Back to resultsStudy of the Bruton's Tyrosine Kinase Inhibitor in Subjects With Chronic Graft Versus Host Disease
Primary Purpose
Graft Versus Host Disease
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Ibrutinib
Sponsored by
About this trial
This is an interventional treatment trial for Graft Versus Host Disease focused on measuring PCYC1129, PCYC1129CA, 1129, Ibrutinib, PCI32765, IMBRUVICA, Pharmacyclics, PCYC, GVHD, Steroid dependent, refractory, chronic, graft versus host disease, chronic graft versus host disease, immunology
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.
Sites / Locations
- City of Hope Medical Center
- University of California, San Francisco
- Stanford University
- Emory University, Winship Cancer Institute
- Dana Farber Cancer Institute
- University of Minnesota
- Washington University School of Medicine
- Ohio State University Comprehensive Cancer Center
- Vanderbilt University Medical Center, Henry-Joyce Cancer Clinic
- Fred Hutchinson Cancer Research Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Phase 1b: Dose Level 1
Phase 1b: Dose Level 2
Phase 1b: Dose Level 3
Phase 2
Arm Description
Subjects receive daily dose of 420 mg of Ibrutinib capsules
Subjects receive daily dose of 280 mg of Ibrutinib capsules
Subjects receive daily dose of 140 mg of Ibrutinib capsules
Subjects receive daily dose of recommended phase 2 dose
Outcomes
Primary Outcome Measures
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
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).
Secondary Outcome Measures
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.
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.
Corticosteroid Requirement Changes Over Time
Average daily corticosteroid dose assessed each week.
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.
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02195869
Brief Title
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
2. Study Status
Record Verification Date
June 2019
Overall Recruitment Status
Completed
Study Start Date
July 14, 2014 (Actual)
Primary Completion Date
September 15, 2017 (Actual)
Study Completion Date
September 15, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pharmacyclics LLC.
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
45 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Phase 1b: Dose Level 1
Arm Type
Experimental
Arm Description
Subjects receive daily dose of 420 mg of Ibrutinib capsules
Arm Title
Phase 1b: Dose Level 2
Arm Type
Experimental
Arm Description
Subjects receive daily dose of 280 mg of Ibrutinib capsules
Arm Title
Phase 1b: Dose Level 3
Arm Type
Experimental
Arm Description
Subjects receive daily dose of 140 mg of Ibrutinib capsules
Arm Title
Phase 2
Arm Type
Experimental
Arm Description
Subjects receive daily dose of recommended phase 2 dose
Intervention Type
Drug
Intervention Name(s)
Ibrutinib
Other Intervention Name(s)
PCI32765
Primary Outcome Measure Information:
Title
Phase 1b: To Evaluate the Safety and Tolerability of Ibrutinib in Steroid Dependent/Refractory cGVHD.
Description
Number of participants with dose-limiting toxicities as a measure of safety profile to determine recommended dose of ibrutinib
Time Frame
28 treatment days after last subject enrolled in Phase 1 dose level(s).
Title
Phase 2: Overall Response Rate as the Percentage of Participants With Response
Description
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).
Time Frame
Analysis was conducted with the data extraction date of 15 Sep 2017, with a median follow-up time of 25.56 months.
Secondary Outcome Measure Information:
Title
Sustained Response Rate as the Percentage of Participants With Sustained Response
Description
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.
Time Frame
Analysis was conducted with the data extraction date of 15 Sep 2017, with a median follow-up time of 25.56 months.
Title
To Evaluate the Clinical Efficacy of Ibrutinib in Steroid Dependent/Refractory cGVHD by Measuring: Duration of Response (DOR)
Description
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.
Time Frame
Analysis was conducted with the data extraction date of 15 Sep 2017, with a median follow-up time of 25.56 months.
Title
Corticosteroid Requirement Changes Over Time
Description
Average daily corticosteroid dose assessed each week.
Time Frame
Analysis was conducted with the data extraction date of 15 Sep 2017, with a median follow-up time of 25.56 months.
Title
Percentage of Participants With Overall Improvement in Lee cGVHD Symptom Summary Score
Description
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.
Time Frame
Analysis was conducted with the data extraction date of 15 Sep 2017, with a median follow-up time of 25.56 months.
Title
Phase 2b: To Evaluate the Safety and Tolerability of Ibrutinib in Steroid Dependent/Refractory cGVHD
Description
Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Ibrutinib
Time Frame
From first dose with study drug until 30 days after the last dose of study drug, up to 36.7 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lori Styles, MD
Organizational Affiliation
Pharmacyclics LLC.
Official's Role
Study Director
Facility Information:
Facility Name
City of Hope Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
University of California, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Stanford University
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Emory University, Winship Cancer Institute
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Ohio State University Comprehensive Cancer Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Vanderbilt University Medical Center, Henry-Joyce Cancer Clinic
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Fred Hutchinson Cancer Research Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
34102349
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.
Results Reference
derived
PubMed Identifier
31260802
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.
Results Reference
derived
PubMed Identifier
28924018
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.
Results Reference
derived
Learn more about this trial
Study of the Bruton's Tyrosine Kinase Inhibitor in Subjects With Chronic Graft Versus Host Disease
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