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)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Graft vs Host Disease
Lead sponsor: Janssen Pharmaceutical K.K.
Sponsor class: INDUSTRY
First posted: 2018-03-22
Enrollment: 19
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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 project criteria \[2014\]).


Eligibility criteria: 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

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Up to 3 year 6 months
Secondary outcomes:
measure: Sustained Response Rate
timeFrame: Up to 3 year 6 months
measure: Duration of Response (DOR)
timeFrame: Up to 3 year 6 months
measure: cGVHD Response Rate at Each Timepoints
timeFrame: Weeks 5, 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157
measure: Change in the Amount of Corticosteroid Required Over Time
timeFrame: Baseline, Weeks 24, 48, 96, and 144
measure: Percentage of Participants With Overall Improvement in Lee cGVHD Symptom Scale Score
timeFrame: Up to 3 year 6 months
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to 3 year 6 months
measure: Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (AUC [0-last]) of Ibrutinib
timeFrame: Day 1 of Weeks 1 and 2
measure: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC [0-24]) of Ibrutinib
timeFrame: 0 to 24 hours (Day 1 of Weeks 1 and 2)
measure: Maximum Observed Plasma Concentration (Cmax) of Ibrutinib
timeFrame: Day 1 of Weeks 1 and 2
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Ibrutinib
timeFrame: Day 1 of Weeks 1 and 2
measure: Elimination Half-Life (t1/2) of Ibrutinib
timeFrame: Day 1 of Weeks 1 and 2
measure: Apparent Clearance (CL/F) of Ibrutinib
timeFrame: Day 1 of Weeks 1 and 2
measure: Apparent Volume of Distribution (Vd/F) of Ibrutinib
timeFrame: Day 1 of Weeks 1 and 2
measure: Area Under the Plasma Concentration-time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Ibrutinib
timeFrame: Day 1 of Weeks 1 and 2
measure: Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (AUC [0-last]) of PCI-45227
timeFrame: Day 1 of Weeks 1 and 2
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC [0-24]) of PCI-45227
timeFrame: 0 to 24 hours (Day 1 of Weeks 1 and 2)
measure: Maximum Observed Plasma Concentration (Cmax) of PCI-45227
timeFrame: Day 1 of Weeks 1 and 2
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PCI-45227
timeFrame: Day 1 of Weeks 1 and 2
measure: Elimination Half-Life (t1/2) of PCI-45227
timeFrame: Day 1 of Weeks 1 and 2
measure: Apparent Clearance (CL/F) of PCI-45227
timeFrame: Day 1 of Weeks 1 and 2
measure: Apparent Volume of Distribution (Vd/F) of PCI-45227
timeFrame: Day 1 of Weeks 1 and 2
measure: Area Under the Plasma Concentration-time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of PCI-45227
timeFrame: Day 1 of Weeks 1 and 2
Other outcomes:
Locations:
city: Anjo-shi
country: Japan
facility: Anjo Kosei Hospital
city: Bunkyo ku
country: Japan
facility: Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital
city: Hiroshima
country: Japan
facility: Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital
city: Isehara
country: Japan
facility: Tokai University Hospital
city: Izumi
country: Japan
facility: Osaka Women's and Children's Hospital
city: Kobe City
country: Japan
facility: Kobe City Medical Center General Hospital
city: Kumamoto-shi
country: Japan
facility: National Hospital Organization Kumamoto Medical Center
city: Kurashiki
country: Japan
facility: Kurashiki Central Hospital
city: Maebashi
country: Japan
facility: Gunmaken Saiseikai Maebashi Hospital
city: Nagoya
country: Japan
facility: Japanese Red Cross Nagoya Daiichi Hospital
city: Nishinomiya
country: Japan
facility: The Hospital of Hyogo College of Medicine
city: Okayama
country: Japan
facility: Okayama University Hospital
city: Osaka
country: Japan
facility: Osaka City University Hospital
city: Sapporo-shi
country: Japan
facility: Hokkaido University Hospital
city: Setagaya Ku
country: Japan
facility: National Center for Child Health and Development
Study officials:
affiliation: Janssen Pharmaceutical K.K.
name: Janssen Pharmaceutical K.K., Japan Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.