Trial Outcomes & Findings for Safety and Efficacy of Ruxolitinib Versus Best Available Therapy in Patients With Corticosteroid-refractory Acute Graft vs. Host Disease After Allogeneic Stem Cell Transplantation (NCT NCT02913261)

Last Updated: 2023-02-08

Results Overview

Overall response rate at Day 28 after randomization was defined as the percentage participants in each arm demonstrating a complete response (CR) or partial response (PR), based on investigator assessment \& according to standard criteria, without requirement for additional systemic therapies for an earlier progression, mixed response or non-response. Scoring of response was relative to the organ stage at the time of randomization. CR was defined as a score of 0 for the aGvHD grading in all evaluable organs that indicates complete resolution of all signs \& symptoms of aGvHD in all evaluable organs without administration of additional systemic therapies for any earlier progression, mixed response or non-response of aGvHD. PR was defined as improvement of 1 stage in 1 or more organs involved with aGvHD signs or symptoms without progression in other organs or sites without administration of additional systemic therapies for an earlier progression, mixed response or non-response of aGvHD.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

310 participants

Primary outcome timeframe

Day 28

Results posted on

2023-02-08

Participant Flow

A total of 310 patients with SR-aGvHD were enrolled, out of which 309 patients were included in the analysis (as one patient did not sign the study informed consent prior to receiving BAT (protocol deviation) and was excluded from all analyses). Completed = Completed the treatment period Not completed = Discontinued from treatment period

The screening period ranged from Day -28 to Day -1. Screening activities and assessment of inclusion and exclusion criteria began once the patient was diagnosed with aGvHD. Any occurrence of SR-aGvHD was monitored closely.

Participant milestones

Participant milestones
Measure	Ruxolitinib (RUX) These patients were administered Ruxolitinib orally twice per day (b.i.d) at a dose of 10 mg bid, as two 5-mg tablets. Ruxolitinib was taken without regards to food.	Best Available Therapy (BAT) These patients were administered BAT per the Investigator's best judgement based on a specific list of BAT.
Overall Study STARTED	154	155
Overall Study Not Treated	2	5
Overall Study Crossover Treatment at End of Randomized Treatment	0	49
Overall Study Entered Long-term Follow-up	102	51
Overall Study Completed Screening & Randomized	154	155
Overall Study Completed Screening & Not Randomized	0	1
Overall Study COMPLETED	35	20
Overall Study NOT COMPLETED	119	135

Reasons for withdrawal

Reasons for withdrawal
Measure	Ruxolitinib (RUX) These patients were administered Ruxolitinib orally twice per day (b.i.d) at a dose of 10 mg bid, as two 5-mg tablets. Ruxolitinib was taken without regards to food.	Best Available Therapy (BAT) These patients were administered BAT per the Investigator's best judgement based on a specific list of BAT.
Overall Study Technical problems	0	1
Overall Study Lack of Efficacy	32	69
Overall Study Adverse Event	27	5
Overall Study Death	25	22
Overall Study Failure to meet protocol continuation criteria	13	10
Overall Study Disease relapse	8	13
Overall Study Physician Decision	8	9
Overall Study Subject/guardian decision	4	6
Overall Study Graft loss	2	0

Baseline Characteristics

the weight at baseline was missing for 7 patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ruxolitinib (RUX) n=154 Participants These patients were administered Ruxolitinib orally twice per day (b.i.d) at a dose of 10 mg bid, as two 5-mg tablets. Ruxolitinib was taken without regards to food.	Best Available Therapy (BAT) n=155 Participants These patients were administered BAT per the Investigator's best judgement based on a specific list of BAT.	Total n=309 Participants Total of all reporting groups
Age, Continuous	48.1 years STANDARD_DEVIATION 16.30 • n=154 Participants	50.9 years STANDARD_DEVIATION 14.97 • n=155 Participants	49.5 years STANDARD_DEVIATION 15.69 • n=309 Participants
Age, Customized Adolescents, 12 - <18 years	5 Participants n=154 Participants	4 Participants n=155 Participants	9 Participants n=309 Participants
Age, Customized 18 - 65 years	128 Participants n=154 Participants	126 Participants n=155 Participants	254 Participants n=309 Participants
Age, Customized >65 years	21 Participants n=154 Participants	25 Participants n=155 Participants	46 Participants n=309 Participants
Sex: Female, Male Female	62 Participants n=154 Participants	64 Participants n=155 Participants	126 Participants n=309 Participants
Sex: Female, Male Male	92 Participants n=154 Participants	91 Participants n=155 Participants	183 Participants n=309 Participants
Race/Ethnicity, Customized White	111 Participants n=154 Participants	102 Participants n=155 Participants	213 Participants n=309 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=154 Participants	1 Participants n=155 Participants	1 Participants n=309 Participants
Race/Ethnicity, Customized Asian	19 Participants n=154 Participants	29 Participants n=155 Participants	48 Participants n=309 Participants
Race/Ethnicity, Customized Other	8 Participants n=154 Participants	4 Participants n=155 Participants	12 Participants n=309 Participants
Race/Ethnicity, Customized Unknown	16 Participants n=154 Participants	19 Participants n=155 Participants	35 Participants n=309 Participants
Weight	67.5 kg STANDARD_DEVIATION 14.04 • n=150 Participants • the weight at baseline was missing for 7 patients	66.2 kg STANDARD_DEVIATION 14.78 • n=152 Participants • the weight at baseline was missing for 7 patients	66.9 kg STANDARD_DEVIATION 14.41 • n=302 Participants • the weight at baseline was missing for 7 patients

PRIMARY outcome

Timeframe: Day 28

Population: The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization.

Outcome measures

Outcome measures
Measure	Ruxolitinib (RUX) n=154 Participants These patients were administered Ruxolitinib orally twice per day (b.i.d) at a dose of 10 mg bid, as two 5-mg tablets. Ruxolitinib was taken without regards to food.	Best Available Therapy (BAT) n=155 Participants These patients were administered BAT per the Investigator's best judgement based on a specific list of BAT.	Cross-Over These were patients randomized to BAT who were eligible to cross over to Ruxolitinib between Day 28 and Week 24.
Overall Response Rate (ORR) at Day 28	62.3 Percentage of participants Interval 54.2 to 70.0	39.4 Percentage of participants Interval 31.6 to 47.5	—

SECONDARY outcome

Timeframe: Day 56

Population: The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization.

