A Study of Ruxolitinib vs Best Available Therapy (BAT) in Patients With Steroid-refractory Chronic Graft vs. Host Disease (GvHD) After Bone Marrow Transplantation (REACH3)

Graft-versus-host Disease (GVHD) Clinical Trial

Official title:

A Phase III Randomized Open-label Multi-center Study of Ruxolitinib vs. Best Available Therapy in Patients With Corticosteroid-refractory Chronic Graft vs Host Disease After Allogeneic Stem Cell Transplantation (REACH3)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03112603
• Other study ID #: INCB 18424-365 (REACH3)
• Secondary ID: CINC424D2301
• Status: Completed
• Phase: Phase 3
• Start date: June 29, 2017
• Est. completion date: December 15, 2022

Study information

• Verified date: July 2023
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the efficacy of ruxolitinib against best available therapy in participants with steroid-refractory chronic graft-versus-host disease (SR cGvHD).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 330
• Est. completion date: December 15, 2022
• Est. primary completion date: May 8, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

• Have undergone allogeneic stem cell transplantation (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
• Evident myeloid and platelet engraftment: Absolute neutrophil count (ANC) > 1000/mm^3 and platelet count > 25,000/ mm^3
• Participants with clinically diagnosed moderate to severe cGvHD according to NIH

Consensus Criteria prior to randomization:

• Moderate cGvHD: At least one organ (not lung) with a score of 2, 3 or more organs involved with a score of 1 in each organ, or lung score of 1
• Severe cGvHD: at least 1 organ with a score of 3, or lung score of 2 or 3
• Participants currently receiving systemic or topical corticosteroids for the treatment of cGvHD for a duration of < 12 months prior to Cycle 1 Day 1 (if applicable), and have a confirmed diagnosis of steroid-refractory cGvHD defined per 2014 NIH consensus criteria irrespective of the concomitant use of a calcineurin inhibitor (CNI), as

follows:

• A lack of response or disease progression after administration of minimum prednisone 1 mg/kg/day for at least 1 week, OR
• Disease persistence without improvement despite continued treatment with prednisone at > 0.5 mg/kg/day or 1 mg/kg/every other day for at least 4 weeks, OR
• Increase to prednisolone dose to > 0.25 mg/kg/day after 2 unsuccessful attempts to taper the dose
• Participant must accept to be treated with only one of the following BAT options on Cycle 1 Day 1 (additions and changes are allowed during the course of the study, but only with BAT from the following BAT options): extracorporeal photopheresis (ECP), low-dose methotrexate (MTX), mycophenolate mofetil (MMF), mTOR inhibitors (everolimus or sirolimus), infliximab, rituximab, pentostatin, imatinib, ibrutinib

Exclusion Criteria:

• Participants who have received 2 or more systemic treatment for cGvHD in addition to corticosteroids ± CNI for cGvHD
• Patients that transition from active aGvHD to cGvHD without tapering off corticosteroids ± CNI and any systemic treatment
• Patients receiving up to 30 mg by mouth once a day of hydrocortisone (i.e., physiologic replacement dose) of corticosteroids are allowed.
• Participants who were treated with prior JAK inhibitors for aGvHD; except when the participant achieved complete or partial response and has been off JAK inhibitor treatment for at least 8 weeks prior to Cycle 1 Day 1
• Failed prior alloSCT within the past 6 months from Cycle 1 Day 1
• Participants with relapsed primary malignancy, or who have been treated for relapse after the alloSCT was performed
• Steroid refractory cGvHD occurring after a non-scheduled donor lymphocyte infusion (DLI) administered for preemptive treatment of malignancy recurrence. Participants who have received a scheduled DLI as part of their transplant procedure and not for management of malignancy relapse are eligible
• Any corticosteroid therapy for indications other than cGvHD at doses > 1 mg/kg/day methylprednisolone or equivalent within 7 days of Cycle 1 Day 1

Related Conditions & MeSH terms

• Graft vs Host Disease
• Graft-versus-host Disease (GVHD)

