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

NCT ID: NCT03474679

Last Updated: 2025-02-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-05-01
• Study Completion Date: 2021-11-29

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]).

Conditions

Graft vs Host Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Ibrutinib

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

PCI-32765; JNJ-54179060

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

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Pharmaceutical K.K.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Pharmaceutical K.K., Japan Clinical Trial

Role: STUDY_DIRECTOR

Janssen Pharmaceutical K.K.

Locations

Anjo Kosei Hospital

Anjo-shi, , Japan

Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital

Bunkyō City, , Japan

Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital

Hiroshima, , Japan

Tokai University Hospital

Isehara, , Japan

Osaka Women's and Children's Hospital

Izumi, , Japan

Kobe City Medical Center General Hospital

Kobe, , Japan

National Hospital Organization Kumamoto Medical Center

Kumamoto, , Japan

Kurashiki Central Hospital

Kurashiki, , Japan

Gunmaken Saiseikai Maebashi Hospital

Maebashi, , Japan

Japanese Red Cross Nagoya Daiichi Hospital

Nagoya, , Japan

The Hospital of Hyogo College of Medicine

Nishinomiya, , Japan

Okayama University Hospital

Okayama, , Japan

Osaka City University Hospital

Osaka, , Japan

Hokkaido University Hospital

Sapporo, , Japan

National Center for Child Health and Development

Setagaya Ku, , Japan

Countries

Japan

References

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.

Reference Type: DERIVED

PMID: 38149026 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34102349 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

54179060GVH3001

Identifier Type: OTHER

Identifier Source: secondary_id

CR108443

Identifier Type: -

Identifier Source: org_study_id