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NCT02953678

A Study of Ruxolitinib in Combination With Corticosteroids for the Treatment of Steroid-Refractory Acute Graft-Versus-Host Disease (REACH-1)

Completed Phase 2 Results posted Last updated 24 November 2021
What this trial tests

Phase 2 trial testing Ruxolitinib in Graft-versus-host Disease (GVHD) in 71 participants. Completed in 14 August 2019.

Timeline
30 December 2016
Primary endpoint
31 January 2018
14 August 2019

Quick facts

Lead sponsorIncyte Corporation
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment71
Start date30 December 2016
Primary completion31 January 2018
Estimated completion14 August 2019
Sites38 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Incyte Corporation — full company profile →

Who can join

12 and older, any sex, with Graft-versus-host Disease (GVHD). Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Overall Response Rate (ORR) at Day 28 Primary · From baseline to Day 28

Defined as the percentage of participants demonstrating a complete response (CR), very good partial response (VGPR), or partial response (PR).

Responders - CR
GroupValue95% CI
Ruxolitinib in Combination With Corticosteroids19
Responders - VGPR
GroupValue95% CI
Ruxolitinib in Combination With Corticosteroids7
Responders - PR
GroupValue95% CI
Ruxolitinib in Combination With Corticosteroids13
Overall Response Rate (ORR) Secondary · From baseline to days 14, 56, and 100

Defined as the percentage of participants demonstrating a CR, VGPR, or PR.

Day 14
GroupValue95% CI
Ruxolitinib in Combination With Corticosteroids62.049.7 – 73.2
Day 56
GroupValue95% CI
Ruxolitinib in Combination With Corticosteroids36.625.5 – 48.9
Day 100
GroupValue95% CI
Ruxolitinib in Combination With Corticosteroids32.421.8 – 44.5
Nonrelapse Mortality (NRM) Secondary · From baseline to Months 6, 9, 12, and 24

Defined as the proportion of subjects who died due to causes other than malignancy relapse.

6 months
GroupValue95% CI
Ruxolitinib in Combination With Corticosteroids44.432.5 – 55.7
9 months
GroupValue95% CI
Ruxolitinib in Combination With Corticosteroids48.235.8 – 59.5
12 months
GroupValue95% CI
Ruxolitinib in Combination With Corticosteroids52.939.6 – 64.5
24 months
GroupValue95% CI
Ruxolitinib in Combination With Corticosteroids64.846.0 – 78.5
Percentage of Participants With Six-month Duration of Response (DOR) Secondary · From Baseline up to 6 months

Defined as the time from first response until graft-versus-host disease (GVHD) progression or death. DOR was assessed when all participants who were on the study completed the Day 180 visit.

GroupValue95% CI
Ruxolitinib in Combination With Corticosteroids68.249.6 – 81.2
Percentage of Participants With Three-month DOR Secondary · From Baseline up to 3 months

Defined as the time from first response until GVHD progression or death. DOR was assessed when all participants who were on the study completed the Day 84 visit.

GroupValue95% CI
Ruxolitinib in Combination With Corticosteroids84.568.7 – 92.7
Relapse Rate Secondary · From Baseline until death, withdrawal of consent, or the end of the study, whichever occurs first (up to approximately 24 months)

Defined as the percentage of participants whose underlying malignancy relapsed.

GroupValue95% CI
Ruxolitinib in Combination With Corticosteroids7.02.3 – 15.7
Relapse-related Mortality Rate Secondary · From Baseline until death, withdrawal of consent, or the end of the study, whichever occurs first (up to approximately 24 months)

Defined as the percentage of participants whose malignancy relapsed and had a fatal outcome.