Intervention

Drug:
• Ruxolitinib
Ruxolitinib twice daily at the protocol-defined starting dose.
• Extracorporeal photopheresis (ECP)
Best available therapy (BAT) will be selected by the investigator for each participant. BAT may not include experimental agents (ie, those not approved for the treatment of any indication) as well as a limited number of other selected drugs in accordance with the protocol-defined requirements. The BAT in this study will be among the following treatments currently used in this setting (no other types or combinations of BATs are permitted in this study).
• Low-dose methotrexate (MTX)
Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
• Mycophenolate mofetil (MMF)
Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
• mechanistic Target of Rapamycin (mTOR) inhibitors (everolimus or sirolimus)
Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
• Infliximab
Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
• Rituximab
Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
• Pentostatin
Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
• Imatinib
Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
• Ibrutinib
Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Darlinghurst	New South Wales
Australia	Novartis Investigative Site	Parkville	Victoria
Austria	Novartis Investigative Site	Graz
Austria	Novartis Investigative Site	Innsbruck	Tyrol
Austria	Novartis Investigative Site	Linz
Austria	Novartis Investigative Site	Vienna
Belgium	Novartis Investigative Site	Antwerpen
Belgium	Novartis Investigative Site	Brugge
Belgium	Novartis Investigative Site	Bruxelles
Belgium	Novartis Investigative Site	Gent
Belgium	Novartis Investigative Site	Leuven
Belgium	Novartis Investigative Site	Liege
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Canada	Novartis Investigative Site	Hamilton	Ontario
Canada	Novartis Investigative Site	Ottawa	Ontario
Canada	Novartis Investigative Site	Toronto	Ontario
Canada	Novartis Investigative Site	Vancouver	British Columbia
Czechia	Novartis Investigative Site	Hradec Kralove	CZE
Czechia	Novartis Investigative Site	Praha 2	Czech Republic
Czechia	Novartis Investigative Site	Praha 5
Denmark	Novartis Investigative Site	Copenhagen
Denmark	Novartis Investigative Site	Odense
France	Novartis Investigative Site	Amiens cedex1
France	Novartis Investigative Site	Bordeaux	Aquitaine
France	Novartis Investigative Site	Caen Cedex 9
France	Novartis Investigative Site	Lille Cedex
France	Novartis Investigative Site	Limoges cedex
France	Novartis Investigative Site	Lyon Cedex 08
France	Novartis Investigative Site	Montpellier cedex 5
France	Novartis Investigative Site	Paris cedex 10
France	Novartis Investigative Site	PARIS Cedex 12
France	Novartis Investigative Site	Paris Cedex 19
France	Novartis Investigative Site	Pierre-Benite Cédex
France	Novartis Investigative Site	Rennes Cedex 9
France	Novartis Investigative Site	Rouen Cedex 1
France	Novartis Investigative Site	Saint Priest en Jarez Cedex
France	Novartis Investigative Site	Strasbourg Cedex
France	Novartis Investigative Site	Toulouse Cedex 9
France	Novartis Investigative Site	Vandoeuvre les Nancy cedex
Germany	Novartis Investigative Site	Augsburg
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Duesseldorf
Germany	Novartis Investigative Site	Erlangen
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Freiburg
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Jena
Germany	Novartis Investigative Site	Kiel
Germany	Novartis Investigative Site	Koeln
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Mainz
Germany	Novartis Investigative Site	Mannheim
Germany	Novartis Investigative Site	Mannheim	Baden-Württemberg
Germany	Novartis Investigative Site	Muenster
Germany	Novartis Investigative Site	Ulm
Germany	Novartis Investigative Site	Würzburg
Greece	Novartis Investigative Site	Athens	GR
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Patras	GR
Greece	Novartis Investigative Site	Thessaloníki	GR
Hungary	Novartis Investigative Site	Budapest
India	Novartis Investigative Site	Delhi
India	Novartis Investigative Site	Navi Mumbai	Maharashtra
India	Novartis Investigative Site	Pune	Maharashtra
India	Novartis Investigative Site	Vellore
Israel	Novartis Investigative Site	Haifa
Israel	Novartis Investigative Site	Jerusalem
Israel	Novartis Investigative Site	Petach Tikva
Israel	Novartis Investigative Site	Tel Aviv
