Clinical trial NCT02195869: Study of the Bruton's Tyrosine Kinase Inhibitor in Subjects With Chronic Graft Versus Host Disease
Official title: A Multicenter Open-Label Phase 1b/2 Study of Ibrutinib in Steroid Dependent or Refractory Chronic Graft Versus Host Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Graft Versus Host Disease
Keywords: PCYC1129
PCYC1129CA
1129
Ibrutinib
PCI32765
IMBRUVICA
Pharmacyclics
PCYC
GVHD
Steroid dependent
refractory
chronic
graft versus host disease
chronic graft versus host disease
immunology
Lead sponsor: Pharmacyclics LLC.
Sponsor class: INDUSTRY
First posted: 2014-07-21
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the safety and clinical efficacy of ibrutinib in subjects with steroid dependent or refractory Chronic Graft Versus Host Disease.


Eligibility criteria: Inclusion Criteria:

* Steroid dependent or refractory classic chronic GVHD disease.
* No more than 3 previous treatments for cGVHD.
* Receiving baseline systemic glucocorticoid therapy (at stable dose) for cGVHD at study entry.
* Men and women ≥18 years old.
* Karnofsky performance status ≥60.

Exclusion Criteria:

* Known or suspected active acute GVHD.
* Current treatment with sirolimus AND either cyclosporine or tacrolimus.
* History of treatment with a tyrosine kinase inhibitor (eg, imatinib), purine analogs or other cancer chemotherapy in the 4 weeks prior to starting study drug.
* Currently active, clinically significant cardiovascular disease.
* Uncontrolled infections not responsive to antibiotics, antiviral medicines, or antifungal medicines or a recent infection requiring systemic treatment that was completed ≤14 days before the first dose of study drug.
* Progressive underlying malignant disease including post-transplant lymphoproliferative disease.
* History of other malignancy (not including the underlying malignancy that was the indication for transplant)
* Concomitant use of warfarin or other Vitamin K antagonists
* Known bleeding disorders or hemophilia.
* History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
* Known history of human immunodeficiency virus (HIV) or active with hepatitis C virus (HCV) or hepatitis B virus (HBV).
* Concurrent use of a strong cytochrome P450(CYP) 3A inhibitor.

Primary outcomes:
measure: Phase 1b: To Evaluate the Safety and Tolerability of Ibrutinib in Steroid Dependent/Refractory cGVHD.
timeFrame: 28 treatment days after last subject enrolled in Phase 1 dose level(s).
measure: Phase 2: Overall Response Rate as the Percentage of Participants With Response
timeFrame: Analysis was conducted with the data extraction date of 15 Sep 2017, with a median follow-up time of 25.56 months.
Secondary outcomes:
measure: Sustained Response Rate as the Percentage of Participants With Sustained Response
timeFrame: Analysis was conducted with the data extraction date of 15 Sep 2017, with a median follow-up time of 25.56 months.
measure: To Evaluate the Clinical Efficacy of Ibrutinib in Steroid Dependent/Refractory cGVHD by Measuring: Duration of Response (DOR)
timeFrame: Analysis was conducted with the data extraction date of 15 Sep 2017, with a median follow-up time of 25.56 months.
measure: Corticosteroid Requirement Changes Over Time
timeFrame: Analysis was conducted with the data extraction date of 15 Sep 2017, with a median follow-up time of 25.56 months.
measure: Percentage of Participants With Overall Improvement in Lee cGVHD Symptom Summary Score
timeFrame: Analysis was conducted with the data extraction date of 15 Sep 2017, with a median follow-up time of 25.56 months.
measure: Phase 2b: To Evaluate the Safety and Tolerability of Ibrutinib in Steroid Dependent/Refractory cGVHD
timeFrame: From first dose with study drug until 30 days after the last dose of study drug, up to 36.7 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Medical Center
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Atlanta
country: United States
facility: Emory University, Winship Cancer Institute
state: Georgia
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
city: Nashville
country: United States
facility: Vanderbilt University Medical Center, Henry-Joyce Cancer Clinic
state: Tennessee
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
Study officials:
affiliation: Pharmacyclics LLC.
name: Lori Styles, MD
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.
citation: Waller EK, Miklos D, Cutler C, Arora M, Jagasia MH, Pusic I, Flowers MED, Logan AC, Nakamura R, Chang S, Clow F, Lal ID, Styles L, Jaglowski S. Ibrutinib for Chronic Graft-versus-Host Disease After Failure of Prior Therapy: 1-Year Update of a Phase 1b/2 Study. Biol Blood Marrow Transplant. 2019 Oct;25(10):2002-2007. doi: 10.1016/j.bbmt.2019.06.023. Epub 2019 Jun 28.
citation: Miklos D, Cutler CS, Arora M, Waller EK, Jagasia M, Pusic I, Flowers ME, Logan AC, Nakamura R, Blazar BR, Li Y, Chang S, Lal I, Dubovsky J, James DF, Styles L, Jaglowski S. Ibrutinib for chronic graft-versus-host disease after failure of prior therapy. Blood. 2017 Nov 23;130(21):2243-2250. doi: 10.1182/blood-2017-07-793786. Epub 2017 Sep 18.