Corticosteroid Refractory Acute Graft vs Host Disease
Conditions
Keywords
GvHD (Graft versus Host Disease), INC424, ruxolitinib, best available therapy (BAT), corticosteroid-refractory acute graft vs. host disease, allogeneic stem cell transplantation, steroid refractory acute graft vs. host disease, Janus Kinase (JAK) inhibitor
Brief summary
Assess the efficacy and safety of ruxolitinib compared to Best Available Therapy (BAT) in patients with corticosteroid-refractory acute graft vs. host disease (aGvHD) after allogeneic stem cell transplantation.
Detailed description
This randomized, phase III, open-label study investigated the efficacy and safety of ruxolitinib vs. BAT added to the patient's immunosuppressive regimen in adults and adolescents (≥ 12 years old) with grade II-IV Steroid-refractory Acute Graft vs. Host Disease (SR-aGvHD). During the screening period, patients were monitored for a diagnosis of SR-aGvHD, which was defined as patients who had high-dose systemic corticosteroids (methylprednisolone 2 mg/kg/day \[or equivalent prednisone dose 2.5 mg/kg/day\]), given alone or combined with CNI, who either: 1. Progressed based on organ assessment after at least 3 days compared to organ stage at the time of initiation of high-dose systemic corticosteroid +/- CNI for the treatment of Grade II-IV aGvHD, OR 2. Failed to achieve at a minimum a partial response based on organ assessment after 7 days compared to organ stage at the time of initiation of high-dose systemic corticosteroid +/- CNI for the treatment of Grade II-IV aGvHD, OR 3. Failed corticosteroid taper defined as fulfilling either one of the following criteria: * Requirement for an increase in the corticosteroid dose to methylprednisolone ≥ 2 mg/kg/day (or equivalent prednisone dose ≥ 2.5 mg/kg/day) OR * Failure to taper the methylprednisolone dose to \<0.5 mg/kg/day (or equivalent prednisone dose \<0.6 mg/kg/day) for a minimum 7 days. Patients meeting eligibility criteria were randomized 1:1 to receive either ruxolitinib or BAT stratifying on aGvHD grade at the time of randomization (Grade II vs III vs IV). Study treatment began on Day 1 (no later than 72 hours after randomization) followed by regular visits for assessments of efficacy and safety. Study treatment was administered until the patient met any of the criteria for discontinuation of study treatment or, in responders (i.e. patients achieving PR or CR) until the dosing schedule for ruxolitinib or BAT was completed. All responders were to be tapered off during the treatment period by, first tapering from corticosteroids, followed by CNI and ruxolitinib. A slow tapering extending beyond 24 weeks was permitted for ruxolitinib at Investigator's discretion rather than an abrupt cessation, as the latter could result in an aGvHD flare. During the Treatment Period, patients randomized to BAT could have crossed over to ruxolitinib between Day 28 and Week 24 if they: * Failed to meet the primary endpoint response definition (CR or PR) at Day 28 OR * Lost the response thereafter and met criteria for progression, mixed response, or no response, necessitating new additional systemic immunosuppressive treatment for aGvHD. AND \- Did not have signs/symptoms of chronic Graft vs. Host Disease (cGvHD) (overlap syndrome, progressive, or de novo cGvHD) Patients who crossed over to ruxolitinib were followed until completion of treatment with ruxolitinib and received the same treatment and tapering schedule as patients randomized to ruxolitinib treatment. The End of Treatment (EOT) visit occurred when the patient completed the study treatment period or earlier if the patient met any of the criteria for discontinuation of study treatment. Patient's treatment period was up to 6 months (Week 24). However, ruxolitinib taper could be delayed up to 2 years from randomization due to an aGvHD flare or other safety concerns.
Interventions
Ruxolitinib was provided as 5 mg tablets for oral use.