Percentage of all participants in each arm who achieved a complete response (CR) or partial response (PR) at Day 28 (primary endpoint) AND maintained a CR or PR at Day 56 based on investigator assessment and according to standard criteria. CR was defined as a score of 0 for the aGvHD grading in all evaluable organs that indicates complete resolution of all signs and symptoms of aGvHD in all evaluable organs without administration of additional systemic therapies for any earlier progression, mixed response or non-response of aGvHD. PR was defined as improvement of 1 stage in 1 or more organs involved with aGvHD signs or symptoms without progression in other organs or sites without administration of additional systemic therapies for an earlier progression, mixed response or non-response of aGvHD.

Outcome measures

Outcome measures
Measure	Ruxolitinib (RUX) n=154 Participants These patients were administered Ruxolitinib orally twice per day (b.i.d) at a dose of 10 mg bid, as two 5-mg tablets. Ruxolitinib was taken without regards to food.	Best Available Therapy (BAT) n=155 Participants These patients were administered BAT per the Investigator's best judgement based on a specific list of BAT.	Cross-Over These were patients randomized to BAT who were eligible to cross over to Ruxolitinib between Day 28 and Week 24.
Durable Overall Response Rate (DORR) (Key Secondary Endpoint) at Day 56	39.6 Percentage of participants Interval 31.8 to 47.8	21.9 Percentage of participants Interval 15.7 to 29.3	—

SECONDARY outcome

Timeframe: Day 14

Population: The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization.

ORR at Da4 14 is the percentage of participants who achieved overall response (CR+PR) at Day 14 based on investigator assessment and according to standard criteria. CR was defined as a score of 0 for the aGvHD grading in all evaluable organs that indicates complete resolution of all signs and symptoms of aGvHD in all evaluable organs without administration of additional systemic therapies for any earlier progression, mixed response or non-response of aGvHD. PR was defined as improvement of 1 stage in 1 or more organs involved with aGvHD signs or symptoms without progression in other organs or sites without administration of additional systemic therapies for an earlier progression, mixed response or non-response of aGvHD.

Outcome measures

Outcome measures
Measure	Ruxolitinib (RUX) n=154 Participants These patients were administered Ruxolitinib orally twice per day (b.i.d) at a dose of 10 mg bid, as two 5-mg tablets. Ruxolitinib was taken without regards to food.	Best Available Therapy (BAT) n=155 Participants These patients were administered BAT per the Investigator's best judgement based on a specific list of BAT.	Cross-Over These were patients randomized to BAT who were eligible to cross over to Ruxolitinib between Day 28 and Week 24.
Overall Response Rate (ORR) at Day 14	63.0 Percentage of participants Interval 54.8 to 70.6	47.1 Percentage of participants Interval 39.0 to 55.3	—

SECONDARY outcome

Timeframe: Up to 24 months

Population: The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization. These were patients to whom study treatment was assigned by randomization and whose overall response was complete response (CR) or partial response (PR).

Duration of response was defined for patients who had a CR or PR at Day 28. This was the interval between the date of first documented response of CR or PR (i.e., the start date of response), till the date of progression or addition of systemic therapies for aGvHD on or after Day 28. Death without prior observation of aGvHD progression and onset of chronic GvHD were considered. Duration of response was censored at the last response assessment prior to or at the analysis cut-off date, if no events/competing risk occurred before or at the cut-off date.

Outcome measures

Outcome measures
Measure	Ruxolitinib (RUX) n=98 Participants These patients were administered Ruxolitinib orally twice per day (b.i.d) at a dose of 10 mg bid, as two 5-mg tablets. Ruxolitinib was taken without regards to food.	Best Available Therapy (BAT) n=62 Participants These patients were administered BAT per the Investigator's best judgement based on a specific list of BAT.	Cross-Over These were patients randomized to BAT who were eligible to cross over to Ruxolitinib between Day 28 and Week 24.
Duration of Response (DOR)	167.0 Days Interval 22.0 to 677.0	106.0 Days Interval 10.0 to 526.0	—

SECONDARY outcome

Timeframe: up to Day 56

Population: The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization.

Weekly cumulative steroid dose for each participant up to Day 56 or discontinuation of randomized treatment. Participants should have undergone tapering of steroids if it had been required. Tapering the immunosuppression therapy was performed in 2 steps: Taper of corticosteroids: initiated not earlier than Day 7, and performed as per institutional guidelines. Only patients with assessments done at each time point are reported. This is the reason that the overall number per treatment is higher and the number of participants with responses vary over time.

Outcome measures

Outcome measures
Measure	Ruxolitinib (RUX) n=154 Participants These patients were administered Ruxolitinib orally twice per day (b.i.d) at a dose of 10 mg bid, as two 5-mg tablets. Ruxolitinib was taken without regards to food.	Best Available Therapy (BAT) n=155 Participants These patients were administered BAT per the Investigator's best judgement based on a specific list of BAT.	Cross-Over These were patients randomized to BAT who were eligible to cross over to Ruxolitinib between Day 28 and Week 24.
Cumulative Steroid Dosing Until Day 56 By Week 1	962.5 mg Interval 140.0 to 2337.5	923.6 mg Interval 140.0 to 6093.8	—
Cumulative Steroid Dosing Until Day 56 By Week 2	1740.0 mg Interval 280.0 to 3500.0	1725.0 mg Interval 280.0 to 7173.3	—
Cumulative Steroid Dosing Until Day 56 By Week 3	2375.0 mg Interval 350.0 to 5250.0	2340.0 mg Interval 370.0 to 8000.0	—
Cumulative Steroid Dosing Until Day 56 By Week 4	2866.9 mg Interval 420.0 to 7000.0	2816.3 mg Interval 420.0 to 9050.0	—
Cumulative Steroid Dosing Until Day 56 By Week 5	3268.1 mg Interval 455.0 to 8750.0	3290.6 mg Interval 420.0 to 9825.0	—
Cumulative Steroid Dosing Until Day 56 By Week 6	3606.3 mg Interval 490.0 to 10500.0	3543.8 mg Interval 420.0 to 10435.0	—
Cumulative Steroid Dosing Until Day 56 By Week 7	3850.0 mg Interval 495.0 to 11250.0	3706.3 mg Interval 420.0 to 10955.0	—
Cumulative Steroid Dosing Until Day 56 By Week 8	4000.0 mg Interval 857.5 to 9475.0	4006.3 mg Interval 420.0 to 11875.0	—

SECONDARY outcome

Timeframe: 1, 2, 6, 12, 18 & 24 months

Population: The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization.

OS was defined as the time from the date of randomization to date of death due to any cause. If a patient was not known to have died, then OS was censored at the latest date the patient was known to be alive (on or before the cut-off date). Results are based on Kaplan Meier (KM) estimates.

