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

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).

Population: Endpoint only includes Phase 1 data.

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.

Population: Efficacy analyses were performed using the All-treated Population (N = 42)

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.

Population: Phase 2 subjects includes all subjects who participated in Phase 1b.

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.

Population: All subjects who received at least 1 dose of ibrutinib at the recommended Phase 2 dose.

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

Population: Phase 2 subjects includes all subjects who participated in Phase 1b

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.

Population: Phase 2 subjects include all subjects who participated in phase 1b. Subjects evaluated for sustained response includes participants who had achieved an NIH-defined CR or PR.

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.

Population: Phase 2 subjects includes all subjects who participated in Phase 1b