Italy	Novartis Investigative Site	Ancona	AN
Italy	Novartis Investigative Site	Bergamo	BG
Italy	Novartis Investigative Site	Bologna	BO
Italy	Novartis Investigative Site	Brescia	BS
Italy	Novartis Investigative Site	Genova	GE
Italy	Novartis Investigative Site	Genova	GE
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Palermo	PA
Italy	Novartis Investigative Site	Parma	PR
Italy	Novartis Investigative Site	Pavia	PV
Italy	Novartis Investigative Site	Perugia
Italy	Novartis Investigative Site	Pescara	PE
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Rozzano	MI
Italy	Novartis Investigative Site	Torino	TO
Italy	Novartis Investigative Site	Udine	UD
Japan	Novartis Investigative Site	Bunkyo-ku	Tokyo
Japan	Novartis Investigative Site	Fukuoka-city	Fukuoka
Japan	Novartis Investigative Site	Isehara-city	Kanagawa
Japan	Novartis Investigative Site	Kobe-city	Hyogo
Japan	Novartis Investigative Site	Kyoto
Japan	Novartis Investigative Site	Minato-ku	Tokyo
Japan	Novartis Investigative Site	Nagoya-city	Aichi
Japan	Novartis Investigative Site	Nishinomiya-city	Hyogo
Japan	Novartis Investigative Site	Okayama
Japan	Novartis Investigative Site	Osaka-city	Osaka
Japan	Novartis Investigative Site	Sapporo-city	Hokkaido
Japan	Novartis Investigative Site	Sendai-city	Miyagi
Japan	Novartis Investigative Site	Shimotsuke-city	Tochigi
Japan	Novartis Investigative Site	Shinjuku-ku	Tokyo
Japan	Novartis Investigative Site	Suita-city	Osaka
Jordan	Novartis Investigative Site	Amman
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Netherlands	Novartis Investigative Site	Leiden
Netherlands	Novartis Investigative Site	Nijmegen
Netherlands	Novartis Investigative Site	Rotterdam
Netherlands	Novartis Investigative Site	Utrecht	The Netherlands
Norway	Novartis Investigative Site	Oslo
Poland	Novartis Investigative Site	Gliwice	Slaskie
Poland	Novartis Investigative Site	Katowice
Poland	Novartis Investigative Site	Kraków
Poland	Novartis Investigative Site	Warszawa
Poland	Novartis Investigative Site	Wroclaw	Dolnoslaskie
Portugal	Novartis Investigational Site	Lisboa
Portugal	Novartis Investigative Site	Porto
Puerto Rico	Incyte Investigative Site	Ponce
Romania	Novartis Investigational Site	Bucharest
Romania	Novartis Investigational Site	Bucharest
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Saint Petersburg
Saudi Arabia	Novartis Investigative Site	Riyadh
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Cordoba	Andalucia
Spain	Novartis Investigative Site	El Palmar	Murica
Spain	Novartis Investigative Site	L'Hospitalet de Llobregat	Cataluña
Spain	Novartis Investigative Site	Las Palmas de Gran Canaria
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Salamanca	Castilla Y Leon
Spain	Novartis Investigative Site	San Sebastian	Pais Vasco
Spain	Novartis Investigative Site	Santiago de Compostela	Galicia
Spain	Novartis Investigative Site	Sevilla	Andalucía
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Sweden	Novartis Investigative Site	Göteborg
Sweden	Novartis Investigative Site	Uppsala
Switzerland	Novartis Investigative Site	Basel
Switzerland	Novartis Investigative Site	Zürich
Turkey	Novartis Investigative Site	Ankara
Turkey	Novartis Investigative Site	Ankara
Turkey	Novartis Investigative Site	Antalya
United Kingdom	Novartis Investigative Site	Glasgow
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Manchester
United States	Incyte Investigative Site	Boston	Massachusetts
United States	Incyte Investigative Site	Boston	Massachusetts
United States	Incyte Investigative Site	Chapel Hill	North Carolina
United States	Incyte Investigative Site	Chicago	Illinois
United States	Incyte Investigative Site	Chicago	Illinois
United States	Incyte Investigative Site	Chicago	Illinois
United States	Incyte Investigative Site	Cincinnati	Ohio
United States	Incyte Investigative Site	Cleveland	Ohio
United States	Incyte Investigative Site	Cleveland	Ohio
United States	Incyte Investigative Site	Columbus	Ohio
United States	Incyte Investigative Site	Dallas	Texas
United States	Incyte Investigative Site	Duarte	California
United States	Incyte Investigative Site	Durham	North Carolina
United States	Incyte Investigative Site	Gainesville	Florida
United States	Incyte Investigative Site	Hackensack	New Jersey
United States	Incyte Investigative Site	Houston	Texas
United States	Incyte Investigative Site	Indianapolis	Indiana