Outcome measures

Outcome measures
Measure	Ruxolitinib (RUX) n=154 Participants These patients were administered Ruxolitinib orally twice per day (b.i.d) at a dose of 10 mg bid, as two 5-mg tablets. Ruxolitinib was taken without regards to food.	Best Available Therapy (BAT) n=155 Participants These patients were administered BAT per the Investigator's best judgement based on a specific list of BAT.	Cross-Over These were patients randomized to BAT who were eligible to cross over to Ruxolitinib between Day 28 and Week 24.
Kaplan Meier Estimates of Probability of Overall Survival (OS) by Time Interval 1 Month	90.04 Percentage of participants Interval 84.02 to 93.87	85.48 Percentage of participants Interval 78.79 to 90.19	—
Kaplan Meier Estimates of Probability of Overall Survival (OS) by Time Interval 2 Months	77.95 Percentage of participants Interval 70.42 to 83.79	75.69 Percentage of participants Interval 67.92 to 81.83	—
Kaplan Meier Estimates of Probability of Overall Survival (OS) by Time Interval 6 Months	58.38 Percentage of participants Interval 50.03 to 65.82	49.42 Percentage of participants Interval 40.89 to 57.37	—
Kaplan Meier Estimates of Probability of Overall Survival (OS) by Time Interval 12 Months	49.27 Percentage of participants Interval 40.96 to 57.05	42.71 Percentage of participants Interval 34.39 to 50.75	—
Kaplan Meier Estimates of Probability of Overall Survival (OS) by Time Interval 18 Months	42.94 Percentage of participants Interval 34.82 to 50.79	37.97 Percentage of participants Interval 29.86 to 46.03	—
Kaplan Meier Estimates of Probability of Overall Survival (OS) by Time Interval 24 Months	38.65 Percentage of participants Interval 30.5 to 46.72	35.55 Percentage of participants Interval 27.57 to 43.59	—

SECONDARY outcome

Timeframe: 1, 2, 6, 12, 18 & 24 months

Population: The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization.

Event-free survival was defined as the time from the date of randomization to the date of hematologic disease relapse/progression, graft failure, or death due to any cause. If a patient was not known to have any event, then EFS was censored at the latest date the patient was known to be alive (on or before the cut-off date). Results are based on Kaplan Meier (KM) estimates.

Outcome measures

Outcome measures
Measure	Ruxolitinib (RUX) n=154 Participants These patients were administered Ruxolitinib orally twice per day (b.i.d) at a dose of 10 mg bid, as two 5-mg tablets. Ruxolitinib was taken without regards to food.	Best Available Therapy (BAT) n=155 Participants These patients were administered BAT per the Investigator's best judgement based on a specific list of BAT.	Cross-Over These were patients randomized to BAT who were eligible to cross over to Ruxolitinib between Day 28 and Week 24.
Kaplan Meier Estimates of Probability of Event-free Survival (EFS) by Time Interval 1 Month	89.38 Percentage of participants Interval 83.24 to 93.35	82.83 Percentage of participants Interval 75.81 to 87.97	—
Kaplan Meier Estimates of Probability of Event-free Survival (EFS) by Time Interval 2 Months	74.60 Percentage of participants Interval 66.82 to 80.82	71.72 Percentage of participants Interval 63.71 to 78.26	—
Kaplan Meier Estimates of Probability of Event-free Survival (EFS) by Time Interval 6 Months	53.68 Percentage of participants Interval 45.34 to 61.3	44.14 Percentage of participants Interval 35.82 to 52.13	—
Kaplan Meier Estimates of Probability of Event-free Survival (EFS) by Time Interval 12 Months	44.53 Percentage of participants Interval 36.36 to 52.36	39.98 Percentage of participants Interval 30.9 to 46.96	—
Kaplan Meier Estimates of Probability of Event-free Survival (EFS) by Time Interval 18 Months	40.29 Percentage of participants Interval 32.3 to 48.12	35.09 Percentage of participants Interval 27.23 to 43.04	—
Kaplan Meier Estimates of Probability of Event-free Survival (EFS) by Time Interval 24 Months	34.98 Percentage of participants Interval 27.01 to 43.04	32.38 Percentage of participants Interval 24.61 to 40.37	—

SECONDARY outcome

Timeframe: 1, 2, 6, 12, 18, & 24 Months

Population: The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization.

FFS was defined as the time from the date of randomization to date of hematologic disease relapse/progression, non-relapse mortality, or addition of new systemic aGvHD treatment. Probability of FFS with 95% CIs are presented for each treatment group, accounting for onset of chronic GvHD as the competing risk.

Outcome measures

Outcome measures
Measure	Ruxolitinib (RUX) n=154 Participants These patients were administered Ruxolitinib orally twice per day (b.i.d) at a dose of 10 mg bid, as two 5-mg tablets. Ruxolitinib was taken without regards to food.	Best Available Therapy (BAT) n=155 Participants These patients were administered BAT per the Investigator's best judgement based on a specific list of BAT.	Cross-Over These were patients randomized to BAT who were eligible to cross over to Ruxolitinib between Day 28 and Week 24.
Cumulative Incidence Rate of Failure-Free Survival (FFS) 1 Month	17.92 Cumulative probability of FFS Interval 12.26 to 24.46	49.13 Cumulative probability of FFS Interval 40.94 to 56.8	—
Cumulative Incidence Rate of Failure-Free Survival (FFS) 2 Months	35.39 Cumulative probability of FFS Interval 27.79 to 43.07	61.32 Cumulative probability of FFS Interval 53.0 to 68.61	—
Cumulative Incidence Rate of Failure-Free Survival (FFS) 6 Months	53.67 Cumulative probability of FFS Interval 45.28 to 61.34	80.17 Cumulative probability of FFS Interval 72.52 to 85.89	—
Cumulative Incidence Rate of Failure-Free Survival (FFS) 12 Months	58.64 Cumulative probability of FFS Interval 50.18 to 66.16	80.91 Cumulative probability of FFS Interval 73.32 to 86.54	—
Cumulative Incidence Rate of Failure-Free Survival (FFS) 18 Months	59.35 Cumulative probability of FFS Interval 50.88 to 66.84	80.91 Cumulative probability of FFS Interval 73.32 to 86.54	—
Cumulative Incidence Rate of Failure-Free Survival (FFS) 24 Months	61.48 Cumulative probability of FFS Interval 53.01 to 68.88	81.66 Cumulative probability of FFS Interval 74.12 to 87.19	—

SECONDARY outcome

Timeframe: 1, 2, 6, 12, 18 & 24 months

Population: The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization.

NRM was defined as the time from date of randomization to date of death not preceded by hematologic disease relapse/progression. Hematologic disease relapse/progression was considered a competing risk for NRM with the date of hematologic disease relapse/progression being the earlier of documented hematologic disease relapse/progression or institution of therapy to treat potential hematologic disease relapse/progression. If a patient was not known to have died or to have relapsed/progressed, then NRM was censored at the latest date the patient was known to be alive (on or before the cut-off date). Data is provided based on cumulative probability of hematologic disease relapse/progression.

Outcome measures

Outcome measures
Measure	Ruxolitinib (RUX) n=154 Participants These patients were administered Ruxolitinib orally twice per day (b.i.d) at a dose of 10 mg bid, as two 5-mg tablets. Ruxolitinib was taken without regards to food.	Best Available Therapy (BAT) n=155 Participants These patients were administered BAT per the Investigator's best judgement based on a specific list of BAT.	Cross-Over These were patients randomized to BAT who were eligible to cross over to Ruxolitinib between Day 28 and Week 24.
Cumulative Probability of Non Relapse Mortality (NRM) 1 Month	9.96 Cumulative probability of NRM Interval 5.83 to 15.39	14.52 Cumulative probability of NRM Interval 9.45 to 20.64	—
Cumulative Probability of Non Relapse Mortality (NRM) 2 Months	20.71 Cumulative probability of NRM Interval 14.61 to 27.54	23.54 Cumulative probability of NRM Interval 17.04 to 30.65	—
Cumulative Probability of Non Relapse Mortality (NRM) 6 Months	37.59 Cumulative probability of NRM Interval 29.81 to 45.33	42.42 Cumulative probability of NRM Interval 34.18 to 50.41	—
Cumulative Probability of Non Relapse Mortality (NRM) 12 Months	43.91 Cumulative probability of NRM Interval 35.75 to 51.77	46.11 Cumulative probability of NRM Interval 37.68 to 54.12	—
Cumulative Probability of Non Relapse Mortality (NRM) 18 Months	46.03 Cumulative probability of NRM Interval 37.77 to 53.89	49.21 Cumulative probability of NRM Interval 40.63 to 57.22	—
Cumulative Probability of Non Relapse Mortality (NRM) 24 Months	49.53 Cumulative probability of NRM Interval 40.91 to 57.55	49.99 Cumulative probability of NRM Interval 41.38 to 57.99	—

SECONDARY outcome

Timeframe: 1, 2, 6, 12 , 18 & 24 months

Population: The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization. Calculated for patients with underlying hematologic malignant disease.

MR was defined as the time from date of randomization to hematologic malignancy relapse/progression. Deaths not preceded by hematologic malignancy relapse/progression were considered competing risks. If a patient was not known to have event or competing risks, then MR was censored at the latest date the patient was known to be alive (on or before the cut-off date). Calculated for patients with underlying hematologic malignant disease.

Outcome measures

Outcome measures
Measure	Ruxolitinib (RUX) n=147 Participants These patients were administered Ruxolitinib orally twice per day (b.i.d) at a dose of 10 mg bid, as two 5-mg tablets. Ruxolitinib was taken without regards to food.	Best Available Therapy (BAT) n=147 Participants These patients were administered BAT per the Investigator's best judgement based on a specific list of BAT.	Cross-Over These were patients randomized to BAT who were eligible to cross over to Ruxolitinib between Day 28 and Week 24.
Cumulative Probability of Malignancy Relapse/Progression (MR) 1 Month	0.69 Cumulative probability of MR Interval 0.06 to 3.51	2.80 Cumulative probability of MR Interval 0.92 to 6.54	—
Cumulative Probability of Malignancy Relapse/Progression (MR) 2 Months	4.21 Cumulative probability of MR Interval 1.73 to 8.46	4.29 Cumulative probability of MR Interval 1.75 to 8.6	—
Cumulative Probability of Malignancy Relapse/Progression (MR) 6 Months	8.46 Cumulative probability of MR Interval 4.6 to 13.79	13.49 Cumulative probability of MR Interval 8.32 to 19.91	—
Cumulative Probability of Malignancy Relapse/Progression (MR) 12 Months	10.68 Cumulative probability of MR Interval 6.24 to 16.47	15.06 Cumulative probability of MR Interval 9.56 to 21.71	—
Cumulative Probability of Malignancy Relapse/Progression (MR) 18 Months	12.91 Cumulative probability of MR Interval 7.96 to 19.09	16.72 Cumulative probability of MR Interval 10.89 to 23.64	—
Cumulative Probability of Malignancy Relapse/Progression (MR) 24 Months	14.75 Cumulative probability of MR Interval 9.32 to 21.37	18.81 Cumulative probability of MR Interval 12.46 to 26.17	—

SECONDARY outcome

Timeframe: 1, 2, 6, 12, 18 & 24 months

Population: The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization. Calculated for patients with underlying hematologic malignant disease.

Incidence of cGvHD was the time from date of randomization to onset of cGvHD is the diagnosis of any cGvHD including mild, moderate, severe. Deaths without prior onset of cGvHD and hematologic disease relapse/progression were competing risks. If a patient was not known to have event or competing risks, then the incidence of cGvHD was censored at the latest date the patient was known to be alive (on or before the cut-off date).

Outcome measures

Outcome measures
Measure	Ruxolitinib (RUX) n=154 Participants These patients were administered Ruxolitinib orally twice per day (b.i.d) at a dose of 10 mg bid, as two 5-mg tablets. Ruxolitinib was taken without regards to food.	Best Available Therapy (BAT) n=155 Participants These patients were administered BAT per the Investigator's best judgement based on a specific list of BAT.	Cross-Over These were patients randomized to BAT who were eligible to cross over to Ruxolitinib between Day 28 and Week 24.
Cumulative Probability of Chronic Graft Versus Host Disease (cGvHD) 1 Month	0 Cumulative probability of cGvHD N/A: 95% CI could not be achieved as there was no incidence of cGvHD	1.33 Cumulative probability of cGvHD Interval 0.26 to 4.34	—
Cumulative Probability of Chronic Graft Versus Host Disease (cGvHD) 2 Months	1.34 Cumulative probability of cGvHD Interval 0.26 to 4.39	2.03 Cumulative probability of cGvHD Interval 0.55 to 5.41	—
Cumulative Probability of Chronic Graft Versus Host Disease (cGvHD) 6 Months	15.60 Cumulative probability of cGvHD Interval 10.26 to 21.96	12.19 Cumulative probability of cGvHD Interval 7.4 to 18.25	—
Cumulative Probability of Chronic Graft Versus Host Disease (cGvHD) 12 Months	29.66 Cumulative probability of cGvHD Interval 22.41 to 37.25	20.24 Cumulative probability of cGvHD Interval 13.98 to 27.34	—
Cumulative Probability of Chronic Graft Versus Host Disease (cGvHD) 18 Months	32.48 Cumulative probability of cGvHD Interval 24.96 to 40.2	23.36 Cumulative probability of cGvHD Interval 16.62 to 30.76	—
Cumulative Probability of Chronic Graft Versus Host Disease (cGvHD) 24 Months	36.00 Cumulative probability of cGvHD Interval 28.2 to 43.84	24.95 Cumulative probability of cGvHD Interval 18.0 to 32.5	—

