Clinical trial NCT03721965: Safety and Efficacy of Itacitinib in Combination With Corticosteroids for Treatment of Graft-Versus-Host Disease in Pediatric Subjects
Official title: An Open-Label, Single-Arm, Phase 1/2 Study Evaluating the Safety and Efficacy of Itacitinib in Combination With Corticosteroids for the Treatment of Steroid-Naive Acute Graft-Versus-Host Disease in Pediatric Subjects
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Acute Graft-versus-host Disease
Keywords: Acute graft-versus-host disease
GVHD
pediatric
JAK1 inhibitor
corticosteroids
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2018-10-26
Enrollment: 2
Sex: ALL
Minimum age (years): 28
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate itacitinib in combination with corticosteroids for the treatment of Grades II to IV acute graft-versus-host disease (aGVHD) in steroid-naive pediatric participants.


Eligibility criteria: Inclusion Criteria:

* Male and female participants: 12 to \< 18 years old (Cohort 1), 6 to \< 12 years old (Cohort 2), 2 to \< 6 years old (Cohort 3), Weighing \> 8 kg to \< 2 years old (Cohort 4), and 28 days old to weighing ≤ 8 kg (Cohort 5).
* Undergone 1 allogeneic hematopoietic stem cell transplantation (allo-HSCT) from any donor and source for hematological malignancies or disorders. Recipients of myeloablative and reduced-intensity conditioning regimens are eligible.
* Clinically suspected Grade II to IV aGVHD as per Mount Sinai Acute GVHD International Consortium (MAGIC) criteria, occurring after allo-HSCT and any GVHD prophylactic medication.
* Evidence of myeloid engraftment.

Exclusion Criteria:

* More than 1 allo-HSCT.
* Received more than 2 days of systemic corticosteroids for aGVHD before the first study drug administration.
* Presence of GVHD overlap syndrome.
* Presence of an active uncontrolled infection.
* Known HIV infection.
* Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection that requires treatment or at risk for HBV reactivation.
* Evidence of relapsed primary disease or have been treated for relapse after the allo-HSCT was performed.
* Any corticosteroid therapy for indications other than GVHD at doses \> 1 mg/kg once daily of methylprednisolone (or equivalent) within 7 days of the first study drug administration.
* Receipt of live (including attenuated) vaccines or anticipation of need for such vaccines during the study.
* Receipt of JAK inhibitor therapy after allo-HSCT for any indication.
* Treatment with any other investigational agent, device, or procedure within 21 days (or 5 half-lives, whichever is greater) of enrollment.

