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

NCT03474679 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: CR10844354179060GVH3001
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 15

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

Outcome Measures

Primary Outcomes (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.

  Up to 3 year 6 months

Secondary Outcomes (22)

• Sustained Response Rate

  Up to 3 year 6 months

• Duration of Response (DOR)

  Up to 3 year 6 months

• cGVHD Response Rate at Each Timepoints

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

• Change in the Amount of Corticosteroid Required Over Time

  Baseline, Weeks 24, 48, 96, and 144

• Percentage of Participants With Overall Improvement in Lee cGVHD Symptom Scale Score

  Up to 3 year 6 months

Study Arms (1)

Ibrutinib

EXPERIMENTAL

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

Interventions

Ibrutinib 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.

Also known as: PCI-32765, JNJ-54179060

Ibrutinib

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Pharmaceutical K.K.: lead

Study Sites (15)

Anjo Kosei Hospital

Anjo-shi, 446-8602, Japan

Location

Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital

Bunkyō City, 113 8677, Japan

Location

Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital

Hiroshima, 730-8619, Japan

Location

Tokai University Hospital

Isehara, 259-1193, Japan

Location

Osaka Women's and Children's Hospital

Izumi, 594-1101, Japan

Location

Kobe City Medical Center General Hospital

Kobe, 650 0047, Japan

Location

National Hospital Organization Kumamoto Medical Center

Kumamoto, 860-0008, Japan

Location

Kurashiki Central Hospital

Kurashiki, 710-8602, Japan

Location

Gunmaken Saiseikai Maebashi Hospital

Maebashi, 371-0821, Japan

Location

Japanese Red Cross Nagoya Daiichi Hospital

Nagoya, 453-8511, Japan

Location

The Hospital of Hyogo College of Medicine

Nishinomiya, 663-8501, Japan

Location

Okayama University Hospital

Okayama, 700 8558, Japan

Location

Osaka City University Hospital

Osaka, 545 8586, Japan

Location

Hokkaido University Hospital

Sapporo, 060-8648, Japan

Location

National Center for Child Health and Development

Setagaya Ku, 157 8535, Japan

Location

Related Publications (2)

• 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.

  PMID: 38149026 DERIVED

• 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.

  PMID: 34102349 DERIVED

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

ibrutinib

Condition Hierarchy (Ancestors)

Immune System Diseases

Results Point of Contact

• Title: EXECUTIVE MEDICAL DIRECTOR
• Organization: Janssen Pharmaceutical K.K.

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen Pharmaceutical K.K., Japan Clinical Trial

  Janssen Pharmaceutical K.K.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2018
• First Posted: March 22, 2018
• Study Start: May 1, 2018
• Primary Completion: November 29, 2021
• Study Completion: November 29, 2021
• Last Updated: February 4, 2025
• Results First Posted: February 3, 2023

Record last verified: 2025-01

Locations

JP (15)