SECONDARY outcome

Timeframe: Day 28

Population: PK-Efficacy Set: All patients randomized to ruxolitinib treatment arm, who received at least one dose of ruxolitinib, who have post-baseline efficacy data (at least one efficacy parameter) and for whom popPK predictions are available (at least one popPK predicted AUC0-12h).

Exposure-efficacy relationship of ruxolitinib in terms of concentration-effect and dose-effect. ORR was defined as the percentage of participants with a best overall response defined as complete response (CR) or partial response (PR) as assessed by local investigators. CR was defined as a score of 0 for the Acute Graft vs. Host Disease (aGvHD) grading in all evaluable organs that indicates complete resolution of all signs and symptoms of aGvHD in all evaluable organs without administration of additional systemic therapies for any earlier progression, mixed response or non-response of aGvHD. PR was defined as improvement of 1 stage in 1 or more organs involved with aGvHD signs or symptoms without progression in other organs or sites without administration of additional systemic therapies for an earlier progression, mixed response or non-response of aGvHD.

Outcome measures

Outcome measures
Measure	Ruxolitinib (RUX) n=118 Participants These patients were administered Ruxolitinib orally twice per day (b.i.d) at a dose of 10 mg bid, as two 5-mg tablets. Ruxolitinib was taken without regards to food.	Best Available Therapy (BAT) These patients were administered BAT per the Investigator's best judgement based on a specific list of BAT.	Cross-Over These were patients randomized to BAT who were eligible to cross over to Ruxolitinib between Day 28 and Week 24.
Exposure-efficacy Relationship of Ruxolitinib in Corticosteroid Refractory aGvHD: PK-Overall Response Rate	82.2 Percentage of participants	—	—

SECONDARY outcome

Timeframe: Day 56

Population: PK-Efficacy Set: PK-Efficacy Set: All patients randomized to ruxolitinib treatment arm, who received at least one dose of ruxolitinib, who have post-baseline efficacy data (at least one efficacy parameter) and for whom popPK predictions are available (at least one popPK predicted AUC0-12h).

Exposure-efficacy relationship of ruxolitinib in terms of concentration-effect and dose-effect. DORR is the percentage of all participants in each arm who achieved a complete response (CR) or partial response (PR) at Day 28 (primary endpoint) AND maintained a CR or PR at Day 56. CR was defined as a score of 0 for the aGvHD grading in all evaluable organs that indicates complete resolution of all signs and symptoms of aGvHD in all evaluable organs without administration of additional systemic therapies for any earlier progression, mixed response or non-response of aGvHD. PR was defined as improvement of 1 stage in 1 or more organs involved with aGvHD signs or symptoms without progression in other organs or sites without administration of additional systemic therapies for an earlier progression, mixed response or non-response of aGvHD.

Outcome measures

Outcome measures
Measure	Ruxolitinib (RUX) n=67 Participants These patients were administered Ruxolitinib orally twice per day (b.i.d) at a dose of 10 mg bid, as two 5-mg tablets. Ruxolitinib was taken without regards to food.	Best Available Therapy (BAT) These patients were administered BAT per the Investigator's best judgement based on a specific list of BAT.	Cross-Over These were patients randomized to BAT who were eligible to cross over to Ruxolitinib between Day 28 and Week 24.
Exposure-efficacy Relationship of Ruxolitinib in Corticosteroid Refractory aGvHD: PK- Durable Overall Response Rate (DORR)	91.0 Percentage of participants	—	—

SECONDARY outcome

Timeframe: up to 24 months

Exposure-efficacy relationship of ruxolitinib in terms of concentration-effect and dose-effect. This represents the percentage of Ruxolitinib-exposed participants dead at 24 months. Overall survival (OS) was defined as the time from the date of randomization to date of death due to any cause. If a patient was not known to have died, then OS was censored at the latest date the patient was known to be alive (on or before the cut-off date).the date of death due to any cause.

Outcome measures

Outcome measures
Measure	Ruxolitinib (RUX) n=150 Participants These patients were administered Ruxolitinib orally twice per day (b.i.d) at a dose of 10 mg bid, as two 5-mg tablets. Ruxolitinib was taken without regards to food.	Best Available Therapy (BAT) These patients were administered BAT per the Investigator's best judgement based on a specific list of BAT.	Cross-Over These were patients randomized to BAT who were eligible to cross over to Ruxolitinib between Day 28 and Week 24.
Exposure-efficacy Relationship of Ruxolitinib in Corticosteroid Refractory aGvHD: PK-Overall Survival	53.3 Percentage of participants	—	—

SECONDARY outcome

Timeframe: up to Day 28

Population: The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization. These were participants whose overall response was complete response (CR) or partial response (PR).

Percentage of participants who achieved overall response (OR) (CR+PR) at any time point up to and including Day 28 and before the start of additional systemic therapy for aGvHD. CR was defined as a score of 0 for the Acute Graft vs. Host Disease (aGvHD) grading in all evaluable organs that indicates complete resolution of all signs and symptoms of aGvHD in all evaluable organs without administration of additional systemic therapies for any earlier progression, mixed response or non-response of aGvHD. PR was defined as improvement of 1 stage in 1 or more organs involved with aGvHD signs or symptoms without progression in other organs or sites without administration of additional systemic therapies for an earlier progression, mixed response or non-response of aGvHD.

Outcome measures

Outcome measures
Measure	Ruxolitinib (RUX) n=154 Participants These patients were administered Ruxolitinib orally twice per day (b.i.d) at a dose of 10 mg bid, as two 5-mg tablets. Ruxolitinib was taken without regards to food.	Best Available Therapy (BAT) n=155 Participants These patients were administered BAT per the Investigator's best judgement based on a specific list of BAT.	Cross-Over These were patients randomized to BAT who were eligible to cross over to Ruxolitinib between Day 28 and Week 24.
Best Overall Response Rate (BOR)	81.8 Percentage of participants Interval 74.8 to 87.6	60.6 Percentage of participants Interval 52.5 to 68.4	—

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization.