United States	Incyte Investigative Site	La Jolla	California
United States	Incyte Investigative Site	Lexington	Kentucky
United States	Incyte Investigative Site	Los Angeles	California
United States	Incyte Investigative Site	Maywood	Illinois
United States	Incyte Investigative Site	Milwaukee	Wisconsin
United States	Incyte Investigative Site	Nashville	Tennessee
United States	Incyte Investigative Site	New Haven	Connecticut
United States	Incyte Investigative Site	New York	New York
United States	Incyte Investigative Site	New York	New York
United States	Incyte Investigative Site	New York	New York
United States	Incyte Investigative Site	Oklahoma City	Oklahoma
United States	Incyte Investigative Site	Omaha	Nebraska
United States	Incyte Investigative Site	Philadelphia	Pennsylvania
United States	Incyte Investigative Site	Pittsburgh	Pennsylvania
United States	Incyte Investigative Site	Pittsburgh	Pennsylvania
United States	Incyte Investigative Site	Seattle	Washington
United States	Incyte Investigative Site	Tampa	Florida
United States	Incyte Investigative Site	Tucson	Arizona
United States	Incyte Investigative Site	Westwood	Kansas
United States	Incyte Investigative Site	Wilmington	Delaware
United States	Incyte Investigative Site	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Bulgaria,  Canada,  Czechia,  Denmark,  France,  Germany,  Greece,  Hungary,  India,  Israel,  Italy,  Japan,  Jordan,  Korea, Republic of,  Netherlands,  Norway,  Poland,  Portugal,  Puerto Rico,  Romania,  Russian Federation,  Saudi Arabia,  Spain,  Sweden,  Switzerland,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy of Ruxolitinib Versus Investigator's Choice Best Available Therapy (BAT) in Participants With Moderate or Severe Steroid Refractory Chronic Graft Versus Host Disease (SR-cGvHD) Assessed by Overall Response Rate (ORR) at the Cycle 7 Day 1 Visit	ORR was defined as the percentage of participants in each arm demonstrating a complete response (CR) or partial response (PR) based on chronic GvHD (cGvHD) disease assessments (National Institutes of Health Consensus Criteria) without the requirement of additional systemic therapies for an earlier progression, mixed response, or non-response. Scoring of response was relative to the organ score at the time of randomization. CR: complete resolution of all signs and symptoms of cGVHD in all evaluable organs without the initiation or addition of new systemic therapy. PR: improvement in at least one organ (e.g., improvement of 1 or more points on a 4- to 7-point scale, or an improvement of 2 or more points on a 10- to 12-point scale) without progression in other organs or sites, initiation, or addition of new systemic therapies.	Cycle 7 Day 1 (each cycle was comprised of 4 weeks)
Secondary	Rate of Participants With Clinically Relevant Improvement of the Modified Lee cGvHD Symptom Scale Score	To assess improvement of symptoms based on the total symptom score (TSS); a responder was defined as having achieved a clinically relevant reduction from Baseline of the TSS. The scale consists of 30 items in 7 subscales (skin, eye, mouth, lung, nutrition, energy, and psychological). Participants reported their level of symptom "bother" over the previous month on a 5-point likert scale: not at all, slightly, moderately, quite a bit, or extremely. Subscale scores and the summary score range from 0 to 100, with a higher score indicating worse symptoms.	Baseline; Cycle 7 Day 1 (each cycle was comprised of 4 weeks)
Secondary	Rate of Failure-free Survival (FFS)	Composite time to event endpoint incorporating the following FFS events: (i) relapse or recurrence of underlying disease or death due to underlying disease, (ii) nonrelapse mortality, or (iii) addition or initiation of another systemic therapy for cGvHD.	Baseline to when the last participant reached Cycle 7 Day 1 (each cycle was comprised of 4 weeks)
Secondary	Rate of FFS at Study Completion	Composite time to event endpoint incorporating the following FFS events: (i) relapse or recurrence of underlying disease or death due to underlying disease, (ii) nonrelapse mortality, or (iii) addition or initiation of another systemic therapy for cGvHD.	From Baseline to Last Participant Last Visit (LPLV) (approximately 5 years)
