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

Overview

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.

Full Title of Study: “A Multicenter Open-Label Phase 1b/2 Study of Ibrutinib in Steroid Dependent or Refractory Chronic Graft Versus Host Disease”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: September 15, 2017

Interventions

  • Drug: Ibrutinib

Arms, Groups and Cohorts

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

Clinical Trial Outcome Measures

Primary Measures

  • 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).

Secondary Measures

  • 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

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Pharmacyclics LLC.
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Lori Styles, MD, Study Director, Pharmacyclics LLC.

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