The Functional assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) is a 50-item self-report questionnaire that measures the effect of a therapy on domains including physical, functional, social/family and emotional well-being, together with additional concerns relevant for bone marrow transplantation patients. Patients indicated their response on a scale of 0 to 4 on each statement, with 0 indicating worst score and 4 the best score. All individual scores were combined to calculate the total score. Total score was reported with score range: 0-148 which was calculated as the sum of all unweighted subscale scores. The higher the total score the better the result. Descriptive statistics and change from baseline were calculated in total score at each scheduled assessment time point.

Outcome measures

Outcome measures
Measure	Ruxolitinib (RUX) n=154 Participants These patients were administered Ruxolitinib orally twice per day (b.i.d) at a dose of 10 mg bid, as two 5-mg tablets. Ruxolitinib was taken without regards to food.	Best Available Therapy (BAT) n=155 Participants These patients were administered BAT per the Investigator's best judgement based on a specific list of BAT.	Cross-Over These were patients randomized to BAT who were eligible to cross over to Ruxolitinib between Day 28 and Week 24.
Patient Reported Outcomes (PROs): Change From Baseline in Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) Total Score Baseline	89.00 scores on a scale Interval 41.0 to 138.0	81.00 scores on a scale Interval 29.0 to 129.0	—
Patient Reported Outcomes (PROs): Change From Baseline in Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) Total Score Week (W) 24	108.50 scores on a scale Interval 67.0 to 139.0	86.00 scores on a scale Interval 21.0 to 124.0	—
Patient Reported Outcomes (PROs): Change From Baseline in Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) Total Score Change from Baseline to W24	9.00 scores on a scale Interval -40.0 to 44.0	4.50 scores on a scale Interval -29.0 to 41.0	—

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization.

The EQ-5D descriptive classification consists of five dimensions of health: mobility, self-care, usual activities, anxiety/depression and pain/discomfort. Patients are requested to select the statement which best describes their condition on that day for each dimension. For overall health that day, the EuroQoL-5D-5L scale is numbered from 0 to 100, with 100 being the best health you can imagine and 0 being the worst health you can imagine. Descriptive statistics (mean, standard deviation, median, Q1, Q3, minimum, and maximum) were calculated based on the scored scales at each scheduled assessment time point. In order to measure Quality-of-Life (QoL) among aGvHD patients, and potential changes over time, change from baseline in EuroQol-5D-5L scores at the time of each assessment were also calculated. Missing items data in a scale will be handled based on each instrument manual. No imputation will be applied if the total or subscale scores are missing at a visit.

Outcome measures

Outcome measures
Measure	Ruxolitinib (RUX) n=154 Participants These patients were administered Ruxolitinib orally twice per day (b.i.d) at a dose of 10 mg bid, as two 5-mg tablets. Ruxolitinib was taken without regards to food.	Best Available Therapy (BAT) n=155 Participants These patients were administered BAT per the Investigator's best judgement based on a specific list of BAT.	Cross-Over These were patients randomized to BAT who were eligible to cross over to Ruxolitinib between Day 28 and Week 24.
Patient Reported Outcomes (PROs): Change From Baseline in EuroQol-5D-5L UK Score Baseline	0.60 scores on a scale Interval -0.6 to 1.0	0.54 scores on a scale Interval -0.6 to 1.0	—
Patient Reported Outcomes (PROs): Change From Baseline in EuroQol-5D-5L UK Score W24	0.78 scores on a scale Interval 0.4 to 1.0	0.68 scores on a scale Interval -0.1 to 1.0	—
Patient Reported Outcomes (PROs): Change From Baseline in EuroQol-5D-5L UK Score Change from Baseline to W24	0.12 scores on a scale Interval -0.3 to 1.1	0.12 scores on a scale Interval -0.2 to 0.3	—

SECONDARY outcome

Timeframe: pre-dose, 0.5, 1, 1.5, 2, 4, 6, 9 hrs post-dose

Population: The Pharmacokinetic Analysis Set (PAS) included all patients who provided at least one evaluable PK concentration. For a concentration to be evaluable, patients were required to: Take a dose of ruxolitinib prior to sampling, Did not vomit within 2 hours after the last dose of ruxolitinib prior to sampling (for pre dose samples) or did not vomit within 2 hours after ruxolitinib dosing (for post dose samples).

AUClast: The AUC from time zero to the last measurable concentration sampling time (tlast) (mass x time x volume-1) AUCinf: The AUC from time zero to infinity (mass x time x volume-1) AUCtau: The AUC calculated to the end of a dosing interval (tau) at steady-state (amount x time x volume-1). Plasma samples for PK was taken at Day 1 (start of treatment), at Day 7 (week 1) to characterize the PK after first dose, and at steady state by non-compartmental analysis. The plasma samples from all patients was assayed for ruxolitinib concentrations using validated liquid chromatography-tandem mass spectrometry method (LC-MS/MS).

Outcome measures

Outcome measures
Measure	Ruxolitinib (RUX) n=26 Participants These patients were administered Ruxolitinib orally twice per day (b.i.d) at a dose of 10 mg bid, as two 5-mg tablets. Ruxolitinib was taken without regards to food.	Best Available Therapy (BAT) These patients were administered BAT per the Investigator's best judgement based on a specific list of BAT.	Cross-Over These were patients randomized to BAT who were eligible to cross over to Ruxolitinib between Day 28 and Week 24.
Pharmacokinetic (PK) Parameter: Area Under the Curve (AUC) (AUCinf, AUClast, AUCtau) of Ruxolitinib Week 1 Day 1 AUCinf	529.6 ng*hr/mL Geometric Coefficient of Variation 55.2	—	—
Pharmacokinetic (PK) Parameter: Area Under the Curve (AUC) (AUCinf, AUClast, AUCtau) of Ruxolitinib Week 1 Day 1 AUClast	522.9 ng*hr/mL Geometric Coefficient of Variation 89.6	—	—
Pharmacokinetic (PK) Parameter: Area Under the Curve (AUC) (AUCinf, AUClast, AUCtau) of Ruxolitinib Week 1 Day 1 AUCtau	578.9 ng*hr/mL Geometric Coefficient of Variation 97.5	—	—
Pharmacokinetic (PK) Parameter: Area Under the Curve (AUC) (AUCinf, AUClast, AUCtau) of Ruxolitinib Week 1 Day 7 AUCinf	440.9 ng*hr/mL Geometric Coefficient of Variation 91.5	—	—
Pharmacokinetic (PK) Parameter: Area Under the Curve (AUC) (AUCinf, AUClast, AUCtau) of Ruxolitinib Week 1 Day 7 AUClast	597.3 ng*hr/mL Geometric Coefficient of Variation 73.2	—	—
Pharmacokinetic (PK) Parameter: Area Under the Curve (AUC) (AUCinf, AUClast, AUCtau) of Ruxolitinib Week 1 Day 7 AUCtau	651.9 ng*hr/mL Geometric Coefficient of Variation 86.4	—	—