BAT was based on the investigator's best judgment, taking into account the manufacturer's instructions, labeling, patient's medical condition, and institutional guidelines for any dose adjustment. The BAT in this study was identified by the investigator prior to patient randomization among the following treatments currently used in this setting: anti-thymocyte globulin (ATG), extracorporeal photopheresis (ECP), mesenchymal stromal cells (MSC), low-dose methotrexate (MTX), mycophenolate mofetil (MMF), mTOR inhibitors (everolimus or sirolimus), etanercept, or infliximab. No other types or combinations of BAT were permitted.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have undergone Allogeneic Stem Cell Transplanttaion (alloSCT) from any donor source (matched unrelated donor, sibling, haplo-identical) using bone marrow, peripheral blood stem cells, or cord blood. Recipients of non- myeloablative, myeloablative, and reduced intensity conditioning are eligible * Clinically diagnosed Grades II to IV acute GvHD as per standard criteria occurring after alloSCT requiring systemic immune suppressive therapy. Biopsy of involved organs with aGvHD is encouraged but not required for study screening. * Confirmed diagnosis of steroid refractory aGvHD defined as patients administered high-dose systemic corticosteroids (methylprednisolone 2 mg/kg/day \[or equivalent prednisone dose 2.5 mg/kg/day\]), given alone or combined with calcineurin inhibitors (CNI) and either: * Progressing based on organ assessment after at least 3 days compared to organ stage at the time of initiation of high-dose systemic corticosteroid +/- CNI for the treatment of Grade II-IV aGvHD, OR * Failure to achieve at a minimum partial response based on organ assessment after 7 days compared to organ stage at the time of initiation of high-dose systemic corticosteroid +/- CNI for the treatment of Grade II-IV aGvHD,OR * Patients who fail corticosteroid taper defined as fulfilling either one of the following criteria: * Requirement for an increase in the corticosteroid dose to methylprednisolone ≥2 mg/kg/day (or equivalent prednisone dose ≥2.5 mg/kg/day) , OR * Failure to taper the methylprednisolone dose to \<0.5 mg/kg/day (or equivalent prednisone dose \<0.6 mg/kg/day) for a minimum 7 days.
Exclusion criteria
* Has received more than one systemic treatment for steroid refractory aGvHD. * Presence of an active uncontrolled infection including significant bacterial, fungal, viral or parasitic infection requiring treatment. Infections are considered controlled if appropriate therapy has been instituted and, at the time of screening, no signs of progression are present. Progression of infection is defined as hemodynamic instability attributable to sepsis, new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection. * Evidence of uncontrolled viral infection including Cytomegalovirus (CMV), Epstein-Barr Virus (EBV), Human Herpes Virus-6 (HHV-6), Hepatitis Virus (HBV), or Hepatitis C Virus (HCV) based on assessment by the treating physician. * Presence of relapsed primary malignancy, or who have been treated for relapse after the alloHSCT was performed, or who may require rapid immune suppression withdrawal as pre-emergent treatment of early malignancy relapse.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) at Day 28 | Day 28 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) at Day 14 | Day 14 | 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. |
| Duration of Response (DOR) | Up to 24 months | 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. |
| Cumulative Steroid Dosing Until Day 56 | up to Day 56 | 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. |
| Kaplan Meier Estimates of Probability of Overall Survival (OS) by Time Interval | 1, 2, 6, 12, 18 & 24 months | 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. |
| Kaplan Meier Estimates of Probability of Event-free Survival (EFS) by Time Interval | 1, 2, 6, 12, 18 & 24 months | 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. |
| Cumulative Incidence Rate of Failure-Free Survival (FFS) | 1, 2, 6, 12, 18, & 24 Months | 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. |
| Cumulative Probability of Non Relapse Mortality (NRM) | 1, 2, 6, 12, 18 & 24 months | 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. |
| Cumulative Probability of Malignancy Relapse/Progression (MR) | 1, 2, 6, 12 , 18 & 24 months | 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. |
| Cumulative Probability of Chronic Graft Versus Host Disease (cGvHD) | 1, 2, 6, 12, 18 & 24 months | 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). |
| Exposure-efficacy Relationship of Ruxolitinib in Corticosteroid Refractory aGvHD: PK-Overall Response Rate | Day 28 | 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. |
| Exposure-efficacy Relationship of Ruxolitinib in Corticosteroid Refractory aGvHD: PK- Durable Overall Response Rate (DORR) | Day 56 | 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. |
| Exposure-efficacy Relationship of Ruxolitinib in Corticosteroid Refractory aGvHD: PK-Overall Survival | 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. |
