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Graft vs Host DiseasePhase 3NCT03474679

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

A Phase 3 study testing Ibrutinib in people with Graft vs Host Disease, run by Janssen Pharmaceutical K.K. at 15 sites in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 12 years and older
Conditions the study is for
Graft vs Host Disease
What is being tested?
Ibrutinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
19 participants
Where
15 sitesJapan
Study dates
1 May 2018to 29 Nov 2021
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

15 sites in 1 country.

15 sites in 1 country

Japan15 sites
  • Anjo Kosei Hospital

    Anjo-shi, 446-8602

  • Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital

    Bunkyō City, 113 8677

  • Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital

    Hiroshima, 730-8619

  • Tokai University Hospital

    Isehara, 259-1193

  • Osaka Women's and Children's Hospital

    Izumi, 594-1101

  • Kobe City Medical Center General Hospital

    Kobe, 650 0047

  • National Hospital Organization Kumamoto Medical Center

    Kumamoto, 860-0008

  • Kurashiki Central Hospital

    Kurashiki, 710-8602

  • Gunmaken Saiseikai Maebashi Hospital

    Maebashi, 371-0821

  • Japanese Red Cross Nagoya Daiichi Hospital

    Nagoya, 453-8511

  • The Hospital of Hyogo College of Medicine

    Nishinomiya, 663-8501

  • Okayama University Hospital

    Okayama, 700 8558

  • Osaka City University Hospital

    Osaka, 545 8586

  • Hokkaido University Hospital

    Sapporo, 060-8648

  • National Center for Child Health and Development

    Setagaya Ku, 157 8535

Other trials in Japan

About this study

Official title: 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]).

Being tested
Ibrutinib
Medical subject headings
Graft vs Host Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IbrutinibDrug

    Also called PCI-32765, JNJ-54179060

    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.

Study groups in NCT03474679
Study groupRoleWhat they receive
IbrutinibExperimentalParticipants 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.
Receives: Drug: Ibrutinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 3 year 6 months

Secondary outcomes (22)
  1. 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.

    Measured: Up to 3 year 6 months

  2. 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.

    Measured: Up to 3 year 6 months

  3. 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.

    Measured: Weeks 5, 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157

  4. Change in the Amount of Corticosteroid Required Over Time

    Change in the amount of corticosteroid required over time was reported.

    Measured: Baseline, Weeks 24, 48, 96, and 144

  5. 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).

    Measured: Up to 3 year 6 months

  6. 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.

    Measured: Up to 3 year 6 months

  7. 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.

    Measured: Day 1 of Weeks 1 and 2

  8. 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.

    Measured: 0 to 24 hours (Day 1 of Weeks 1 and 2)

  9. Maximum Observed Plasma Concentration (Cmax) of Ibrutinib

    Cmax is defined as maximum observed plasma concentration of ibrutinib.

    Measured: Day 1 of Weeks 1 and 2

  10. Time to Reach Maximum Observed Plasma Concentration (Tmax) of Ibrutinib

    Tmax is defined as time to reach the maximum observed plasma concentration of ibrutinib.

    Measured: Day 1 of Weeks 1 and 2

  11. Elimination Half-Life (t1/2) of Ibrutinib

    T1/2 is defined as elimination half-life of ibrutinib.

    Measured: Day 1 of Weeks 1 and 2

  12. Apparent Clearance (CL/F) of Ibrutinib

    CL/F is defined as apparent clearance of ibrutinib.

    Measured: Day 1 of Weeks 1 and 2

  13. Apparent Volume of Distribution (Vd/F) of Ibrutinib

    Vd/F is defined as apparent volume of distribution of ibrutinib.

    Measured: Day 1 of Weeks 1 and 2

  14. 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.

    Measured: Day 1 of Weeks 1 and 2

  15. 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.

    Measured: Day 1 of Weeks 1 and 2

  16. 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.

    Measured: 0 to 24 hours (Day 1 of Weeks 1 and 2)

  17. Maximum Observed Plasma Concentration (Cmax) of PCI-45227

    Cmax is defined as maximum observed plasma concentration of PCI-45227.

    Measured: Day 1 of Weeks 1 and 2

  18. 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.

    Measured: Day 1 of Weeks 1 and 2

  19. Elimination Half-Life (t1/2) of PCI-45227

    T1/2 is defined as elimination half-life of PCI-45227.

    Measured: Day 1 of Weeks 1 and 2

  20. Apparent Clearance (CL/F) of PCI-45227

    CL/F is defined as apparent clearance of PCI-45227.

    Measured: Day 1 of Weeks 1 and 2

  21. Apparent Volume of Distribution (Vd/F) of PCI-45227

    Vd/F is defined as apparent volume of distribution of PCI-45227.

    Measured: Day 1 of Weeks 1 and 2

  22. 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.

    Measured: Day 1 of Weeks 1 and 2

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Mar 2018
  2. Study start1 May 2018
  3. Primary completion29 Nov 2021
  4. Study completion29 Nov 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
19 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03474679
Sponsor's protocol ID
CR108443
Other IDs
54179060GVH3001
Status last verified
Jan 2025
First submitted
16 Mar 2018
Last updated
4 Feb 2025
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Toyosaki M, Doki N, Shiratori S, Osumi T, Okada M, Kawakita T, Sawa M, Ishikawa T, Ueda Y, Hatayama T, Yoshinari N, Fujikawa E. Long-term Use of Ibrutinib in Japanese Patients with Steroid Dependent/Refractory cGVHD: Final Analysis of Multicenter Study. Blood Cell Ther. 2023 Nov 10;6(4):104-113. doi: 10.31547/bct-2023-010. eCollection 2023 Nov 25.

    PubMed 38149026
  • Doki N, Toyosaki M, Shiratori S, Osumi T, Okada M, Kawakita T, Sawa M, Ishikawa T, Ueda Y, Yoshinari N, Nakahara S. An Open-Label, Single-Arm, Multicenter Study of Ibrutinib in Japanese Patients With Steroid-dependent/Refractory Chronic Graft-Versus-Host Disease. Transplant Cell Ther. 2021 Oct;27(10):867.e1-867.e9. doi: 10.1016/j.jtct.2021.05.019. Epub 2021 Jun 6.

    PubMed 34102349

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ibrutinib in people with Graft vs Host Disease, run by Janssen Pharmaceutical K.K. at 15 sites in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response Rate (ORR) (time frame: Up to 3 year 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03474679, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Feb 2025.

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