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Completed

NCT Number: NCT02195869

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

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.

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Key information

Conditions

Graft Versus Host Disease Bronchial Diseases Bronchiolitis Bronchiolitis Obliterans Bronchiolitis Obliterans Syndrome Bronchitis Graft vs Host Disease Immune System Diseases Lung Diseases Lung Diseases, Obstructive Organizing Pneumonia Respiratory Tract Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

City of Hope Medical Center, Duarte, California, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Ibrutinib

Drug

Other names: PCI32765

Primary outcomes

  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 outcomes

  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

Sponsors and collaborators

Lead sponsor

Pharmacyclics LLC.

Industry

Registry information

Official study title

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

Important dates

Study start
2014
Primary completion
2017
Study completion
2017
First posted
Jul 21, 2014
Registry last updated
Jul 11, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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