| Durable Overall Response Rate (DORR) (Key Secondary Endpoint) at Day 56 | Day 56 | 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. |
| Patient Reported Outcomes (PROs): Change From Baseline in Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) Total Score | Baseline, Week 24 | 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. |
| Patient Reported Outcomes (PROs): Change From Baseline in EuroQol-5D-5L UK Score | Baseline, Week 24 | 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. |
| Pharmacokinetic (PK) Parameter: Area Under the Curve (AUC) (AUCinf, AUClast, AUCtau) of Ruxolitinib | pre-dose, 0.5, 1, 1.5, 2, 4, 6, 9 hrs post-dose | 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). |
| Pharmacokinetic (PK) Parameter: Plasma Concentration at Peak (Cmax) of Ruxolitinib | 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). |
| Pharmacokinetic (PK) Parameter: CL/F of Ruxolitinib | 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). |
| Pharmacokinetic (PK) Parameter: VzF of Ruxolitinib | 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). |
| Pharmacokinetic (PK) Parameter: Lambda_z of Ruxolitinib | 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). |
| Pharmacokinetic (PK) Parameter: T1/2 of Ruxolitinib | 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). |
| Pharmacokinetic (PK) Parameter: Tmax of Ruxolitinib | 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). |
| Pharmacokinetic (PK) Parameter: Racc of Ruxolitinib | 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). |
| Pharmacokinetic (PK) Parameter: Ctrough of Ruxolitinib | 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) |
| Best Overall Response Rate (BOR) | up to Day 28 | 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. |
Countries
Australia, Austria, Bulgaria, Canada, Czechia, Denmark, France, Germany, Greece, Hong Kong, Israel, Italy, Japan, Netherlands, Norway, Russia, Saudi Arabia, South Korea, Spain, Taiwan, Turkey (Türkiye), United Kingdom
Participant flow
Recruitment details
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
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 154 |
| Best Available Therapy (BAT) These patients were administered BAT per the Investigator's best judgement based on a specific list of BAT. | 155 |
| Total | 309 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 27 | 5 |
| Overall Study | Death | 25 | 22 |
| Overall Study | Disease relapse | 8 | 13 |
| Overall Study | Failure to meet protocol continuation criteria | 13 | 10 |
| Overall Study | Graft loss | 2 | 0 |
| Overall Study | Lack of Efficacy | 32 | 69 |
| Overall Study | Physician Decision | 8 | 9 |
| Overall Study | Subject/guardian decision | 4 | 6 |
| Overall Study | Technical problems | 0 | 1 |
Baseline characteristics
| Characteristic | Ruxolitinib (RUX) | Total | Best Available Therapy (BAT) |
|---|---|---|---|
| Age, Continuous | 48.1 years STANDARD_DEVIATION 16.3 | 49.5 years STANDARD_DEVIATION 15.69 | 50.9 years STANDARD_DEVIATION 14.97 |
| Age, Customized 18 - 65 years | 128 Participants | 254 Participants | 126 Participants |
| Age, Customized >65 years | 21 Participants | 46 Participants | 25 Participants |
| Age, Customized Adolescents, 12 - <18 years | 5 Participants | 9 Participants | 4 Participants |
| Race/Ethnicity, Customized Asian | 19 Participants | 48 Participants | 29 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 8 Participants | 12 Participants | 4 Participants |
| Race/Ethnicity, Customized Unknown | 16 Participants | 35 Participants | 19 Participants |
| Race/Ethnicity, Customized White | 111 Participants | 213 Participants | 102 Participants |
| Sex: Female, Male Female | 62 Participants | 126 Participants | 64 Participants |
| Sex: Female, Male Male | 92 Participants | 183 Participants | 91 Participants |
| Weight | 67.5 kg STANDARD_DEVIATION 14.04 | 66.9 kg STANDARD_DEVIATION 14.41 | 66.2 kg STANDARD_DEVIATION 14.78 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 89 / 152 | 89 / 150 | 29 / 49 |
| other Total, other adverse events | 144 / 152 | 136 / 150 | 43 / 49 |
| serious Total, serious adverse events | 101 / 152 | 80 / 150 | 38 / 49 |
Outcome results
Primary
Overall Response Rate (ORR) at Day 28
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.
Time frame: Day 28
Population: The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ruxolitinib (RUX) | Overall Response Rate (ORR) at Day 28 | 62.3 Percentage of participants |
| Best Available Therapy (BAT) | Overall Response Rate (ORR) at Day 28 | 39.4 Percentage of participants |
p-value: <0.000195% CI: [1.65, 4.22]Stratified Cochran-Mantel-Haenszel
Secondary
Best Overall Response Rate (BOR)
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.
Time frame: 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).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ruxolitinib (RUX) | Best Overall Response Rate (BOR) | 81.8 Percentage of participants |
| Best Available Therapy (BAT) | Best Overall Response Rate (BOR) | 60.6 Percentage of participants |
p-value: <0.000195% CI: [1.8, 5.25]Stratified Cochran-Mantel-Haenszel
Secondary
Cumulative Incidence Rate of Failure-Free Survival (FFS)
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.
