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

Sponsor

Incyte Corporation (Industry)

Overall Status

Terminated

CT.gov ID

NCT03721965

Collaborator

(none)

Enrollment

Locations

Arm

1.6

Actual Duration (Months)

0.1

Patients Per Site

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Graft-versus-host Disease	Drug: Itacitinib Drug: Corticosteroids	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

2 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Dec 31, 2019

Actual Primary Completion Date :

Feb 17, 2020

Actual Study Completion Date :

Feb 17, 2020

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Phase 1: Number of treatment-emergent adverse events (TEAEs) [Up to approximately 12 months]
Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment.
Phase 1: Cmax of itacitinib when administered with corticosteroids [Up to 28 days]
Maximum observed plasma concentration.
Phase 1: Cmin of itacitinib when administered with corticosteroids [Up to 28 days]
Minimum observed plasma concentration.
Phase 1: Tmax of itacitinib when administered with corticosteroids [Up to 28 days]
Time to maximum concentration.
Phase 1: AUC of itacitinib when administered with corticosteroids [Up to 28 days]
Area under the plasma concentration-time curve.
Phase 1: Cl/F of itacitinib when administered with corticosteroids [Up to 28 days]
Apparent oral dose clearance.
Phase 2: Overall response rate [Day 28]
Defined as the proportion of participants demonstrating a complete response (CR), very good partial response (VGPR), or partial response (PR).

Secondary Outcome Measures

Phase 1: Overall response rate [Day 28]
Defined as the proportion of participants demonstrating a complete response (CR), very good partial response (VGPR), or partial response (PR).
Phase 2: Cmax of itacitinib when administered with corticosteroids [Day 7]
Maximum observed plasma concentration.
Phase 2: Cmin of itacitinib when administered with corticosteroids [Day 7]
Minimum observed plasma concentration.
Phase 2: Tmax of itacitinib when administered with corticosteroids [Day 7]
Time to maximum concentration.
Phase 2: AUC of itacitinib when administered with corticosteroids [Day 7]
Area under the plasma concentration-time curve.
Phase 2: Cl/F of itacitinib when administered with corticosteroids [Day 7]
Apparent oral dose clearance.
Phase 2: Overall response rate [Up to 100 days]
Defined as the proportion of participants demonstrating a CR, VGPR, or PR.
Phase 2: Nonrelapse mortality [Up to 24 months]
Defined as the proportion of participants who died due to causes other than underlying hematologic disorders relapse.
Phase 2: Duration of response [Up to approximately 12 months]
Defined as the time of the onset of response to loss of response.
Phase 2: Time to response [Up to approximately 12 months]
Defined as the interval from treatment initiation to first response.
Phase 2: Relapse rate of malignant and nonmalignant disorders [Up to approximately 12 months]
Defined as the proportion of participants whose underlying disease relapses.
Phase 2: Malignant and nonmalignant disorders relapse-related mortality rate [Up to approximately 12 months]
Defined as the proportion of participants whose underlying hematologic disorder relapses and has a fatal outcome.
Phase 2: Failure-free survival [Up to 6 months]
Defined as the proportion of participants who are still alive, have not relapsed, have not required additional therapy for aGVHD, and have not demonstrated signs or symptoms of chronic GVHD.
Phase 2: Overall survival [Up to approximately 12 months]
Defined as the interval from study enrollment to death due to any cause.
Phase 2: Number of adverse events [Up to approximately 12 months]
Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment.
Phase 2: Incidence rate of secondary graft failure [Up to approximately 12 months]
To assess the proportion of participants experiencing secondary graft failure.
Phase 2: Average corticosteroid use [Up to 180 days]
Defined as average number of subjects who discontinue corticosteroids.
Phase 2: Cumulative corticosteroid dose [Up to 180 days]
Defined as proportion of subjects who discontinue corticosteroids
Phase 2: Proportion of participants who discontinue corticosteroids [Up to 100 days]
Defined as proportion of participants who discontinue corticosteroids.
Phase 2: Proportion of participants who discontinue immunosuppressive medication [Up to 100 days]
Defined as proportion of participants who discontinue immunosuppressive medication.
Phase 2: Incidence rate of aGVHD flares [Day 100]
Defined as the incidence of graft-versus-host disease (GVHD) flares.
Phase 1 and 2: Incidence rate of cGVHD [Up to 365 days]
Defined as the incidence of cGvHD

Eligibility Criteria

Criteria

Ages Eligible for Study:

28 Days to 18 Years

Sexes Eligible for Study:

All

Accepts 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.

Contacts and Locations

Locations

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