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Safety and Efficacy of Itacitinib in Combination With Corticosteroids for Treatment of Graft-Versus-Host Disease in Pediatric Subjects

Primary Purpose

Acute Graft-versus-host Disease

Status

Terminated

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

Itacitinib

Corticosteroids

About this trial

This is an interventional treatment trial for Acute Graft-versus-host Disease focused on measuring Acute graft-versus-host disease, GVHD, pediatric, JAK1 inhibitor, corticosteroids

Eligibility Criteria

28 Days - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

City of Hope National Medical Center
Childrens Hospital of Orange County
Children's Hospital Colorado - Center for Cancer and Blood Disorders
Nemours/A.I. duPont Hospital for Children
Nicklaus Children's Hospital
University of Minnesota Medical Center
Memorial Sloan Kettering Cancer Center
Duke University Medical Center
University Hospitals Cleveland Medical Center - Rainbow Babies and Children's Hospital
Doernbecher Children's Hospital - Division of Pediatric Hematology
Children's Hospital of Philadelphia - Center for Childhood Cancer Research
Sarah Cannon Research Institute, LLC
Vanderbilt University Medical Center
Fred Hutchinson Cancer Research Center
Centre Hospitalier Universitaire de Rennes
Hopitaux Universitaires De Strasbourg
CHU de Grenoble
CHU de Grenoble
Robert Debre Hospital
Hopitaux Universitaires De Strasbourg
CHRU Nancy
CHU Nancy
Universitaetsklinikum Aachen, AoeR
Universitatsklinikum Jena, Klinik fur Kinder und Jugendmedizin
Policlinico S. Orsola-Malpighi
Azienda Ospedaliero Unversitatia Policlinico - Vittorio Emanuele - Presido Ospedaliero G. Rodolico
Fondazione MBBM
Ospedale Pediatrico Bambino Gesu
AOU Citta della Salute e della Scienza di Torino - Ospedale Regina Margherita
Hospital Vall D Hebron
Hospital Clinico de Santiago de Compostela
Hospital Universitari i Politecnic La Fe
Birmingham Childrens Hospital
Bristol Royal Hospital for Children
Leeds Teaching Hospitals NHS Trust
Great Ormond Street Hospital for Children
Central Manchester University Hospital - Royal Manchester Children's Hospital
Royal Marsden Hospital - Surrey

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Itacitinib + Corticosteroids

Arm Description

Outcomes

Primary Outcome Measures

Phase 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs)

A TEAE was defined as an AE that began or worsened from Baseline after the first administration of study drug.

Phase 1: Cmax of Itacitinib When Administered With Corticosteroids

Cmax was defined as the maximum observed plasma concentration.

Phase 1: Cmin of Itacitinib When Administered With Corticosteroids

Cmin was defined as the minimum observed plasma concentration.

Phase 1: Tmax of Itacitinib When Administered With Corticosteroids

Tmax was defined as the time to the maximum concentration.

Phase 1: AUC of Itacitinib When Administered With Corticosteroids

AUC was defined as the area under the plasma concentration-time curve.

Phase 1: Cl/F of Itacitinib When Administered With Corticosteroids

Cl/F was defined as the apparent oral dose clearance.

Phase 2: Overall Response Rate up to Day 28

Overall response rate was defined as the number of participants demonstrating a complete response (CR), a very good partial response (VGPR), or a partial response (PR).

Secondary Outcome Measures

Phase 2: Number of Participants With TEAEs

A TEAE was defined as an AE that began or worsened from Baseline after the first administration of study drug.

Phase 2: Cmax of Itacitinib When Administered With Corticosteroids

Cmax was defined as the maximum observed plasma concentration.

Phase 2: Cmin of Itacitinib When Administered With Corticosteroids

Cmin was defined as the minimum observed plasma concentration.

Phase 2: Tmax of Itacitinib When Administered With Corticosteroids

Tmax was defined as the time to the maximum concentration.

Phase 2: AUC of Itacitinib When Administered With Corticosteroids

AUC was defined as the area under the plasma concentration-time curve.

Phase 2: Cl/F of Itacitinib When Administered With Corticosteroids

Cl/F was defined as the apparent oral dose clearance.

Phase 2: Overall Response Rate up to 100 Days

Overall response rate was defined as the number of participants demonstrating a CR, a VGPR, or a PR.

Phase 1: Overall Response Rate

Overall response rate was defined as the number of participants demonstrating a CR, a VGPR, or a PR.

Phase 2: Non Relapse Mortality

Non relapse mortality was defined as the number of participants who died due to causes other than underlying hematologic disorders relapse.

Phase 2: Duration of Response

Duration of response was defined as the time of the onset of response to the loss of response.

Phase 2: Time to Response

Time to response was defined as the interval from treatment initiation to the first response.

Phase 2: Relapse Rate of Malignant and Nonmalignant Disorders

Relapse rate was defined as the number of participants whose underlying disease relapsed.

