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

Acute Graft-versus-host Disease Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03721965
• Other study ID #: INCB 39110-120
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: December 31, 2019
• Est. completion date: February 17, 2020

Study information

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

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: February 17, 2020
• Est. primary completion date: February 17, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 28 Days to 18 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Graft-versus-host Disease
• Graft vs Host Disease

Intervention

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.
• 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.

Locations

Country	Name	City	State
France	CHU de Grenoble	Grenoble
France	CHU de Grenoble	Grenoble
France	Robert Debre Hospital	Paris
France	Centre Hospitalier Universitaire de Rennes	Rennes	Cedex 2
France	Hopitaux Universitaires De Strasbourg	Strasbourg	Cedex
France	Hopitaux Universitaires De Strasbourg	Strasbourg Cedex
France	CHRU Nancy	Vandœuvre-lès-Nancy
France	CHU Nancy	Vandœuvre-lès-Nancy
Germany	Universitaetsklinikum Aachen, AoeR	Aachen
Germany	Universitatsklinikum Jena, Klinik fur Kinder und Jugendmedizin	Jena
Italy	Policlinico S. Orsola-Malpighi	Bologna
Italy	Azienda Ospedaliero Unversitatia Policlinico - Vittorio Emanuele - Presido Ospedaliero G. Rodolico	Catania
Italy	Fondazione MBBM	Monza
Italy	Ospedale Pediatrico Bambino Gesu	Roma
Italy	AOU Citta della Salute e della Scienza di Torino - Ospedale Regina Margherita	Torino
Spain	Hospital Vall D Hebron	Barcelona
Spain	Hospital Clinico de Santiago de Compostela	Santiago De Compostela
Spain	Hospital Universitari i Politecnic La Fe	Valencia
United Kingdom	Birmingham Childrens Hospital	Birmingham
United Kingdom	Bristol Royal Hospital for Children	Bristol
United Kingdom	Leeds Teaching Hospitals NHS Trust	Leeds
United Kingdom	Great Ormond Street Hospital for Children	London
United Kingdom	Central Manchester University Hospital - Royal Manchester Children's Hospital	Manchester
United Kingdom	Royal Marsden Hospital - Surrey	Surrey Quays
United States	Children's Hospital Colorado - Center for Cancer and Blood Disorders	Aurora	Colorado
United States	University Hospitals Cleveland Medical Center - Rainbow Babies and Children's Hospital	Cleveland	Ohio
United States	City of Hope National Medical Center	Duarte	California
United States	Duke University Medical Center	Durham	North Carolina
United States	Nicklaus Children's Hospital	Miami	Florida
United States	University of Minnesota Medical Center	Minneapolis	Minnesota
United States	Sarah Cannon Research Institute, LLC	Nashville	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Childrens Hospital of Orange County	Orange	California
United States	Children's Hospital of Philadelphia - Center for Childhood Cancer Research	Philadelphia	Pennsylvania
United States	Doernbecher Children's Hospital - Division of Pediatric Hematology	Portland	Oregon
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Nemours/A.I. duPont Hospital for Children	Wilmington	Delaware

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Countries where clinical trial is conducted

United States,  France,  Germany,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Phase 2: Average Corticosteroid Use	The average number of participants who discontinued corticosteroids was to be assessed.	up to 180 days
Secondary	Phase 2: Cumulative Corticosteroid Dose	The number of participants with various cumulative corticosteroid doses was assessed.	up to 180 days
Secondary	Phase 2: Number of Participants Who Discontinued Corticosteroids	The number of participants who discontinued corticosteroids was assessed.	up to 100 days
Secondary	Phase 2: Number of Participants Who Discontinued Immunosuppressive Medication	The number of participants who discontinued immunosuppressive medication was assessed.	up to 100 days
Secondary	Phase 2: Number of Participants With aGVHD Flares	The number of participants who experienced aGVHD flares requiring treatment was assessed.	up to 100 Days
Secondary	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