Secondary	Best Overall Response (BOR) at Cycle 7 Day 1	BOR was defined as the percentage of participants who achieved an overall response (CR+PR) based on cGvHD disease assessments (National Institutes of Health Consensus Criteria) without the requirement of additional systemic therapies for an earlier progression, mixed response, or non-response at any time point (up to Cycle 7 Day 1 or the start of additional systemic therapy for cGvHD). Scoring of response was relative to the organ score at the time of randomization. CR: complete resolution of all signs and symptoms of cGVHD in all evaluable organs without the initiation or addition of new systemic therapy. PR: improvement in at least one organ (e.g., improvement of 1 or more points on a 4- to 7-point scale, or an improvement of 2 or more points on a 10- to 12-point scale) without progression in other organs or sites, initiation, or addition of new systemic therapies. This analysis was based on the primary cutoff date (May 2020).	up to Cycle 7 Day 1 (each cycle was comprised of 4 weeks)
Secondary	BOR During Cross-over Treatment With Ruxolitinib	BOR was defined as the percentage of participants who achieved an overall response (CR+PR) based on cGvHD disease assessments (National Institutes of Health Consensus Criteria) without the requirement of additional systemic therapies for an earlier progression, mixed response, or non-response at any time point (up to Cycle 7 Day 1 or the start of additional systemic therapy for cGvHD). Scoring of response was relative to the organ score at the time of randomization. CR: complete resolution of all signs and symptoms of cGVHD in all evaluable organs without the initiation or addition of new systemic therapy. PR: improvement in at least one organ (e.g., improvement of 1 or more points on a 4- to 7-point scale, or an improvement of 2 or more points on a 10- to 12-point scale) without progression in other organs or sites, initiation, or addition of new systemic therapies.	from Crossover Cycle 1 Day 1 to any time point up to and including Crossover Cycle 7 Day 1 (each cycle was comprised of 4 weeks)
Secondary	ORR at the End of Cycle 3	ORR was defined as the percentage of participants in each arm demonstrating a CR or PR based on cGvHD disease assessments (National Institutes of Health Consensus Criteria) without the requirement of additional systemic therapies for an earlier progression, mixed response, or non-response. Scoring of response was relative to the organ score at the time of randomization. CR: complete resolution of all signs and symptoms of cGVHD in all evaluable organs without the initiation or addition of new systemic therapy. PR: improvement in at least one organ (e.g., improvement of 1 or more points on a 4- to 7-point scale, or an improvement of 2 or more points on a 10- to 12-point scale) without progression in other organs or sites, initiation, or addition of new systemic therapies.	Cycle 4 Day 1 (each cycle was comprised of 4 weeks)
Secondary	Duration of Response Through Study Completion	DOR was defined as the time from first response until cGvHD progression, death, or the date of change/addition of systemic therapies for cGvHD and as assessed for responders only. Response was based on cGvHD disease assessments (National Institutes of Health consensus criteria). Duration of response was evaluated in participants who achieved a CR or PR at or before Cycle 7 Day 1. The analysis included a larger number of participants than the number of participants who achieved CR or PR at Cycle 7 Day 1 (82 ruxolitinib and 42 BAT) because the analysis took into account not only those participants who achieved CR or PR at Cycle 7 Day 1, but also participants who achieved CR or PR before Cycle 7 Day 1 but who may have lost their response at Cycle 7 Day 1. For this reason, the number of participants in this analysis does not align with the best overall response (BOR) at Cycle 7 Day 1. This analysis was based on the cutoff date upon study completion (December 2022).	from first response to LPLV (approximately 5 years)
Secondary	Overall Survival (OS)	Overall survival was defined as the time from the date of randomization to the date of death due to any cause.	from the date of randomization to the date of death due to any cause up to LPLV (approximately 5 years)