Phase 2: Malignant and Nonmalignant Disorders Relapse-related Mortality Rate

Mortality rate was defined as the number of participants whose underlying hematologic disorder relapsed and had a fatal outcome.

Phase 2: Failure-free Survival

Failure-free survival was defined as the number of participants who were still alive, had not relapsed, had not required additional therapy for acute graft-versus-host disease (aGVHD), and had not demonstrated signs or symptoms of chronic GVHD.

Phase 2: Overall Survival

Overall survival was defined as the interval from study enrollment to death due to any cause.

Phase 2: Incidence Rate of Secondary Graft Failure

Analysis was to be conducted to assess the number of participants experiencing secondary graft failure.

Phase 2: Average Corticosteroid Use

The average number of participants who discontinued corticosteroids was to be assessed.

Phase 2: Cumulative Corticosteroid Dose

The number of participants with various cumulative corticosteroid doses was assessed.

Phase 2: Number of Participants Who Discontinued Corticosteroids

The number of participants who discontinued corticosteroids was assessed.

Phase 2: Number of Participants Who Discontinued Immunosuppressive Medication

The number of participants who discontinued immunosuppressive medication was assessed.

Phase 2: Number of Participants With aGVHD Flares

The number of participants who experienced aGVHD flares requiring treatment was assessed.

Phase 2: Number of Participants With Chronic Graft-versus-host Disease (cGVHD)

The number of participants with a diagnosis of any cGVHD, including mild, moderate, severe, was assessed.

Full Information

NCT ID

NCT03721965

First Posted

October 25, 2018

Last Updated

January 24, 2023

Sponsor

Incyte Corporation

1. Study Identification

Unique Protocol Identification Number

NCT03721965

Brief Title

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

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Terminated

Why Stopped

The study was terminated due to insufficient efficacy in a separate phase III study

Study Start Date

December 31, 2019 (Actual)

Primary Completion Date

February 17, 2020 (Actual)

Study Completion Date

February 17, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Incyte Corporation

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Graft-versus-host Disease

Keywords

Acute graft-versus-host disease, GVHD, pediatric, JAK1 inhibitor, corticosteroids

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

2 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Itacitinib + Corticosteroids

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

Itacitinib

Other Intervention Name(s)

INCB039110

Intervention Description

Phase 1: Itacitinib administered orally once daily at the protocol-defined dose according to age cohort, with dose reductions or modifications based on safety assessments. Phase 2: Itacitinib administered orally once daily at the recommended dose from Phase 1.

Intervention Type

Drug

Intervention Name(s)

Corticosteroids

Other Intervention Name(s)

prednisone, methylprednisolone

Intervention Description

Phase 1 and 2: Methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose that is appropriate for the severity of disease as outlined per local treatment guidelines as background treatment.

Primary Outcome Measure Information:

Title

Phase 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs)

Description

A TEAE was defined as an AE that began or worsened from Baseline after the first administration of study drug.

Time Frame

up to 45 days

Title

Phase 1: Cmax of Itacitinib When Administered With Corticosteroids

Description

Cmax was defined as the maximum observed plasma concentration.

Time Frame

Day 1: 1, 2, 4, and 6 hours post-dose. Day 7: predose; 1, 2, 4, and 6 hours post-dose

Title

Phase 1: Cmin of Itacitinib When Administered With Corticosteroids

Description

Cmin was defined as the minimum observed plasma concentration.

Time Frame

Day 1: 1, 2, 4, and 6 hours post-dose. Day 7: predose; 1, 2, 4, and 6 hours post-dose

Title

Phase 1: Tmax of Itacitinib When Administered With Corticosteroids

Description

Tmax was defined as the time to the maximum concentration.

Time Frame

Day 1: 1, 2, 4, and 6 hours post-dose. Day 7: predose; 1, 2, 4, and 6 hours post-dose

Title

Phase 1: AUC of Itacitinib When Administered With Corticosteroids

Description

AUC was defined as the area under the plasma concentration-time curve.

Time Frame

Day 1: 1, 2, 4, and 6 hours post-dose. Day 7: predose; 1, 2, 4, and 6 hours post-dose

Title

Phase 1: Cl/F of Itacitinib When Administered With Corticosteroids

Description

Cl/F was defined as the apparent oral dose clearance.

Time Frame

Day 1: 1, 2, 4, and 6 hours post-dose. Day 7: predose; 1, 2, 4, and 6 hours post-dose

Title

Phase 2: Overall Response Rate up to Day 28

Description

Overall response rate was defined as the number of participants demonstrating a complete response (CR), a very good partial response (VGPR), or a partial response (PR).

Time Frame

up to Day 28

Secondary Outcome Measure Information:

Title

Phase 2: Number of Participants With TEAEs

Description

A TEAE was defined as an AE that began or worsened from Baseline after the first administration of study drug.

Time Frame

up to 12 months

Title

Phase 2: Cmax of Itacitinib When Administered With Corticosteroids

Description

Cmax was defined as the maximum observed plasma concentration.

Time Frame