Time frame: 1, 2, 6, 12, 18, & 24 Months
Population: The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ruxolitinib (RUX) | Cumulative Incidence Rate of Failure-Free Survival (FFS) | 1 Month | 17.92 Cumulative probability of FFS |
| Ruxolitinib (RUX) | Cumulative Incidence Rate of Failure-Free Survival (FFS) | 2 Months | 35.39 Cumulative probability of FFS |
| Ruxolitinib (RUX) | Cumulative Incidence Rate of Failure-Free Survival (FFS) | 6 Months | 53.67 Cumulative probability of FFS |
| Ruxolitinib (RUX) | Cumulative Incidence Rate of Failure-Free Survival (FFS) | 12 Months | 58.64 Cumulative probability of FFS |
| Ruxolitinib (RUX) | Cumulative Incidence Rate of Failure-Free Survival (FFS) | 18 Months | 59.35 Cumulative probability of FFS |
| Ruxolitinib (RUX) | Cumulative Incidence Rate of Failure-Free Survival (FFS) | 24 Months | 61.48 Cumulative probability of FFS |
| Best Available Therapy (BAT) | Cumulative Incidence Rate of Failure-Free Survival (FFS) | 18 Months | 80.91 Cumulative probability of FFS |
| Best Available Therapy (BAT) | Cumulative Incidence Rate of Failure-Free Survival (FFS) | 1 Month | 49.13 Cumulative probability of FFS |
| Best Available Therapy (BAT) | Cumulative Incidence Rate of Failure-Free Survival (FFS) | 12 Months | 80.91 Cumulative probability of FFS |
| Best Available Therapy (BAT) | Cumulative Incidence Rate of Failure-Free Survival (FFS) | 2 Months | 61.32 Cumulative probability of FFS |
| Best Available Therapy (BAT) | Cumulative Incidence Rate of Failure-Free Survival (FFS) | 24 Months | 81.66 Cumulative probability of FFS |
| Best Available Therapy (BAT) | Cumulative Incidence Rate of Failure-Free Survival (FFS) | 6 Months | 80.17 Cumulative probability of FFS |
Secondary
Cumulative Probability of Chronic Graft Versus Host Disease (cGvHD)
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).
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ruxolitinib (RUX) | Cumulative Probability of Chronic Graft Versus Host Disease (cGvHD) | 1 Month | 0 Cumulative probability of cGvHD |
| Ruxolitinib (RUX) | Cumulative Probability of Chronic Graft Versus Host Disease (cGvHD) | 6 Months | 15.60 Cumulative probability of cGvHD |
| Ruxolitinib (RUX) | Cumulative Probability of Chronic Graft Versus Host Disease (cGvHD) | 12 Months | 29.66 Cumulative probability of cGvHD |
| Ruxolitinib (RUX) | Cumulative Probability of Chronic Graft Versus Host Disease (cGvHD) | 18 Months | 32.48 Cumulative probability of cGvHD |
| Ruxolitinib (RUX) | Cumulative Probability of Chronic Graft Versus Host Disease (cGvHD) | 24 Months | 36.00 Cumulative probability of cGvHD |
| Ruxolitinib (RUX) | Cumulative Probability of Chronic Graft Versus Host Disease (cGvHD) | 2 Months | 1.34 Cumulative probability of cGvHD |
| Best Available Therapy (BAT) | Cumulative Probability of Chronic Graft Versus Host Disease (cGvHD) | 24 Months | 24.95 Cumulative probability of cGvHD |
| Best Available Therapy (BAT) | Cumulative Probability of Chronic Graft Versus Host Disease (cGvHD) | 1 Month | 1.33 Cumulative probability of cGvHD |
| Best Available Therapy (BAT) | Cumulative Probability of Chronic Graft Versus Host Disease (cGvHD) | 2 Months | 2.03 Cumulative probability of cGvHD |
| Best Available Therapy (BAT) | Cumulative Probability of Chronic Graft Versus Host Disease (cGvHD) | 18 Months | 23.36 Cumulative probability of cGvHD |
| Best Available Therapy (BAT) | Cumulative Probability of Chronic Graft Versus Host Disease (cGvHD) | 6 Months | 12.19 Cumulative probability of cGvHD |
| Best Available Therapy (BAT) | Cumulative Probability of Chronic Graft Versus Host Disease (cGvHD) | 12 Months | 20.24 Cumulative probability of cGvHD |
Secondary
Cumulative Probability of Malignancy Relapse/Progression (MR)
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ruxolitinib (RUX) | Cumulative Probability of Malignancy Relapse/Progression (MR) | 18 Months | 12.91 Cumulative probability of MR |
| Ruxolitinib (RUX) | Cumulative Probability of Malignancy Relapse/Progression (MR) | 1 Month | 0.69 Cumulative probability of MR |
| Ruxolitinib (RUX) | Cumulative Probability of Malignancy Relapse/Progression (MR) | 12 Months | 10.68 Cumulative probability of MR |
| Ruxolitinib (RUX) | Cumulative Probability of Malignancy Relapse/Progression (MR) | 2 Months | 4.21 Cumulative probability of MR |
| Ruxolitinib (RUX) | Cumulative Probability of Malignancy Relapse/Progression (MR) | 24 Months | 14.75 Cumulative probability of MR |
| Ruxolitinib (RUX) | Cumulative Probability of Malignancy Relapse/Progression (MR) | 6 Months | 8.46 Cumulative probability of MR |
| Best Available Therapy (BAT) | Cumulative Probability of Malignancy Relapse/Progression (MR) | 24 Months | 18.81 Cumulative probability of MR |
| Best Available Therapy (BAT) | Cumulative Probability of Malignancy Relapse/Progression (MR) | 12 Months | 15.06 Cumulative probability of MR |
| Best Available Therapy (BAT) | Cumulative Probability of Malignancy Relapse/Progression (MR) | 18 Months | 16.72 Cumulative probability of MR |
| Best Available Therapy (BAT) | Cumulative Probability of Malignancy Relapse/Progression (MR) | 6 Months | 13.49 Cumulative probability of MR |
| Best Available Therapy (BAT) | Cumulative Probability of Malignancy Relapse/Progression (MR) | 1 Month | 2.80 Cumulative probability of MR |
| Best Available Therapy (BAT) | Cumulative Probability of Malignancy Relapse/Progression (MR) | 2 Months | 4.29 Cumulative probability of MR |
Secondary
Cumulative Probability of Non Relapse Mortality (NRM)
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.
