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Trial record 1 of 1 for:    PCYC-1129 | Graft-versus-host-disease
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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
Sponsor:
Information provided by (Responsible Party):
Pharmacyclics LLC.

Tracking Information
First Submitted Date  ICMJE July 11, 2014
First Posted Date  ICMJE July 21, 2014
Results First Submitted Date  ICMJE April 30, 2019
Results First Posted Date  ICMJE July 11, 2019
Last Update Posted Date July 11, 2019
Actual Study Start Date  ICMJE July 14, 2014
Actual Primary Completion Date September 15, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 14, 2019)
  • 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).
Original Primary Outcome Measures  ICMJE
 (submitted: July 16, 2014)
  • Phase 1b: Number of 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). ]
  • Phase 2 (Efficacy): Overall cGVHD response rate defined as the proportion of evaluable subjects who achieve a [NIH-defined Complete Response (CR) and Partial Response (PR)] over all subjects who were treated with RP2D [ Time Frame: When the last subject completes 6 months of treatment. ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 14, 2019)
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: July 16, 2014)
  • Failure Free Survival (FFS) [ Time Frame: When the last subject completes 6 and 12 months of treatment. ]
  • Change in symptom burden by the Lee cGVHD Symptom Scale [ Time Frame: Approximately 18 months after last subject is enrolled or up to disease progression, whichever occurs first. ]
  • Corticosteroid requirement changes over Time [ Time Frame: Approximately 18 months after last subject is enrolled or up to disease progression, whichever occurs first. ]
  • Number of subjects with Adverse Events (AE) as a measure of safety and tolerability of ibrutinib [ Time Frame: Approximately 18 months after last subject is enrolled. ]
  • Determine the plasma pharmacokinetics of ibrutinib and the metabolite, PCI-45227 [ Time Frame: Samples will be collected during the first two weeks of subject receiving study drug and will be assessed approximately 1 month after completion of the PK sample collections of the last subject enrolled at each dose level. ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of the Bruton's Tyrosine Kinase Inhibitor in Subjects With Chronic Graft Versus Host Disease
Official Title  ICMJE A Multicenter Open-Label Phase 1b/2 Study of Ibrutinib in Steroid Dependent or Refractory Chronic Graft Versus Host Disease
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Graft Versus Host Disease
Intervention  ICMJE Drug: Ibrutinib
Other Name: PCI32765
Study Arms  ICMJE
  • Experimental: Phase 1b: Dose Level 1
    Subjects receive daily dose of 420 mg of Ibrutinib capsules
    Intervention: Drug: Ibrutinib
  • Experimental: Phase 1b: Dose Level 2
    Subjects receive daily dose of 280 mg of Ibrutinib capsules
    Intervention: Drug: Ibrutinib
  • Experimental: Phase 1b: Dose Level 3
    Subjects receive daily dose of 140 mg of Ibrutinib capsules
    Intervention: Drug: Ibrutinib
  • Experimental: Phase 2
    Subjects receive daily dose of recommended phase 2 dose
    Intervention: Drug: Ibrutinib
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 13, 2016)
45
Original Estimated Enrollment  ICMJE
 (submitted: July 16, 2014)
39
Actual Study Completion Date  ICMJE September 15, 2017
Actual Primary Completion Date September 15, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02195869
Other Study ID Numbers  ICMJE PCYC-1129-CA
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pharmacyclics LLC.
Study Sponsor  ICMJE Pharmacyclics LLC.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Lori Styles, MD Pharmacyclics LLC.
PRS Account Pharmacyclics LLC.
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP