Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02195869
Recruitment Status : Completed
First Posted : July 21, 2014
Results First Posted : July 11, 2019
Last Update Posted : July 11, 2019
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Graft Versus Host Disease Drug: Ibrutinib Phase 1 Phase 2

Layout table for study information
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
Drug: Ibrutinib
Other Name: PCI32765

Experimental: Phase 1b: Dose Level 2
Subjects receive daily dose of 280 mg of Ibrutinib capsules
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
Drug: Ibrutinib
Other Name: PCI32765




Primary Outcome Measures :
  1. 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

  2. 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).


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.


  5. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Information from the National Library of Medicine

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


Locations
Layout table for location information
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
Sponsors and Collaborators
Pharmacyclics LLC.
Investigators
Layout table for investigator information
Study Director: Lori Styles, MD Pharmacyclics LLC.
  Study Documents (Full-Text)

Documents provided by Pharmacyclics LLC.:
Study Protocol  [PDF] October 21, 2015
Statistical Analysis Plan  [PDF] August 31, 2016

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
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
Keywords provided by Pharmacyclics LLC.:
PCYC1129
PCYC1129CA
1129
Ibrutinib
PCI32765
IMBRUVICA
Pharmacyclics
PCYC
GVHD
Steroid dependent
refractory
chronic
graft versus host disease
chronic graft versus host disease
immunology
Additional relevant MeSH terms:
Layout table for MeSH terms
Graft vs Host Disease
Immune System Diseases