Time frame: 1, 2, 6, 12, 18 & 24 months
Population: The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ruxolitinib (RUX) | Cumulative Probability of Non Relapse Mortality (NRM) | 1 Month | 9.96 Cumulative probability of NRM |
| Ruxolitinib (RUX) | Cumulative Probability of Non Relapse Mortality (NRM) | 2 Months | 20.71 Cumulative probability of NRM |
| Ruxolitinib (RUX) | Cumulative Probability of Non Relapse Mortality (NRM) | 6 Months | 37.59 Cumulative probability of NRM |
| Ruxolitinib (RUX) | Cumulative Probability of Non Relapse Mortality (NRM) | 12 Months | 43.91 Cumulative probability of NRM |
| Ruxolitinib (RUX) | Cumulative Probability of Non Relapse Mortality (NRM) | 18 Months | 46.03 Cumulative probability of NRM |
| Ruxolitinib (RUX) | Cumulative Probability of Non Relapse Mortality (NRM) | 24 Months | 49.53 Cumulative probability of NRM |
| Best Available Therapy (BAT) | Cumulative Probability of Non Relapse Mortality (NRM) | 18 Months | 49.21 Cumulative probability of NRM |
| Best Available Therapy (BAT) | Cumulative Probability of Non Relapse Mortality (NRM) | 1 Month | 14.52 Cumulative probability of NRM |
| Best Available Therapy (BAT) | Cumulative Probability of Non Relapse Mortality (NRM) | 12 Months | 46.11 Cumulative probability of NRM |
| Best Available Therapy (BAT) | Cumulative Probability of Non Relapse Mortality (NRM) | 2 Months | 23.54 Cumulative probability of NRM |
| Best Available Therapy (BAT) | Cumulative Probability of Non Relapse Mortality (NRM) | 24 Months | 49.99 Cumulative probability of NRM |
| Best Available Therapy (BAT) | Cumulative Probability of Non Relapse Mortality (NRM) | 6 Months | 42.42 Cumulative probability of NRM |
Secondary
Cumulative Steroid Dosing Until Day 56
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.
Time frame: up to Day 56
Population: The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Ruxolitinib (RUX) | Cumulative Steroid Dosing Until Day 56 | By Week 1 | 962.5 mg |
| Ruxolitinib (RUX) | Cumulative Steroid Dosing Until Day 56 | By Week 2 | 1740.0 mg |
| Ruxolitinib (RUX) | Cumulative Steroid Dosing Until Day 56 | By Week 3 | 2375.0 mg |
| Ruxolitinib (RUX) | Cumulative Steroid Dosing Until Day 56 | By Week 4 | 2866.9 mg |
| Ruxolitinib (RUX) | Cumulative Steroid Dosing Until Day 56 | By Week 5 | 3268.1 mg |
| Ruxolitinib (RUX) | Cumulative Steroid Dosing Until Day 56 | By Week 6 | 3606.3 mg |
| Ruxolitinib (RUX) | Cumulative Steroid Dosing Until Day 56 | By Week 7 | 3850.0 mg |
| Ruxolitinib (RUX) | Cumulative Steroid Dosing Until Day 56 | By Week 8 | 4000.0 mg |
| Best Available Therapy (BAT) | Cumulative Steroid Dosing Until Day 56 | By Week 8 | 4006.3 mg |
| Best Available Therapy (BAT) | Cumulative Steroid Dosing Until Day 56 | By Week 1 | 923.6 mg |
| Best Available Therapy (BAT) | Cumulative Steroid Dosing Until Day 56 | By Week 5 | 3290.6 mg |
| Best Available Therapy (BAT) | Cumulative Steroid Dosing Until Day 56 | By Week 2 | 1725.0 mg |
| Best Available Therapy (BAT) | Cumulative Steroid Dosing Until Day 56 | By Week 7 | 3706.3 mg |
| Best Available Therapy (BAT) | Cumulative Steroid Dosing Until Day 56 | By Week 3 | 2340.0 mg |
| Best Available Therapy (BAT) | Cumulative Steroid Dosing Until Day 56 | By Week 6 | 3543.8 mg |
| Best Available Therapy (BAT) | Cumulative Steroid Dosing Until Day 56 | By Week 4 | 2816.3 mg |
Secondary
Durable Overall Response Rate (DORR) (Key Secondary Endpoint) at Day 56
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.
