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

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

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.

Study Overview

• Status: Terminated
• Conditions: Acute Graft-versus-host Disease
• Intervention / Treatment: Drug: Itacitinib; Drug: Corticosteroids

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2; Phase 1

Expanded Access

No longer available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• France
  • Grenoble, France, 38043
    • Chu de Grenoble
  • Grenoble, France, 38403
    • Chu de Grenoble
  • Paris, France, 75019
    • Robert Debre Hospital
  • Strasbourg Cedex, France, 67098
    • Hôpitaux Universitaires de Strasbourg
  • Vandœuvre-lès-Nancy, France, 54500
    • CHU Nancy
  • Vandœuvre-lès-Nancy, France, 54500
    • CHRU Nancy
  • Cedex
    • Strasbourg, Cedex, France, 67098
      • Hôpitaux Universitaires de Strasbourg
  • Cedex 2
    • Rennes, Cedex 2, France, 35203
      • Centre Hospitalier Universitaire de Rennes
• Germany
  • Aachen, Germany, 52074
    • Universitaetsklinikum Aachen, AoeR
  • Jena, Germany, 07747
    • Universitatsklinikum Jena, Klinik fur Kinder und Jugendmedizin
• Italy
  • Bologna, Italy, 40138
    • Policlinico S. Orsola-Malpighi
  • Catania, Italy, 95123
    • Azienda Ospedaliero Unversitatia Policlinico - Vittorio Emanuele - Presido Ospedaliero G. Rodolico
  • Monza, Italy, 20900
    • Fondazione MBBM
  • Roma, Italy, 00165
    • Ospedale Pediatrico Bambino Gesù
  • Torino, Italy, 10126
    • AOU Citta della Salute e della Scienza di Torino - Ospedale Regina Margherita
• Spain
  • Barcelona, Spain, 08035
    • Hospital Vall D Hebron
  • Santiago De Compostela, Spain, 15706
    • Hospital Clínico de Santiago de Compostela
  • Valencia, Spain, 46026
    • Hospital Universitari i Politècnic La Fe
• United Kingdom
  • Birmingham, United Kingdom, B4 6NH
    • Birmingham Childrens Hospital
  • Bristol, United Kingdom, BS2 8BJ
    • Bristol Royal Hospital for Children
  • Leeds, United Kingdom, LS13EX
    • Leeds Teaching Hospitals NHS Trust
  • London, United Kingdom, WC1N 3JH
    • Great Ormond Street Hospital for Children
  • Manchester, United Kingdom, M13 9WL
    • Central Manchester University Hospital - Royal Manchester Children's Hospital
  • Surrey Quays, United Kingdom, SM2 5PT
    • Royal Marsden Hospital - Surrey
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope National Medical Center
    • Orange, California, United States, 92868
      • Childrens Hospital of Orange County
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado - Center for Cancer and Blood Disorders
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • Nemours/A.I. duPont Hospital for Children
  • Florida
    • Miami, Florida, United States, 33155
      • Nicklaus Children's Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55454
      • University of Minnesota Medical Center
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center - Rainbow Babies and Children's Hospital
  • Oregon
    • Portland, Oregon, United States, 97239
      • Doernbecher Children's Hospital - Division of Pediatric Hematology
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia - Center for Childhood Cancer Research
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute, LLC
    • Nashville, Tennessee, United States, 37232-6868
      • Vanderbilt University Medical Center
  • Washington
    • Seattle, Washington, United States, 98109-1024
      • Fred Hutchinson Cancer Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 weeks to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Itacitinib + Corticosteroids