GroupValue95% CI
Ruxolitinib in Combination With Corticosteroids5.61.6 – 13.8
Failure-free Survival (FFS) Secondary · From Baseline until death, withdrawal of consent, or the end of the study, whichever occurs first (up to approximately 24 months)

Defined as the time from first dose of ruxolitinib to the earliest date that a participant died, had a relapse/progression of the underlying malignancy, required additional therapy for aGVHD, or demonstrated signs or symptoms of chronic graft-versus-host disease (cGVHD).

GroupValue95% CI
Ruxolitinib in Combination With Corticosteroids85.042.0 – 158.0
Overall Survival (OS) Secondary · From Baseline until death, withdrawal of consent, or the end of the study, whichever occurs first (up to approximately 24 months)

Defined as the time from study enrollment (first day of ruxolitinib treatment) to death due to any cause.

GroupValue95% CI
Ruxolitinib in Combination With Corticosteroids232.093.0 – 675.0
Number of Participants With Treatment-emergent Adverse Events (TEAES), Serious TEAEs, And Grade 3 or Higher TEAEs Secondary · From signing the informed consent form up to 30-35 days after the last dose of study treatment (up to 24 months)

AE was any unfavorable and unintended sign, symptom, or disease temporally associated with use of medical treatment or procedure that may or may not be considered related to the medical treatment or procedure. Serious AE was any untoward medical occurrence that results in death; is life-threatening; requires inpatient hospitalization or prolongation of present hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect or is a medically important event that may not be immediately life-threatening or result in death or hospitalization. TEAE

TEAEs
GroupValue95% CI
Ruxolitinib in Combination With Corticosteroids71
Serious TEAEs
GroupValue95% CI
Ruxolitinib in Combination With Corticosteroids59
Grade 3 or Higher TEAEs
GroupValue95% CI
Ruxolitinib in Combination With Corticosteroids69

Adverse events — posted to ClinicalTrials.gov

Time frame: From signing the informed consent form up to 30-35 days after the last dose of study treatment (up to 24 months). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Ruxolitinib in Combination With Corticosteroids
Serious: 59/71 (83%)
Deaths: 46/71

Serious adverse events (101 terms)

ReactionSystemRuxolitinib in Combination…
SepsisInfections and infestations
PyrexiaGeneral disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
Lung infectionInfections and infestations
PneumoniaInfections and infestations
Pneumatosis intestinalisGastrointestinal disorders
BacteraemiaInfections and infestations
Acute kidney injuryRenal and urinary disorders
DiarrhoeaGastrointestinal disorders
Septic shockInfections and infestations
Mental status changesPsychiatric disorders
AnaemiaBlood and lymphatic system disorders
Myocardial infarctionCardiac disorders
Lower gastrointestinal haemorrhageGastrointestinal disorders
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
Multiple organ dysfunction syndromeGeneral disorders
Hepatic failureHepatobiliary disorders
Device related infectionInfections and infestations
InfluenzaInfections and infestations
Staphylococcal bacteraemiaInfections and infestations
Platelet count decreasedInvestigations
Failure to thriveMetabolism and nutrition disorders
HyponatraemiaMetabolism and nutrition disorders
Muscular weaknessMusculoskeletal and connective tissue disorders
Other adverse events (109 terms — click to expand)