Secondary	Cumulative Incidence of Non-relapse Mortality (NRM)	Defined as the cumulative incidence rate from competing risk analysis for NRM from the date of randomization to the date of death not preceded by underlying disease relapse/recurrence.	Months 3, 6, 12, 18, 24, 30, and 36
Secondary	Percentage of Participants With a = 50% Reduction in Daily Corticosteroid Dose	All corticosteroid dosages prescribed to the participant and all dose changes during the study were to be recorded for assessment of participants with a = 50% reduction in daily corticosteroid dose.	from Day 15 up to Day 182
Secondary	Percentage of Participants Successfully Tapered Off of All Corticosteroids	All corticosteroid dosages prescribed to the participant and all dose changes during the study were to be recorded for assessment of participants who successfully tapered off of all corticosteroids. Participants who completely tapered off corticosteroids refer to those who permanently discontinued steroids as per the dose administration panel and who did not restart steroids in the same interval. Participants who were tapered off and continued follow-up were also counted as being tapered off with 0 dose in subsequent intervals until they discontinued from the main treatment period or restarted steroid treatment.	up to Day 179
Secondary	Cumulative Incidence of Malignancy Relapse/Recurrence (MR)	Defined as the cumulative incidence rate from competing risk analysis of MR from the date of randomization to hematologic malignancy relapse/recurrence.	Months 3, 6, 12, 18, 24, 30, and 36
Secondary	Change From Baseline in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT)	Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The 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 participants. The questions were based on a 5-point Likert scale, where 0 corresponds to "not at all" and 4 corresponds to "very much." The higher the final score, the better the quality of life. The FACT-BMT total score ranges from 0 to 148.	Baseline; up to Cycle 39 Day 1 (each cycle was comprised of 4 weeks)
Secondary	Change From Baseline in EQ-5D-5L	The EQ-5D-5L is a descriptive classification consisting of five dimensions of health: mobility, self-care, usual activities, anxiety/depression, and pain/discomfort. The five-level version (no problems, slight problems, moderate problems, severe problems, and extreme problems) uses a 5-point Likert scale, with 1 being no problems and 5 being extreme problems.	Baseline; up to Cycle 39 Day 1 (each cycle was comprised of 4 weeks)
Secondary	Number of Participants With Any Treatment-emergent Adverse Event (TEAE)	Adverse events were defined as the appearance of (or worsening of any pre-existing) undesirable signs, symptoms, or medical conditions that occurred after the participant's signed informed consent was obtained. Abnormal laboratory values or test results occurring after informed consent constituted adverse events only if they induced clinical signs or symptoms, were considered clinically significant, required therapy (e.g., hematologic abnormality that required transfusion or hematological stem cell support), or required changes in study medication(s). TEAEs were defined as those AEs that started or worsened during the on-treatment period (either randomized or cross-over period).	from Baseline to LPLV (approximately 5 years)
Secondary	Cmax of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses	Cmax was defined as the maximum observed plasma concentration of ruxolitinib. Early enrolling participants (approximately the first 8 adult and first 4 adolescent participants) randomized to ruxolitinib arm followed an "extensive PK" sampling schedule. Subsequent participants randomized to ruxolitinib, any randomized participants receiving ruxolitinib after Cycle 6, and any randomized participants receiving BAT that cross over to ruxolitinib followed the "sparse PK" sampling schedule.	Extensive Sampling Schedule: Cycle 1 Days 1 and 15: predose; 0.5, 1, 1.5, 4, 6, and 9 hours post-dose. Sparse Sampling Schedule: Cycle 1 Days 1 and 15: predose; 1.5 hours post-dose