SECONDARY outcome

Timeframe: pre-dose, 0.5, 1, 1.5, 2, 4, 6, 9 hrs post-dose

Cmax is the maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration (mass X volume-1). Plasma samples for PK was taken at Day 1 (start of treatment), at Day 7 (week 1) to characterize the PK after first dose, and at steady state by non-compartmental analysis. The plasma samples from all patients was assayed for ruxolitinib concentrations using validated liquid chromatography-tandem mass spectrometry method (LC-MS/MS).

Outcome measures

Outcome measures
Measure	Ruxolitinib (RUX) n=26 Participants These patients were administered Ruxolitinib orally twice per day (b.i.d) at a dose of 10 mg bid, as two 5-mg tablets. Ruxolitinib was taken without regards to food.	Best Available Therapy (BAT) These patients were administered BAT per the Investigator's best judgement based on a specific list of BAT.	Cross-Over These were patients randomized to BAT who were eligible to cross over to Ruxolitinib between Day 28 and Week 24.
Pharmacokinetic (PK) Parameter: Plasma Concentration at Peak (Cmax) of Ruxolitinib Week 1 Day 1	118 ng/mL Geometric Coefficient of Variation 70.4	—	—
Pharmacokinetic (PK) Parameter: Plasma Concentration at Peak (Cmax) of Ruxolitinib Week 1 Day 7	129.3 ng/mL Geometric Coefficient of Variation 76.0	—	—

SECONDARY outcome

Timeframe: pre-dose, 0.5, 1, 1.5, 2, 4, 6, 9 hrs post-dose

CL/F is the total body clearance of ruxolitinib from the plasma after a single dose and at steady state. Plasma samples for PK was taken at Day 1 (start of treatment), at Day 7 (week 1) to characterize the PK after first dose, and at steady state by non-compartmental analysis. The plasma samples from all patients was assayed for Ruxolitinib concentrations using validated liquid chromatography-tandem mass spectrometry method (LC-MS/MS).

Outcome measures

Outcome measures
Measure	Ruxolitinib (RUX) n=11 Participants These patients were administered Ruxolitinib orally twice per day (b.i.d) at a dose of 10 mg bid, as two 5-mg tablets. Ruxolitinib was taken without regards to food.	Best Available Therapy (BAT) These patients were administered BAT per the Investigator's best judgement based on a specific list of BAT.	Cross-Over These were patients randomized to BAT who were eligible to cross over to Ruxolitinib between Day 28 and Week 24.
Pharmacokinetic (PK) Parameter: CL/F of Ruxolitinib Week 1 Day 1 CL/F	18.88 L/hr Geometric Coefficient of Variation 55.2	—	—
Pharmacokinetic (PK) Parameter: CL/F of Ruxolitinib Week 1 Day 7 CL/F	23.31 L/hr Geometric Coefficient of Variation 89.4	—	—

SECONDARY outcome

Timeframe: pre-dose, 0.5, 1, 1.5, 2, 4, 6, 9 hrs post-dose

VzF is the apparent volume of distribution during terminal phase after a single dose and at steady state. Plasma samples for PK was taken at Day 1 (start of treatment), at Day 7 (week 1) to characterize the PK after first dose, and at steady state by non-compartmental analysis. The plasma samples from all patients will be assayed for ruxolitinib concentrations using validated liquid chromatography-tandem mass spectrometry method (LC-MS/MS).

Outcome measures

Outcome measures
Measure	Ruxolitinib (RUX) n=11 Participants These patients were administered Ruxolitinib orally twice per day (b.i.d) at a dose of 10 mg bid, as two 5-mg tablets. Ruxolitinib was taken without regards to food.	Best Available Therapy (BAT) These patients were administered BAT per the Investigator's best judgement based on a specific list of BAT.	Cross-Over These were patients randomized to BAT who were eligible to cross over to Ruxolitinib between Day 28 and Week 24.
Pharmacokinetic (PK) Parameter: VzF of Ruxolitinib Week 1 Day 1	52.57 Liters (L) Geometric Coefficient of Variation 46.4	—	—
Pharmacokinetic (PK) Parameter: VzF of Ruxolitinib Week 1 Day 7	66.76 Liters (L) Geometric Coefficient of Variation 71.6	—	—

SECONDARY outcome

Timeframe: pre-dose, 0.5, 1, 1.5, 2, 4, 6, 9 hrs post-dose

Lambda\_z is the smallest (slowest) disposition (hybrid) rate constant (hr-1) may also be used for terminal elimination rate constant (hr-1). Plasma samples for PK was taken at Day 1 (start of treatment), at Day 7 (week 1) to characterize the PK after first dose, and at steady state by non-compartmental analysis. The plasma samples from all patients will be assayed for ruxolitinib concentrations using validated liquid chromatography-tandem mass spectrometry method (LC-MS/MS).

Outcome measures

Outcome measures
Measure	Ruxolitinib (RUX) n=11 Participants These patients were administered Ruxolitinib orally twice per day (b.i.d) at a dose of 10 mg bid, as two 5-mg tablets. Ruxolitinib was taken without regards to food.	Best Available Therapy (BAT) These patients were administered BAT per the Investigator's best judgement based on a specific list of BAT.	Cross-Over These were patients randomized to BAT who were eligible to cross over to Ruxolitinib between Day 28 and Week 24.
Pharmacokinetic (PK) Parameter: Lambda_z of Ruxolitinib Week 1 Day 1	0.3592 1/hr Geometric Coefficient of Variation 34.2	—	—
Pharmacokinetic (PK) Parameter: Lambda_z of Ruxolitinib Week 1 Day 7	0.3492 1/hr Geometric Coefficient of Variation 31.0	—	—

SECONDARY outcome

Timeframe: pre-dose, 0.5, 1, 1.5, 2, 4, 6, 9 hrs post-dose

T1/2 is the elimination half-life associated with the terminal slope of a semi logarithmic concentration-time curve (hr). Plasma samples for PK was taken at Day 1 (start of treatment), at Day 7 (week 1) to characterize the PK after first dose, and at steady state by non-compartmental analysis. The plasma samples from all patients will be assayed for ruxolitinib concentrations using validated liquid chromatography-tandem mass spectrometry method (LC-MS/MS).

