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

Phase 1

Completed

• Conditions: Graft Versus Host Disease
• Interventions: Drug: Ibrutinib

• Registration Number: NCT02195869
• Lead Sponsor: Pharmacyclics LLC.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-07-11
• Study Start: 2014-07-14
• Study First Submitted QC: 2014-07-16
• Study First Posted: 2014-07-21
• Primary Completion: 2017-09-15
• Study Completion: 2017-09-15
• Results First Submitted: 2019-04-30
• Status Verified: 2019-06
• Results First Submitted QC: 2019-06-14
• Last Update Submitted: 2019-06-14
• Results First Posted: 2019-07-11
• Last Update Posted: 2019-07-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 45

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Phase 1b: Dose Level 1	Ibrutinib	Subjects receive daily dose of 420 mg of Ibrutinib capsules
Phase 2	Ibrutinib	Subjects receive daily dose of recommended phase 2 dose
Phase 1b: Dose Level 3	Ibrutinib	Subjects receive daily dose of 140 mg of Ibrutinib capsules
Phase 1b: Dose Level 2	Ibrutinib	Subjects receive daily dose of 280 mg of Ibrutinib capsules

Primary Outcome Measures

Name	Time	Method
Phase 2: Overall Response Rate as the Percentage of Participants With Response	Analysis was conducted with the data extraction date of 15 Sep 2017, with a median follow-up time of 25.56 months.	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).
Phase 1b: To Evaluate the Safety and Tolerability of Ibrutinib in Steroid Dependent/Refractory cGVHD.	28 treatment days after last subject enrolled in Phase 1 dose level(s).	Number of participants with dose-limiting toxicities as a measure of safety profile to determine recommended dose of ibrutinib

Secondary Outcome Measures

Name	Time	Method
To Evaluate the Clinical Efficacy of Ibrutinib in Steroid Dependent/Refractory cGVHD by Measuring: Duration of Response (DOR)	Analysis was conducted with the data extraction date of 15 Sep 2017, with a median follow-up time of 25.56 months.	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.
Corticosteroid Requirement Changes Over Time	Analysis was conducted with the data extraction date of 15 Sep 2017, with a median follow-up time of 25.56 months.	Average daily corticosteroid dose assessed each week.
Phase 2b: To Evaluate the Safety and Tolerability of Ibrutinib in Steroid Dependent/Refractory cGVHD	From first dose with study drug until 30 days after the last dose of study drug, up to 36.7 months	Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Ibrutinib
Percentage of Participants With Overall Improvement in Lee cGVHD Symptom Summary Score	Analysis was conducted with the data extraction date of 15 Sep 2017, with a median follow-up time of 25.56 months.	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.
Sustained Response Rate as the Percentage of Participants With Sustained Response	Analysis was conducted with the data extraction date of 15 Sep 2017, with a median follow-up time of 25.56 months.	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.

Trial Locations

Locations (10)

University of California, San Francisco; 🇺🇸 San Francisco, California, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

Dana Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Emory University, Winship Cancer Institute; 🇺🇸 Atlanta, Georgia, United States

City of Hope Medical Center; 🇺🇸 Duarte, California, United States

Vanderbilt University Medical Center, Henry-Joyce Cancer Clinic; 🇺🇸 Nashville, Tennessee, United States

University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States

Ohio State University Comprehensive Cancer Center; 🇺🇸 Columbus, Ohio, United States

Stanford University; 🇺🇸 Stanford, California, United States

Fred Hutchinson Cancer Research Center; 🇺🇸 Seattle, Washington, United States