Time frame: Day 56
Population: The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ruxolitinib (RUX) | Durable Overall Response Rate (DORR) (Key Secondary Endpoint) at Day 56 | 39.6 Percentage of participants |
| Best Available Therapy (BAT) | Durable Overall Response Rate (DORR) (Key Secondary Endpoint) at Day 56 | 21.9 Percentage of participants |
p-value: 0.000595% CI: [1.43, 3.94]Stratified Cochran-Mantel-Haenszel
Secondary
Duration of Response (DOR)
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.
Time frame: 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).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ruxolitinib (RUX) | Duration of Response (DOR) | 167.0 Days |
| Best Available Therapy (BAT) | Duration of Response (DOR) | 106.0 Days |
Secondary
Exposure-efficacy Relationship of Ruxolitinib in Corticosteroid Refractory aGvHD: PK- Durable Overall Response Rate (DORR)
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.
Time frame: 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).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ruxolitinib (RUX) | Exposure-efficacy Relationship of Ruxolitinib in Corticosteroid Refractory aGvHD: PK- Durable Overall Response Rate (DORR) | 91.0 Percentage of participants |
Secondary
Exposure-efficacy Relationship of Ruxolitinib in Corticosteroid Refractory aGvHD: PK-Overall Response Rate
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.
Time frame: 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).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ruxolitinib (RUX) | Exposure-efficacy Relationship of Ruxolitinib in Corticosteroid Refractory aGvHD: PK-Overall Response Rate | 82.2 Percentage of participants |
Secondary
Exposure-efficacy Relationship of Ruxolitinib in Corticosteroid Refractory aGvHD: PK-Overall Survival
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.
Time frame: up to 24 months
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).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ruxolitinib (RUX) | Exposure-efficacy Relationship of Ruxolitinib in Corticosteroid Refractory aGvHD: PK-Overall Survival | 53.3 Percentage of participants |
Secondary
Kaplan Meier Estimates of Probability of Event-free Survival (EFS) by Time Interval
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.
Time frame: 1, 2, 6, 12, 18 & 24 months
Population: The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ruxolitinib (RUX) | Kaplan Meier Estimates of Probability of Event-free Survival (EFS) by Time Interval | 1 Month | 89.38 Percentage of participants |
| Ruxolitinib (RUX) | Kaplan Meier Estimates of Probability of Event-free Survival (EFS) by Time Interval | 2 Months | 74.60 Percentage of participants |
| Ruxolitinib (RUX) | Kaplan Meier Estimates of Probability of Event-free Survival (EFS) by Time Interval | 6 Months | 53.68 Percentage of participants |
| Ruxolitinib (RUX) | Kaplan Meier Estimates of Probability of Event-free Survival (EFS) by Time Interval | 12 Months | 44.53 Percentage of participants |
| Ruxolitinib (RUX) | Kaplan Meier Estimates of Probability of Event-free Survival (EFS) by Time Interval | 18 Months | 40.29 Percentage of participants |
| Ruxolitinib (RUX) | Kaplan Meier Estimates of Probability of Event-free Survival (EFS) by Time Interval | 24 Months | 34.98 Percentage of participants |
| Best Available Therapy (BAT) | Kaplan Meier Estimates of Probability of Event-free Survival (EFS) by Time Interval | 18 Months | 35.09 Percentage of participants |
| Best Available Therapy (BAT) | Kaplan Meier Estimates of Probability of Event-free Survival (EFS) by Time Interval | 1 Month | 82.83 Percentage of participants |
| Best Available Therapy (BAT) | Kaplan Meier Estimates of Probability of Event-free Survival (EFS) by Time Interval | 12 Months | 39.98 Percentage of participants |
| Best Available Therapy (BAT) | Kaplan Meier Estimates of Probability of Event-free Survival (EFS) by Time Interval | 2 Months | 71.72 Percentage of participants |
| Best Available Therapy (BAT) | Kaplan Meier Estimates of Probability of Event-free Survival (EFS) by Time Interval | 24 Months | 32.38 Percentage of participants |
| Best Available Therapy (BAT) | Kaplan Meier Estimates of Probability of Event-free Survival (EFS) by Time Interval | 6 Months | 44.14 Percentage of participants |
Secondary
Kaplan Meier Estimates of Probability of Overall Survival (OS) by Time Interval
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.