ReactionSystemRuxolitinib in Combination…
AnaemiaBlood and lymphatic system disorders
HypokalaemiaMetabolism and nutrition disorders
Oedema peripheralGeneral disorders
Platelet count decreasedInvestigations
Neutrophil count decreasedInvestigations
HypomagnesaemiaMetabolism and nutrition disorders
Muscular weaknessMusculoskeletal and connective tissue disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
NauseaGastrointestinal disorders
FatigueGeneral disorders
HypocalcaemiaMetabolism and nutrition disorders
White blood cell count decreasedInvestigations
DiarrhoeaGastrointestinal disorders
HypophosphataemiaMetabolism and nutrition disorders
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
HyperglycaemiaMetabolism and nutrition disorders
VomitingGastrointestinal disorders
Decreased appetiteMetabolism and nutrition disorders
Back painMusculoskeletal and connective tissue disorders
HypertensionVascular disorders
Abdominal painGastrointestinal disorders
CoughRespiratory, thoracic and mediastinal disorders
Sinus tachycardiaCardiac disorders
FallInjury, poisoning and procedural complications
HypotensionVascular disorders
ThrombocytopeniaBlood and lymphatic system disorders
ConstipationGastrointestinal disorders
Blood creatinine increasedInvestigations
HypoalbuminaemiaMetabolism and nutrition disorders
HyponatraemiaMetabolism and nutrition disorders
ArthralgiaMusculoskeletal and connective tissue disorders
HeadacheNervous system disorders
Acute kidney injuryRenal and urinary disorders
Pain in extremityMusculoskeletal and connective tissue disorders
HaematuriaRenal and urinary disorders
Dry eyeEye disorders
Abdominal distensionGastrointestinal disorders
Dry mouthGastrointestinal disorders
FlatulenceGastrointestinal disorders

Most-reported serious reactions: Sepsis, Pyrexia, Respiratory failure, Lung infection, Pneumonia, Pneumatosis intestinalis, Bacteraemia, Acute kidney injury.

Data from ClinicalTrials.gov NCT02953678 adverse events section.

Sponsor's own description

The purpose of this study was to assess the efficacy of ruxolitinib in combination with corticosteroids in subjects with Grades II to IV steroid-refractory acute graft-versus-host disease (GVHD).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. JAK inhibition as a therapeutic strategy for immune and inflammatory diseases.
    Schwartz DM, Kanno Y, Villarino A, Ward M, et al · · 2017 · cited 308× · PMID 29282366 · DOI 10.1038/nrd.2017.267
  2. Signal Transducer and Activator of Transcription (STATs) Proteins in Cancer and Inflammation: Functions and Therapeutic Implication.
    Loh CY, Arya A, Naema AF, Wong WF, et al · · 2019 · cited 241× · PMID 30847297 · DOI 10.3389/fonc.2019.00048
  3. Ruxolitinib for the treatment of steroid-refractory acute GVHD (REACH1): a multicenter, open-label phase 2 trial.
    Jagasia M, Perales MA, Schroeder MA, Ali H, et al · · 2020 · cited 214× · PMID 32160294 · DOI 10.1182/blood.2020004823
  4. Emerging Topical and Systemic JAK Inhibitors in Dermatology.
    Solimani F, Meier K, Ghoreschi K. · · 2019 · cited 199× · PMID 31849996 · DOI 10.3389/fimmu.2019.02847
  5. FDA Approval Summary: Ruxolitinib for Treatment of Steroid-Refractory Acute Graft-Versus-Host Disease.
    Przepiorka D, Luo L, Subramaniam S, Qiu J, et al · · 2020 · cited 100× · PMID 32043777 · DOI 10.1634/theoncologist.2019-0627
  6. Treatment and unmet needs in steroid-refractory acute graft-versus-host disease.
    Malard F, Huang XJ, Sim JPY. · · 2020 · cited 98× · PMID 32242050 · DOI 10.1038/s41375-020-0804-2
  7. The Role of Janus Kinase Signaling in Graft-Versus-Host Disease and Graft Versus Leukemia.
    Schroeder MA, Choi J, Staser K, DiPersio JF. · · 2018 · cited 82× · PMID 29289756 · DOI 10.1016/j.bbmt.2017.12.797
  8. New and emerging therapies for acute and chronic graft <i>versus</i> host disease.
    Hill L, Alousi A, Kebriaei P, Mehta R, et al · · 2018 · cited 81× · PMID 29317998 · DOI 10.1177/2040620717741860

Verify or expand the search:

Other trials of Ruxolitinib

Trials testing the same drug.

Other recruiting trials for Graft-versus-host Disease (GVHD)

Currently open trials in the same condition.

Other Incyte Corporation trials

Trials by the same sponsor.

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