Primary outcomes:
measure: Phase 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: up to 45 days
measure: Phase 1: Cmax of Itacitinib When Administered With Corticosteroids
timeFrame: Day 1: 1, 2, 4, and 6 hours post-dose. Day 7: predose; 1, 2, 4, and 6 hours post-dose
measure: Phase 1: Cmin of Itacitinib When Administered With Corticosteroids
timeFrame: Day 1: 1, 2, 4, and 6 hours post-dose. Day 7: predose; 1, 2, 4, and 6 hours post-dose
measure: Phase 1: Tmax of Itacitinib When Administered With Corticosteroids
timeFrame: Day 1: 1, 2, 4, and 6 hours post-dose. Day 7: predose; 1, 2, 4, and 6 hours post-dose
measure: Phase 1: AUC of Itacitinib When Administered With Corticosteroids
timeFrame: Day 1: 1, 2, 4, and 6 hours post-dose. Day 7: predose; 1, 2, 4, and 6 hours post-dose
measure: Phase 1: Cl/F of Itacitinib When Administered With Corticosteroids
timeFrame: Day 1: 1, 2, 4, and 6 hours post-dose. Day 7: predose; 1, 2, 4, and 6 hours post-dose
measure: Phase 2: Overall Response Rate up to Day 28
timeFrame: up to Day 28
Secondary outcomes:
measure: Phase 2: Number of Participants With TEAEs
timeFrame: up to 12 months
measure: Phase 2: Cmax of Itacitinib When Administered With Corticosteroids
timeFrame: Day 7: predose; 1, 2, and 4 hours post-dose
measure: Phase 2: Cmin of Itacitinib When Administered With Corticosteroids
timeFrame: Day 7: predose; 1, 2, and 4 hours post-dose
measure: Phase 2: Tmax of Itacitinib When Administered With Corticosteroids
timeFrame: Day 7: predose; 1, 2, and 4 hours post-dose
measure: Phase 2: AUC of Itacitinib When Administered With Corticosteroids
timeFrame: Day 7: predose; 1, 2, and 4 hours post-dose
measure: Phase 2: Cl/F of Itacitinib When Administered With Corticosteroids
timeFrame: Day 7: predose; 1, 2, and 4 hours post-dose
measure: Phase 2: Overall Response Rate up to 100 Days
timeFrame: up to 100 days
measure: Phase 1: Overall Response Rate
timeFrame: up to Day 28
measure: Phase 2: Non Relapse Mortality
timeFrame: up to 24 months
measure: Phase 2: Duration of Response
timeFrame: up to approximately 12 months
measure: Phase 2: Time to Response
timeFrame: up to approximately 12 months
measure: Phase 2: Relapse Rate of Malignant and Nonmalignant Disorders
timeFrame: up to approximately 12 months
measure: Phase 2: Malignant and Nonmalignant Disorders Relapse-related Mortality Rate
timeFrame: up to approximately 12 months
measure: Phase 2: Failure-free Survival
timeFrame: up to 6 months
measure: Phase 2: Overall Survival
timeFrame: up to approximately 12 months
measure: Phase 2: Incidence Rate of Secondary Graft Failure
timeFrame: up to approximately 12 months
measure: Phase 2: Average Corticosteroid Use
timeFrame: up to 180 days
measure: Phase 2: Cumulative Corticosteroid Dose
timeFrame: up to 180 days
measure: Phase 2: Number of Participants Who Discontinued Corticosteroids
timeFrame: up to 100 days
measure: Phase 2: Number of Participants Who Discontinued Immunosuppressive Medication
timeFrame: up to 100 days
measure: Phase 2: Number of Participants With aGVHD Flares
timeFrame: up to 100 Days
measure: Phase 2: Number of Participants With Chronic Graft-versus-host Disease (cGVHD)
timeFrame: up to 365 days
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Orange
country: United States
facility: Childrens Hospital of Orange County
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado - Center for Cancer and Blood Disorders
state: Colorado
city: Wilmington
country: United States
facility: Nemours/A.I. duPont Hospital for Children
state: Delaware
city: Miami
country: United States
facility: Nicklaus Children's Hospital
state: Florida
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center
state: Minnesota
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center - Rainbow Babies and Children's Hospital
state: Ohio
city: Portland
country: United States
facility: Doernbecher Children's Hospital - Division of Pediatric Hematology
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia - Center for Childhood Cancer Research
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute, LLC
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Rennes
country: France
facility: Centre Hospitalier Universitaire de Rennes
state: Cedex 2
city: Strasbourg
country: France
facility: Hopitaux Universitaires De Strasbourg
state: Cedex
city: Grenoble
country: France
facility: CHU de Grenoble
city: Grenoble
country: France
facility: CHU de Grenoble
city: Paris
country: France
facility: Robert Debre Hospital
city: Strasbourg Cedex
country: France
facility: Hopitaux Universitaires De Strasbourg
city: Vandœuvre-lès-Nancy
country: France
facility: CHRU Nancy
city: Vandœuvre-lès-Nancy
country: France
facility: CHU Nancy
city: Aachen
country: Germany
facility: Universitaetsklinikum Aachen, AoeR
city: Jena
country: Germany
facility: Universitatsklinikum Jena, Klinik fur Kinder und Jugendmedizin
city: Bologna
country: Italy
facility: Policlinico S. Orsola-Malpighi
city: Catania
country: Italy
facility: Azienda Ospedaliero Unversitatia Policlinico - Vittorio Emanuele - Presido Ospedaliero G. Rodolico
city: Monza
country: Italy
facility: Fondazione MBBM
city: Roma
country: Italy
facility: Ospedale Pediatrico Bambino Gesu
city: Torino
country: Italy
facility: AOU Citta della Salute e della Scienza di Torino - Ospedale Regina Margherita
city: Barcelona
country: Spain
facility: Hospital Vall D Hebron
city: Santiago De Compostela
country: Spain
facility: Hospital Clinico de Santiago de Compostela
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
city: Birmingham
country: United Kingdom
facility: Birmingham Childrens Hospital
city: Bristol
country: United Kingdom
facility: Bristol Royal Hospital for Children
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals NHS Trust
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children
city: Manchester
country: United Kingdom
facility: Central Manchester University Hospital - Royal Manchester Children's Hospital
city: Surrey Quays
country: United Kingdom
facility: Royal Marsden Hospital - Surrey
Study officials:
affiliation: Incyte Corporation
name: Rodica Morariu-Zamfir, MD
role: STUDY_DIRECTOR
References: