- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03474679
A Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor Ibrutinib in Participants With Steroid Dependent/Refractory Chronic Graft Versus Host Disease (cGVHD)
December 30, 2021 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
Study Type
Interventional
Enrollment (Actual)
19
Phase
- 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
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Anjo-shi, Japan, 446-8602
- Anjo Kosei Hospital
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Bunkyo-ku, Japan, 113-8677
- Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital
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Hiroshima, Japan, 730-8619
- Hiroshima Red Cross Hospital & Atomic-Bomb Survivors Hospital
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Hyogo, Japan, 650-0047
- Kobe City Medical Center General Hospital
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Isehara, Japan, 259-1193
- Tokai University Hospital
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Izumi, Japan, 594-1101
- Osaka Women's and Children's Hospital
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Kumamoto, Japan, 860-0008
- National Hospital Organization Kumamoto Medical Center
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Kurashiki, Japan, 710-8602
- Kurashiki Central Hospital
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Maebashi, Japan, 371-0821
- Gunmaken Saiseikai Maebashi Hospital
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Nagoya, Japan, 453-8511
- Japanese Red Cross Nagoya Daiichi Hospital
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Nishinomiya, Japan, 663-8501
- The Hospital of Hyogo College of Medicine
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Okayama, Japan, 700-8558
- Okayama University Hospital
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Osaka, Japan, 545-8586
- Osaka City University Hospital
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Sapporo-shi, Japan, 060-8648
- Hokkaido University Hospital
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Setagaya-ku, Japan, 157-8535
- National Center for Child Health and Development
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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
Ages Eligible for Study
12 years and older (Child, Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
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 |
Intervention / Treatment |
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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.
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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:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Participants who Achieve Complete Response (CR) or Partial Response (PR) (i.e. Overall Response Rate [ORR])
Time Frame: Approximately up to 4.5 years
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ORR is defined as the percentage of participants who achieve complete response (CR) or partial response (PR).
Response is defined by the National Institutes of Health (NIH) Consensus Development Project Criteria (2014) and must occur, in the absence of new therapy for chronic graft versus host disease (cGVHD) and absence of progression of underlying disease or death.
CR: Resolution of all manifestations in each organ or site.
PR: Improvement in at least 1 organ or site without progression in any other organ or site.
cGVHD Progression: Clinically meaningful worsening in 1 or more organs regardless of improvement in other organs.
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Approximately up to 4.5 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Participants with Sustained Response
Time Frame: Approximately up to 4.5 years
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Percentage of participants with sustained response is defined as rate of NIH defined CR or PR that was sustained for at least 20 weeks.
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Approximately up to 4.5 years
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Duration of Response (DOR)
Time Frame: From the date of initial documentation of a response to the date of first documented evidence of progressive cGVHD or death, whichever occurs first (approximately up to 4.5 years)
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DOR is defined as the duration of time from the date of initial response (CR or PR) to the date of progressive cGVHD or death, whichever occurs first.
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From the date of initial documentation of a response to the date of first documented evidence of progressive cGVHD or death, whichever occurs first (approximately up to 4.5 years)
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Percentage of Participants with cGVHD response at Each Timepoint of Efficacy Evaluation
Time Frame: Screening, Day 1 Weeks 1, 5, 13 and 25, Week 37 and every 12 weeks (q12w) thereafter, Progressive cGVHD Visit, End-of-Treatment and Response Follow-up Visits (until progressive cGVHD) q12w (approximately up to 4.5 years)
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Percentage of Participants with cGVHD response at each timepoint of efficacy evaluation (cGVHD response rate) is defined as percentage of participants with NIH defined CR or PR at each timepoint.
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Screening, Day 1 Weeks 1, 5, 13 and 25, Week 37 and every 12 weeks (q12w) thereafter, Progressive cGVHD Visit, End-of-Treatment and Response Follow-up Visits (until progressive cGVHD) q12w (approximately up to 4.5 years)
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Change in the Amount of Corticosteroid Required Per Participant Over Time
Time Frame: Screening, Day 1 Weeks 1, 2, 5, 9, 13, 17, 21, 25, Week 37 and q12w thereafter, Progressive cGVHD Visit, End-of-Treatment and Response Follow-up Visits (until progressive cGVHD) q12w (approximately up to 4.5 years)
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Change in the amount of corticosteroid required per participant over time will be monitored across the study.
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Screening, Day 1 Weeks 1, 2, 5, 9, 13, 17, 21, 25, Week 37 and q12w thereafter, Progressive cGVHD Visit, End-of-Treatment and Response Follow-up Visits (until progressive cGVHD) q12w (approximately up to 4.5 years)
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Improvement in Symptom Burden Measured by the Lee cGVHD Symptom Scale
Time Frame: Screening, Day 1 Weeks 1, 5, 13 and 25, Week 37 and q12w thereafter, Progressive cGVHD Visit, End-of-Treatment and Response Follow-up Visits (until progressive cGVHD) q12w (approximately up to 4.5 years)
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Lee cGVHD Symptom Scale is a participant-reported symptom scale.
It includes a total of 30 items within the following 7 domains: Skin, eyes and mouth, breathing, eating and digestion, muscles and joints, energy, mental and emotional for evaluating overall response.
Response options range from 0 to 4 and includes: "not at all" (0), "Slightly" (1), "Moderately" (2), "Quite a bit" (3), and "extremely" (4), and yield an overall score.
A change greater than or equal to (>=) 7 points on the Lee cGVHD Symptom Scale will be considered significant and relates to improvement in quality of life (QoL).
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Screening, Day 1 Weeks 1, 5, 13 and 25, Week 37 and q12w thereafter, Progressive cGVHD Visit, End-of-Treatment and Response Follow-up Visits (until progressive cGVHD) q12w (approximately up to 4.5 years)
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Number of Participants with Adverse Events (AEs) as a Measure of Safety
Time Frame: From signing Informed Consent Form until 30 days after the last dose of study treatment (approximately up to 4.5 years)
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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.
An AE can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non-investigational) product, whether or not related to that medicinal (investigational or non-investigational) product.
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From signing Informed Consent Form until 30 days after the last dose of study treatment (approximately up to 4.5 years)
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Number of Participants with Clinical Laboratory Abnormalities
Time Frame: Screening, Day 1 Weeks 1, 2, 5, 9, 13, 17, 21, 25, Week 37 and q12w thereafter, Progressive cGVHD Visit, End-of-Treatment (approximately up to 4.5 years)
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Number of participants with clinical laboratory abnormalities will be reported.
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Screening, Day 1 Weeks 1, 2, 5, 9, 13, 17, 21, 25, Week 37 and q12w thereafter, Progressive cGVHD Visit, End-of-Treatment (approximately up to 4.5 years)
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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 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
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AUC (0-last) is defined as the area under the plasma concentration-time curve from time zero to time of last measurable concentration.
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Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
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Area Under the Plasma Concentration-Time Curve from Time Zero to 24 Hours (AUC [0-24]) of Ibrutinib
Time Frame: Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
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AUC (0-24) is defined as the area under the plasma concentration-time curve from time zero to 24 hours.
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Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
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Maximum Observed Plasma Concentration (Cmax) of Ibrutinib
Time Frame: Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
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Cmax is defined as the maximum observed plasma concentration.
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Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
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Time to Reach Maximum Observed Plasma Concentration (Tmax) of Ibrutinib
Time Frame: Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
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Tmax is defined as actual sampling time to reach maximum observed plasma concentration.
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Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
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Elimination Half-Life (t1/2) of Ibrutinib
Time Frame: Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
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Elimination half-life (t1/2) is the time measured for the plasma concentration to decrease by 1 half to its original concentration.
It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).
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Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
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AUC (0-last) of Metabolite PCI-45227
Time Frame: Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
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AUC (0-last) is defined as the area under the plasma concentration-time curve from time zero to time of last measurable concentration.
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Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
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AUC (0-24) of Metabolite PCI-45227
Time Frame: Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
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AUC (0-24) is defined as the area under the plasma concentration-time curve from time zero to 24 hours.
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Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
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Cmax of Metabolite PCI-45227
Time Frame: Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
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Cmax is defined as the maximum observed plasma concentration.
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Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
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Tmax of Metabolite PCI-45227
Time Frame: Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
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Tmax is defined as actual sampling time to reach maximum observed plasma concentration.
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Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
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t1/2 of Metabolite PCI-45227
Time Frame: Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
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Elimination half-life (t1/2) is the time measured for the plasma concentration to decrease by 1 half to its original concentration.
It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).
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Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
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.
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)
May 1, 2018
Primary Completion (Actual)
November 29, 2021
Study Completion (Actual)
November 29, 2021
Study Registration Dates
First Submitted
March 16, 2018
First Submitted That Met QC Criteria
March 16, 2018
First Posted (Actual)
March 22, 2018
Study Record Updates
Last Update Posted (Actual)
January 3, 2022
Last Update Submitted That Met QC Criteria
December 30, 2021
Last Verified
December 1, 2021
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID 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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