Secondary	AUClast of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses	AUClast was defined as the area under the concentration-time curve up to the last measurable concentration of ruxolitinib. Early enrolling participants (approximately the first 8 adult and first 4 adolescent participants) randomized to ruxolitinib arm followed an "extensive PK" sampling schedule. Subsequent participants randomized to ruxolitinib, any randomized participants receiving ruxolitinib after Cycle 6, and any randomized participants receiving BAT that cross over to ruxolitinib followed the "sparse PK" sampling schedule.	Extensive Sampling Schedule: Cycle 1 Days 1 and 15: predose; 0.5, 1, 1.5, 4, 6, and 9 hours post-dose. Sparse Sampling Schedule: Cycle 1 Days 1 and 15: predose; 1.5 hours post-dose
Secondary	AUCinf of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses	AUCinf was defined as the area under the concentration-time curve from time 0 to infinity. Early enrolling participants (approximately the first 8 adult and first 4 adolescent participants) randomized to ruxolitinib arm followed an "extensive PK" sampling schedule. Subsequent participants randomized to ruxolitinib, any randomized participants receiving ruxolitinib after Cycle 6, and any randomized participants receiving BAT that cross over to ruxolitinib followed the "sparse PK" sampling schedule.	Extensive Sampling Schedule: Cycle 1 Days 1 and 15: predose; 0.5, 1, 1.5, 4, 6, and 9 hours post-dose. Sparse Sampling Schedule: Cycle 1 Days 1 and 15: predose; 1.5 hours post-dose
Secondary	CL/F of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses	CL/F was defined as the oral dose clearance of ruxolitinib. Early enrolling participants (approximately the first 8 adult and first 4 adolescent participants) randomized to ruxolitinib arm followed an "extensive PK" sampling schedule. Subsequent participants randomized to ruxolitinib, any randomized participants receiving ruxolitinib after Cycle 6, and any randomized participants receiving BAT that cross over to ruxolitinib followed the "sparse PK" sampling schedule.	Extensive Sampling Schedule: Cycle 1 Days 1 and 15: predose; 0.5, 1, 1.5, 4, 6, and 9 hours post-dose. Sparse Sampling Schedule: Cycle 1 Days 1 and 15: predose; 1.5 hours post-dose
Secondary	Vz/F of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses	Vz/F was defined as the apparent oral dose volume of distribution of ruxolitinib. Early enrolling participants (approximately the first 8 adult and first 4 adolescent participants) randomized to ruxolitinib arm followed an "extensive PK" sampling schedule. Subsequent participants randomized to ruxolitinib, any randomized participants receiving ruxolitinib after Cycle 6, and any randomized participants receiving BAT that cross over to ruxolitinib followed the "sparse PK" sampling schedule.	Extensive Sampling Schedule: Cycle 1 Days 1 and 15: predose; 0.5, 1, 1.5, 4, 6, and 9 hours post-dose. Sparse Sampling Schedule: Cycle 1 Days 1 and 15: predose; 1.5 hours post-dose
Secondary	Tmax of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses	tmax was defined as the time to reach the maximum plasma concentration of ruxolitinib. Early enrolling participants (approximately the first 8 adult and first 4 adolescent participants) randomized to ruxolitinib arm followed an "extensive PK" sampling schedule. Subsequent participants randomized to ruxolitinib, any randomized participants receiving ruxolitinib after Cycle 6, and any randomized participants receiving BAT that cross over to ruxolitinib followed the "sparse PK" sampling schedule.	Extensive Sampling Schedule: Cycle 1 Days 1 and 15: predose; 0.5, 1, 1.5, 4, 6, and 9 hours post-dose. Sparse Sampling Schedule: Cycle 1 Days 1 and 15: predose; 1.5 hours post-dose
Secondary	t1/2 of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses	t1/2 was defined as the apparent terminal phase disposition half-life of ruxolitinib. Early enrolling participants (approximately the first 8 adult and first 4 adolescent participants) randomized to ruxolitinib arm followed an "extensive PK" sampling schedule. Subsequent participants randomized to ruxolitinib, any randomized participants receiving ruxolitinib after Cycle 6, and any randomized participants receiving BAT that cross over to ruxolitinib followed the "sparse PK" sampling schedule.	Extensive Sampling Schedule: Cycle 1 Days 1 and 15: predose; 0.5, 1, 1.5, 4, 6, and 9 hours post-dose. Sparse Sampling Schedule: Cycle 1 Days 1 and 15: predose; 1.5 hours post-dose
Secondary	Utilization of Medical Resources	The percentage of participants with at least one submission to healthcare encounter was assessed.	from Baseline to LPLV (approximately 5 years)