Outcome measures

Outcome measures
Measure	Ruxolitinib (RUX) n=11 Participants These patients were administered Ruxolitinib orally twice per day (b.i.d) at a dose of 10 mg bid, as two 5-mg tablets. Ruxolitinib was taken without regards to food.	Best Available Therapy (BAT) These patients were administered BAT per the Investigator's best judgement based on a specific list of BAT.	Cross-Over These were patients randomized to BAT who were eligible to cross over to Ruxolitinib between Day 28 and Week 24.
Pharmacokinetic (PK) Parameter: T1/2 of Ruxolitinib Week 1 Day 1	1.93 hour (hr) Geometric Coefficient of Variation 34.2	—	—
Pharmacokinetic (PK) Parameter: T1/2 of Ruxolitinib Week 1 Day 7	1.985 hour (hr) Geometric Coefficient of Variation 31.0	—	—

SECONDARY outcome

Timeframe: pre-dose, 0.5, 1, 1.5, 2, 4, 6, 9 hrs post-dose

Tmax is the time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose and repeated dose administration (hr). Plasma samples for PK was taken at Day 1 (start of treatment), at Day 7 (week 1) to characterize the PK after first dose, and at steady state by non-compartmental analysis. The plasma samples from all patients will be assayed for ruxolitinib concentrations using validated liquid chromatography-tandem mass spectrometry method (LC-MS/MS).

Outcome measures

Outcome measures
Measure	Ruxolitinib (RUX) n=26 Participants These patients were administered Ruxolitinib orally twice per day (b.i.d) at a dose of 10 mg bid, as two 5-mg tablets. Ruxolitinib was taken without regards to food.	Best Available Therapy (BAT) These patients were administered BAT per the Investigator's best judgement based on a specific list of BAT.	Cross-Over These were patients randomized to BAT who were eligible to cross over to Ruxolitinib between Day 28 and Week 24.
Pharmacokinetic (PK) Parameter: Tmax of Ruxolitinib Week 1 Day 1	1.767 hour (hr) Interval 0.5167 to 8.917	—	—
Pharmacokinetic (PK) Parameter: Tmax of Ruxolitinib Week 1 Day 7	1.542 hour (hr) Interval 0.5 to 4.083	—	—

SECONDARY outcome

Timeframe: pre-dose, 0.5, 1, 1.5, 2, 4, 6, 9 hrs post-dose

Racc is the accumulation ratio (AUC at steady state/AUC Day 1). Plasma samples for PK was taken at Day 1 (start of treatment), at Day 7 (week 1) to characterize the PK after first dose, and at steady state by non-compartmental analysis. The plasma samples from all patients was be assayed for ruxolitinib concentrations using validated liquid chromatography-tandem mass spectrometry method (LC-MS/MS).

Outcome measures

Outcome measures
Measure	Ruxolitinib (RUX) n=26 Participants These patients were administered Ruxolitinib orally twice per day (b.i.d) at a dose of 10 mg bid, as two 5-mg tablets. Ruxolitinib was taken without regards to food.	Best Available Therapy (BAT) These patients were administered BAT per the Investigator's best judgement based on a specific list of BAT.	Cross-Over These were patients randomized to BAT who were eligible to cross over to Ruxolitinib between Day 28 and Week 24.
Pharmacokinetic (PK) Parameter: Racc of Ruxolitinib	1.145 ratio Geometric Coefficient of Variation 27.2	—	—

SECONDARY outcome

Timeframe: pre-dose

Minimum concentration (Ctrough) of ruxolitinib and at steady state in corticosteroid refractory acute GVHD patients. Plasma samples for PK was taken at Day 1 (start of treatment), at Day 7 (week 1) to characterize the PK after first dose, and at steady state by non-compartmental analysis. The plasma samples from all patients will be assayed for ruxolitinib concentrations using validated liquid chromatography-tandem mass spectrometry method (LC-MS/MS)

Outcome measures

Outcome measures
Measure	Ruxolitinib (RUX) n=152 Participants These patients were administered Ruxolitinib orally twice per day (b.i.d) at a dose of 10 mg bid, as two 5-mg tablets. Ruxolitinib was taken without regards to food.	Best Available Therapy (BAT) These patients were administered BAT per the Investigator's best judgement based on a specific list of BAT.	Cross-Over These were patients randomized to BAT who were eligible to cross over to Ruxolitinib between Day 28 and Week 24.
Pharmacokinetic (PK) Parameter: Ctrough of Ruxolitinib	17.22 ng/ml Geometric Coefficient of Variation 187.1	—	—

POST_HOC outcome

Timeframe: approx. 708 days (AEs), up to approx. 48 months (deaths)

Population: Clinical Database Population: all randomized patients

On treatment deaths were collected from the start of treatment up to 30 days after study drug discontinuation, for a maximum duration of 708 days (treatment duration ranged from 6.0 to 678.0) for the RUX arm and 218 days (treatment duration ranged from 1.0 to 188.0 days) for the BAT arm. Deaths post treatment survival follow up were collected after the on- treatment period, up to approx. 48 months. Patients who didn't die during the on-treatment period and had not stopped study participation at the time of data cut-off (end of study) were censored.

Outcome measures

Outcome measures
Measure	Ruxolitinib (RUX) n=152 Participants These patients were administered Ruxolitinib orally twice per day (b.i.d) at a dose of 10 mg bid, as two 5-mg tablets. Ruxolitinib was taken without regards to food.	Best Available Therapy (BAT) n=150 Participants These patients were administered BAT per the Investigator's best judgement based on a specific list of BAT.	Cross-Over n=49 Participants These were patients randomized to BAT who were eligible to cross over to Ruxolitinib between Day 28 and Week 24.
All Collected Deaths Total Deaths	89 Participants	89 Participants	29 Participants
All Collected Deaths Deaths on-treatment	43 Participants	36 Participants	19 Participants

Adverse Events

Ruxolitinib (Rux)

Serious events: 101 serious events

Other events: 144 other events

Deaths: 89 deaths

Best Available Therapy (BAT)

Serious events: 80 serious events

Other events: 136 other events

Deaths: 89 deaths

Cross-Over

Serious events: 38 serious events

Other events: 43 other events

Deaths: 29 deaths

Serious adverse events

Other adverse events

Additional Information

Study Directr

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety
Publication restrictions are in place

Restriction type: OTHER