Study of the Bruton's Tyrosine Kinase Inhibitor in Subjects With Chronic Graft Versus Host Disease
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ClinicalTrials.gov Identifier: NCT02195869 |
Recruitment Status :
Completed
First Posted : July 21, 2014
Results First Posted : July 11, 2019
Last Update Posted : July 11, 2019
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Condition or disease | Intervention/treatment | Phase |
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Graft Versus Host Disease | Drug: Ibrutinib | Phase 1 Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 45 participants |
Allocation: | Non-Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Multicenter Open-Label Phase 1b/2 Study of Ibrutinib in Steroid Dependent or Refractory Chronic Graft Versus Host Disease |
Actual Study Start Date : | July 14, 2014 |
Actual Primary Completion Date : | September 15, 2017 |
Actual Study Completion Date : | September 15, 2017 |

Arm | Intervention/treatment |
---|---|
Experimental: Phase 1b: Dose Level 1
Subjects receive daily dose of 420 mg of Ibrutinib capsules
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Drug: Ibrutinib
Other Name: PCI32765 |
Experimental: Phase 1b: Dose Level 2
Subjects receive daily dose of 280 mg of Ibrutinib capsules
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Drug: Ibrutinib
Other Name: PCI32765 |
Experimental: Phase 1b: Dose Level 3
Subjects receive daily dose of 140 mg of Ibrutinib capsules
|
Drug: Ibrutinib
Other Name: PCI32765 |
Experimental: Phase 2
Subjects receive daily dose of recommended phase 2 dose
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Drug: Ibrutinib
Other Name: PCI32765 |
- Phase 1b: To Evaluate the Safety and Tolerability of Ibrutinib in Steroid Dependent/Refractory cGVHD. [ Time Frame: 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
- Phase 2: Overall Response Rate as the Percentage of Participants With Response [ Time Frame: 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).
- Sustained Response Rate as the Percentage of Participants With Sustained Response [ Time Frame: 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.
- To Evaluate the Clinical Efficacy of Ibrutinib in Steroid Dependent/Refractory cGVHD by Measuring: Duration of Response (DOR) [ Time Frame: 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 [ Time Frame: 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.
- Percentage of Participants With Overall Improvement in Lee cGVHD Symptom Summary Score [ Time Frame: 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.
- Phase 2b: To Evaluate the Safety and Tolerability of Ibrutinib in Steroid Dependent/Refractory cGVHD [ Time Frame: 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

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02195869
United States, California | |
City of Hope Medical Center | |
Duarte, California, United States, 91010 | |
University of California, San Francisco | |
San Francisco, California, United States, 94143 | |
Stanford University | |
Stanford, California, United States, 94305 | |
United States, Georgia | |
Emory University, Winship Cancer Institute | |
Atlanta, Georgia, United States, 30322 | |
United States, Massachusetts | |
Dana Farber Cancer Institute | |
Boston, Massachusetts, United States, 02215 | |
United States, Minnesota | |
University of Minnesota | |
Minneapolis, Minnesota, United States, 55455 | |
United States, Missouri | |
Washington University School of Medicine | |
Saint Louis, Missouri, United States, 63110 | |
United States, Ohio | |
Ohio State University Comprehensive Cancer Center | |
Columbus, Ohio, United States, 43210 | |
United States, Tennessee | |
Vanderbilt University Medical Center, Henry-Joyce Cancer Clinic | |
Nashville, Tennessee, United States, 37232 | |
United States, Washington | |
Fred Hutchinson Cancer Research Center | |
Seattle, Washington, United States, 98109 |
Study Director: | Lori Styles, MD | Pharmacyclics LLC. |
Documents provided by Pharmacyclics LLC.:
Responsible Party: | Pharmacyclics LLC. |
ClinicalTrials.gov Identifier: | NCT02195869 |
Other Study ID Numbers: |
PCYC-1129-CA |
First Posted: | July 21, 2014 Key Record Dates |
Results First Posted: | July 11, 2019 |
Last Update Posted: | July 11, 2019 |
Last Verified: | June 2019 |
PCYC1129 PCYC1129CA graft versus host disease chronic graft versus host disease 1129 Ibrutinib PCI32765 IMBRUVICA |
Pharmacyclics PCYC GVHD Steroid dependent refractory chronic immunology |
Graft vs Host Disease Immune System Diseases |