Time frame: 1, 2, 6, 12, 18 & 24 months
Population: The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ruxolitinib (RUX) | Kaplan Meier Estimates of Probability of Overall Survival (OS) by Time Interval | 1 Month | 90.04 Percentage of participants |
| Ruxolitinib (RUX) | Kaplan Meier Estimates of Probability of Overall Survival (OS) by Time Interval | 2 Months | 77.95 Percentage of participants |
| Ruxolitinib (RUX) | Kaplan Meier Estimates of Probability of Overall Survival (OS) by Time Interval | 6 Months | 58.38 Percentage of participants |
| Ruxolitinib (RUX) | Kaplan Meier Estimates of Probability of Overall Survival (OS) by Time Interval | 12 Months | 49.27 Percentage of participants |
| Ruxolitinib (RUX) | Kaplan Meier Estimates of Probability of Overall Survival (OS) by Time Interval | 18 Months | 42.94 Percentage of participants |
| Ruxolitinib (RUX) | Kaplan Meier Estimates of Probability of Overall Survival (OS) by Time Interval | 24 Months | 38.65 Percentage of participants |
| Best Available Therapy (BAT) | Kaplan Meier Estimates of Probability of Overall Survival (OS) by Time Interval | 18 Months | 37.97 Percentage of participants |
| Best Available Therapy (BAT) | Kaplan Meier Estimates of Probability of Overall Survival (OS) by Time Interval | 1 Month | 85.48 Percentage of participants |
| Best Available Therapy (BAT) | Kaplan Meier Estimates of Probability of Overall Survival (OS) by Time Interval | 12 Months | 42.71 Percentage of participants |
| Best Available Therapy (BAT) | Kaplan Meier Estimates of Probability of Overall Survival (OS) by Time Interval | 2 Months | 75.69 Percentage of participants |
| Best Available Therapy (BAT) | Kaplan Meier Estimates of Probability of Overall Survival (OS) by Time Interval | 24 Months | 35.55 Percentage of participants |
| Best Available Therapy (BAT) | Kaplan Meier Estimates of Probability of Overall Survival (OS) by Time Interval | 6 Months | 49.42 Percentage of participants |
Secondary
Overall Response Rate (ORR) at Day 14
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.
Time frame: Day 14
Population: The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ruxolitinib (RUX) | Overall Response Rate (ORR) at Day 14 | 63.0 Percentage of participants |
| Best Available Therapy (BAT) | Overall Response Rate (ORR) at Day 14 | 47.1 Percentage of participants |
p-value: 0.002995% CI: [1.24, 3.17]Stratified Cochran-Mantel-Haenszel
Secondary
Patient Reported Outcomes (PROs): Change From Baseline in EuroQol-5D-5L UK Score
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.
Time frame: Baseline, Week 24
Population: The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Ruxolitinib (RUX) | Patient Reported Outcomes (PROs): Change From Baseline in EuroQol-5D-5L UK Score | Baseline | 0.60 scores on a scale |
| Ruxolitinib (RUX) | Patient Reported Outcomes (PROs): Change From Baseline in EuroQol-5D-5L UK Score | W24 | 0.78 scores on a scale |
| Ruxolitinib (RUX) | Patient Reported Outcomes (PROs): Change From Baseline in EuroQol-5D-5L UK Score | Change from Baseline to W24 | 0.12 scores on a scale |
| Best Available Therapy (BAT) | Patient Reported Outcomes (PROs): Change From Baseline in EuroQol-5D-5L UK Score | Baseline | 0.54 scores on a scale |
| Best Available Therapy (BAT) | Patient Reported Outcomes (PROs): Change From Baseline in EuroQol-5D-5L UK Score | W24 | 0.68 scores on a scale |
| Best Available Therapy (BAT) | Patient Reported Outcomes (PROs): Change From Baseline in EuroQol-5D-5L UK Score | Change from Baseline to W24 | 0.12 scores on a scale |
Secondary
Patient Reported Outcomes (PROs): Change From Baseline in Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) Total Score
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.
Time frame: Baseline, Week 24
Population: The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Ruxolitinib (RUX) | 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 |
| Ruxolitinib (RUX) | 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 |
| Ruxolitinib (RUX) | 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 |
| Best Available Therapy (BAT) | Patient Reported Outcomes (PROs): Change From Baseline in Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) Total Score | Baseline | 81.00 scores on a scale |
| Best Available Therapy (BAT) | Patient Reported Outcomes (PROs): Change From Baseline in Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) Total Score | Week (W) 24 | 86.00 scores on a scale |
| Best Available Therapy (BAT) | 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 | 4.50 scores on a scale |
Secondary
Pharmacokinetic (PK) Parameter: Area Under the Curve (AUC) (AUCinf, AUClast, AUCtau) of Ruxolitinib
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).
Time frame: 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).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Ruxolitinib (RUX) | 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 |
| Ruxolitinib (RUX) | 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 |
| Ruxolitinib (RUX) | 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 |
| Ruxolitinib (RUX) | 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 |
| Ruxolitinib (RUX) | 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 |
| Ruxolitinib (RUX) | 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
Pharmacokinetic (PK) Parameter: CL/F of Ruxolitinib
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).
