± 585.84 |
| Week 2: Day 1 | 2547.6 ± 999.00 |
Cmax is defined as maximum observed plasma concentration of PCI-45227.
| ng/mL | Ibrutinib 420 mg |
|---|---|
| Week 1: Day 1 | 185.37 ± 91.874 |
| Week 2: Day 1 | 203.16 ± 82.292 |
Tmax is defined as time to reach the maximum observed plasma concentration of PCI-45227.
| Hours | Ibrutinib 420 mg |
|---|---|
| Week 1: Day 1 | 4.00 (1.88 to 6.18) |
| Week 2: Day 1 | 4.02 (0.00 to 5.28) |
T1/2 is defined as elimination half-life of PCI-45227.
| Hours | Ibrutinib 420 mg |
|---|---|
| Week 1: Day 1 | 5.9 (5.2 to 6.5) |
| Week 2: Day 1 | 5.4 (5.4 to 5.4) |
CL/F is defined as apparent clearance of PCI-45227.
| mL/h | Ibrutinib 420 mg |
|---|---|
| Week 1: Day 1 | 251681 ± 68392 |
| Week 2: Day 1 | 111922 ± NA |
Vd/F is defined as apparent volume of distribution of PCI-45227.
| mL | Ibrutinib 420 mg |
|---|---|
| Week 1: Day 1 | 2148283 ± 653626 |
AUC(0-infinity) is defined as area under the plasma concentration-time curve from time zero to infinite time of PCI-45227.
| hour*ng/mL | Ibrutinib 420 mg |
|---|---|
| Week 1: Day 1 | 1766.1 ± 478.74 |
| Week 2: Day 1 | 3752.6 ± NA |
Collected over Up to 3 year 6 months. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Ibrutinib 420 mg | 7/19 (36.8%) | 12/19 (63.2%) | 19/19 (100%) |
| Event | Ibrutinib 420 mg |
|---|---|
| PneumoniaInfections and infestations | 7/19 |
| CellulitisInfections and infestations | 3/19 |
| Renal ImpairmentRenal and urinary disorders | 2/19 |
| Immune ThrombocytopeniaBlood and lymphatic system disorders | 1/19 |
| Atrial FlutterCardiac disorders | 1/19 |
| CataractEye disorders | 1/19 |
| Gastrointestinal HaemorrhageGastrointestinal disorders | 1/19 |
| Multiple Organ Dysfunction SyndromeGeneral disorders | 1/19 |
| Liver DisorderHepatobiliary disorders | 1/19 |
| Anaphylactic ReactionImmune system disorders | 1/19 |
| Event | Ibrutinib 420 mg |
|---|---|
| StomatitisGastrointestinal disorders | 9/19 |
| CellulitisInfections and infestations | 6/19 |
| Upper Respiratory Tract InfectionInfections and infestations | 6/19 |
| Platelet Count DecreasedInvestigations | 6/19 |
| NauseaGastrointestinal disorders | 5/19 |
| PneumoniaInfections and infestations | 5/19 |
| CataractEye disorders | 4/19 |
| ConstipationGastrointestinal disorders | 4/19 |
| Oedema PeripheralGeneral disorders | 4/19 |
| HeadacheNervous system disorders | 4/19 |
| Age, Continuous(years) | Ibrutinib 420 mg |
|---|---|
| Mean | 40.5 ± 16.24 |
| Age, Customized(Participants) | Ibrutinib 420 mg |
|---|---|
| Less Than or Equal to 17 years (adolescent) | 1 |
| From 18 to 64 years | 18 |
| Sex: Female, Male(Participants) | Ibrutinib 420 mg |
|---|---|
| Female | 7 |
| Male | 12 |
| Ethnicity (NIH/OMB)(Participants) | Ibrutinib 420 mg |
|---|---|
| Hispanic or Latino | 0 |
| Not Hispanic or Latino | 19 |
| Unknown or Not Reported | 0 |
| Race (NIH/OMB)(Participants) | Ibrutinib 420 mg |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 19 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 0 |
| White | 0 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
| Region of Enrollment(Participants) | Ibrutinib 420 mg |
|---|---|
| JAPAN | 19 |
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Janssen Pharmaceutical K.K.