Drug: Itacitinib; 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.; Other Names: INCB039110; Drug: Corticosteroids; 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.; Other Names: prednisone, methylprednisolone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	up to 45 days
Phase 1: Cmax of Itacitinib When Administered With Corticosteroids	Cmax was defined as the maximum observed plasma concentration.	Day 1: 1, 2, 4, and 6 hours post-dose. Day 7: predose; 1, 2, 4, and 6 hours post-dose
Phase 1: Cmin of Itacitinib When Administered With Corticosteroids	Cmin was defined as the minimum observed plasma concentration.	Day 1: 1, 2, 4, and 6 hours post-dose. Day 7: predose; 1, 2, 4, and 6 hours post-dose
Phase 1: Tmax of Itacitinib When Administered With Corticosteroids	Tmax was defined as the time to the maximum concentration.	Day 1: 1, 2, 4, and 6 hours post-dose. Day 7: predose; 1, 2, 4, and 6 hours post-dose
Phase 1: AUC of Itacitinib When Administered With Corticosteroids	AUC was defined as the area under the plasma concentration-time curve.	Day 1: 1, 2, 4, and 6 hours post-dose. Day 7: predose; 1, 2, 4, and 6 hours post-dose
Phase 1: Cl/F of Itacitinib When Administered With Corticosteroids	Cl/F was defined as the apparent oral dose clearance.	Day 1: 1, 2, 4, and 6 hours post-dose. Day 7: predose; 1, 2, 4, and 6 hours post-dose
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).	up to Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	up to 12 months
Phase 2: Cmax of Itacitinib When Administered With Corticosteroids	Cmax was defined as the maximum observed plasma concentration.	Day 7: predose; 1, 2, and 4 hours post-dose
Phase 2: Cmin of Itacitinib When Administered With Corticosteroids	Cmin was defined as the minimum observed plasma concentration.	Day 7: predose; 1, 2, and 4 hours post-dose
Phase 2: Tmax of Itacitinib When Administered With Corticosteroids	Tmax was defined as the time to the maximum concentration.	Day 7: predose; 1, 2, and 4 hours post-dose
Phase 2: AUC of Itacitinib When Administered With Corticosteroids	AUC was defined as the area under the plasma concentration-time curve.	Day 7: predose; 1, 2, and 4 hours post-dose
Phase 2: Cl/F of Itacitinib When Administered With Corticosteroids	Cl/F was defined as the apparent oral dose clearance.	Day 7: predose; 1, 2, and 4 hours post-dose
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.	up to 100 days
Phase 1: Overall Response Rate	Overall response rate was defined as the number of participants demonstrating a CR, a VGPR, or a PR.	up to Day 28
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.	up to 24 months
Phase 2: Duration of Response	Duration of response was defined as the time of the onset of response to the loss of response.	up to approximately 12 months
Phase 2: Time to Response	Time to response was defined as the interval from treatment initiation to the first response.	up to approximately 12 months
Phase 2: Relapse Rate of Malignant and Nonmalignant Disorders	Relapse rate was defined as the number of participants whose underlying disease relapsed.	up to approximately 12 months
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.	up to approximately 12 months
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.	up to 6 months
Phase 2: Overall Survival	Overall survival was defined as the interval from study enrollment to death due to any cause.	up to approximately 12 months
Phase 2: Incidence Rate of Secondary Graft Failure	Analysis was to be conducted to assess the number of participants experiencing secondary graft failure.	up to approximately 12 months
Phase 2: Average Corticosteroid Use	The average number of participants who discontinued corticosteroids was to be assessed.	up to 180 days
Phase 2: Cumulative Corticosteroid Dose	The number of participants with various cumulative corticosteroid doses was assessed.	up to 180 days
Phase 2: Number of Participants Who Discontinued Corticosteroids	The number of participants who discontinued corticosteroids was assessed.	up to 100 days
Phase 2: Number of Participants Who Discontinued Immunosuppressive Medication	The number of participants who discontinued immunosuppressive medication was assessed.	up to 100 days
Phase 2: Number of Participants With aGVHD Flares	The number of participants who experienced aGVHD flares requiring treatment was assessed.	up to 100 Days
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.	up to 365 days

Collaborators and Investigators

• Sponsor: Incyte Corporation

Study record dates

Study Major Dates

• Study Start (Actual): December 31, 2019
• Primary Completion (Actual): February 17, 2020
• Study Completion (Actual): February 17, 2020

Study Registration Dates

• First Submitted: October 25, 2018
• First Submitted That Met QC Criteria: October 25, 2018
• First Posted (Actual): October 26, 2018

Study Record Updates

• Last Update Posted (Estimate): February 20, 2023
• Last Update Submitted That Met QC Criteria: January 24, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: pediatric; GVHD; corticosteroids; Acute graft-versus-host disease; JAK1 inhibitor
• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Methylprednisolone; Prednisone
• Other Study ID Numbers: INCB 39110-120

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No