Time frame: 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).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Ruxolitinib (RUX) | Pharmacokinetic (PK) Parameter: CL/F of Ruxolitinib | Week 1 Day 1 CL/F | 18.88 L/hr | Geometric Coefficient of Variation 55.2 |
| Ruxolitinib (RUX) | Pharmacokinetic (PK) Parameter: CL/F of Ruxolitinib | Week 1 Day 7 CL/F | 23.31 L/hr | Geometric Coefficient of Variation 89.4 |
Secondary
Pharmacokinetic (PK) Parameter: Ctrough of Ruxolitinib
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)
Time frame: pre-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).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ruxolitinib (RUX) | Pharmacokinetic (PK) Parameter: Ctrough of Ruxolitinib | 17.22 ng/ml | Geometric Coefficient of Variation 187.1 |
Secondary
Pharmacokinetic (PK) Parameter: Lambda_z of Ruxolitinib
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).
Time frame: 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).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Ruxolitinib (RUX) | Pharmacokinetic (PK) Parameter: Lambda_z of Ruxolitinib | Week 1 Day 1 | 0.3592 1/hr | Geometric Coefficient of Variation 34.2 |
| Ruxolitinib (RUX) | Pharmacokinetic (PK) Parameter: Lambda_z of Ruxolitinib | Week 1 Day 7 | 0.3492 1/hr | Geometric Coefficient of Variation 31 |
Secondary
Pharmacokinetic (PK) Parameter: Plasma Concentration at Peak (Cmax) of Ruxolitinib
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).
Time frame: 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).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Ruxolitinib (RUX) | Pharmacokinetic (PK) Parameter: Plasma Concentration at Peak (Cmax) of Ruxolitinib | Week 1 Day 1 | 118 ng/mL | Geometric Coefficient of Variation 70.4 |
| Ruxolitinib (RUX) | Pharmacokinetic (PK) Parameter: Plasma Concentration at Peak (Cmax) of Ruxolitinib | Week 1 Day 7 | 129.3 ng/mL | Geometric Coefficient of Variation 76 |
Secondary
Pharmacokinetic (PK) Parameter: Racc of Ruxolitinib
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).
Time frame: 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).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ruxolitinib (RUX) | Pharmacokinetic (PK) Parameter: Racc of Ruxolitinib | 1.145 ratio | Geometric Coefficient of Variation 27.2 |
Secondary
Pharmacokinetic (PK) Parameter: T1/2 of Ruxolitinib
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).
Time frame: 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).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Ruxolitinib (RUX) | Pharmacokinetic (PK) Parameter: T1/2 of Ruxolitinib | Week 1 Day 1 | 1.93 hour (hr) | Geometric Coefficient of Variation 34.2 |
| Ruxolitinib (RUX) | Pharmacokinetic (PK) Parameter: T1/2 of Ruxolitinib | Week 1 Day 7 | 1.985 hour (hr) | Geometric Coefficient of Variation 31 |
Secondary
Pharmacokinetic (PK) Parameter: Tmax of Ruxolitinib
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).
Time frame: 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).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Ruxolitinib (RUX) | Pharmacokinetic (PK) Parameter: Tmax of Ruxolitinib | Week 1 Day 1 | 1.767 hour (hr) |
| Ruxolitinib (RUX) | Pharmacokinetic (PK) Parameter: Tmax of Ruxolitinib | Week 1 Day 7 | 1.542 hour (hr) |
Secondary
Pharmacokinetic (PK) Parameter: VzF of Ruxolitinib
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).
Time frame: 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).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Ruxolitinib (RUX) | Pharmacokinetic (PK) Parameter: VzF of Ruxolitinib | Week 1 Day 1 | 52.57 Liters (L) | Geometric Coefficient of Variation 46.4 |
| Ruxolitinib (RUX) | Pharmacokinetic (PK) Parameter: VzF of Ruxolitinib | Week 1 Day 7 | 66.76 Liters (L) | Geometric Coefficient of Variation 71.6 |
Post Hoc
All Collected Deaths
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.
Time frame: approx. 708 days (AEs), up to approx. 48 months (deaths)
Population: Clinical Database Population: all randomized patients
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ruxolitinib (RUX) | All Collected Deaths | Total Deaths | 89 Participants |
| Ruxolitinib (RUX) | All Collected Deaths | Deaths on-treatment | 43 Participants |
| Best Available Therapy (BAT) | All Collected Deaths | Total Deaths | 89 Participants |
| Best Available Therapy (BAT) | All Collected Deaths | Deaths on-treatment | 36 Participants |
| Cross-Over | All Collected Deaths | Total Deaths | 29 Participants |
| Cross-Over | All Collected Deaths | Deaths on-treatment | 19 Participants |