Study of the Bruton's Tyrosine Kinase Inhibitor in Subjects With Chronic Graft Versus Host Disease

Graft Versus Host Disease Clinical Trial

Official title:

A Multicenter Open-Label Phase 1b/2 Study of Ibrutinib in Steroid Dependent or Refractory Chronic Graft Versus Host Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02195869
• Other study ID #: PCYC-1129-CA
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: July 14, 2014
• Est. completion date: September 15, 2017

Study information

• Verified date: June 2019
• Source: Pharmacyclics LLC.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: September 15, 2017
• Est. primary completion date: September 15, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Graft Versus Host Disease
• Graft vs Host Disease

Intervention

Drug:
• Ibrutinib

Locations

Country	Name	City	State
United States	Emory University, Winship Cancer Institute	Atlanta	Georgia
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	City of Hope Medical Center	Duarte	California
United States	University of Minnesota	Minneapolis	Minnesota
United States	Vanderbilt University Medical Center, Henry-Joyce Cancer Clinic	Nashville	Tennessee
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	University of California, San Francisco	San Francisco	California
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Stanford University	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Pharmacyclics LLC.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1b: To Evaluate the Safety and Tolerability of Ibrutinib in Steroid Dependent/Refractory cGVHD.	Number of participants with dose-limiting toxicities as a measure of safety profile to determine recommended dose of ibrutinib	28 treatment days after last subject enrolled in Phase 1 dose level(s).
Primary	Phase 2: Overall Response Rate as the Percentage of Participants With Response	Overall Response Rate is defined as the proportion of subjects who achieved complete response (CR) or partial response (PR). Response criteria are based on NIH cGVHD Response assessment (Pavletic 2006; Measurement of Therapeutic Response, ASBMT Web site).	Analysis was conducted with the data extraction date of 15 Sep 2017, with a median follow-up time of 25.56 months.
Secondary	Sustained Response Rate as the Percentage of Participants With Sustained Response	For subjects who achieved an NIH-defined CR or PR, the proportion of subjects who achieved CR or PR that was sustained for at least 20 weeks (140 days). Intermittent SD was also acceptable.	Analysis was conducted with the data extraction date of 15 Sep 2017, with a median follow-up time of 25.56 months.
Secondary	To Evaluate the Clinical Efficacy of Ibrutinib in Steroid Dependent/Refractory cGVHD by Measuring: Duration of Response (DOR)	For subjects who achieved an NIH-defined CR or PR, the interval between the date of initial documentation of a response and the date of first documented evidence of PD, death, or date of censoring if applicable.	Analysis was conducted with the data extraction date of 15 Sep 2017, with a median follow-up time of 25.56 months.
Secondary	Corticosteroid Requirement Changes Over Time	Average daily corticosteroid dose assessed each week.	Analysis was conducted with the data extraction date of 15 Sep 2017, with a median follow-up time of 25.56 months.
Secondary	Percentage of Participants With Overall Improvement in Lee cGVHD Symptom Summary Score	Subject reported improvement in symptom burden. The symptom burden will be measured according to the Lee cGVHD Symptom Scale. A change in >7 points on the Lee cGVHD Symptom Scale will be considered significant and relates to improvement in quality of life.; A score is 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 scale. A total summary score is calculated as the average of these 7 subscales if at least 4 subscales have valid scores.; There are 7 subscales (Skin, Energy, Lung, Eye, Nutrition, Mouth and Psychological) with ratings as follow: 0- Not at all, 1- Slightly, 2 Moderately, 3 Quite a bit, 4-Extremely; with a lower values representing a better outcome.	Analysis was conducted with the data extraction date of 15 Sep 2017, with a median follow-up time of 25.56 months.
Secondary	Phase 2b: To Evaluate the Safety and Tolerability of Ibrutinib in Steroid Dependent/Refractory cGVHD	Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Ibrutinib	From first dose with study drug until 30 days after the last dose of study drug, up to 36.7 months