Safety and Efficacy of Itacitinib in Combination With Corticosteroids for Treatment of Graft-Versus-Host Disease in Pediatric Subjects
- Conditions
- Acute Graft-versus-host Disease
- Interventions
- Drug: Corticosteroids
- Registration Number
- NCT03721965
- Lead Sponsor
- Incyte Corporation
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 2
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Itacitinib + Corticosteroids Itacitinib - Itacitinib + Corticosteroids Corticosteroids -
- Primary Outcome Measures
Name Time Method Phase 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs) up to 45 days 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 Day 1: 1, 2, 4, and 6 hours post-dose. Day 7: predose; 1, 2, 4, and 6 hours post-dose Cmax was defined as the maximum observed plasma concentration.
Phase 1: Cmin of Itacitinib When Administered With Corticosteroids Day 1: 1, 2, 4, and 6 hours post-dose. Day 7: predose; 1, 2, 4, and 6 hours post-dose Cmin was defined as the minimum observed plasma concentration.
Phase 1: Tmax of Itacitinib When Administered With Corticosteroids Day 1: 1, 2, 4, and 6 hours post-dose. Day 7: predose; 1, 2, 4, and 6 hours post-dose Tmax was defined as the time to the maximum concentration.
Phase 1: AUC of Itacitinib When Administered With Corticosteroids Day 1: 1, 2, 4, and 6 hours post-dose. Day 7: predose; 1, 2, 4, and 6 hours post-dose AUC was defined as the area under the plasma concentration-time curve.
Phase 1: Cl/F of Itacitinib When Administered With Corticosteroids Day 1: 1, 2, 4, and 6 hours post-dose. Day 7: predose; 1, 2, 4, and 6 hours post-dose Cl/F was defined as the apparent oral dose clearance.
Phase 2: Overall Response Rate up to Day 28 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
Name Time Method Phase 2: Relapse Rate of Malignant and Nonmalignant Disorders up to approximately 12 months Relapse rate was defined as the number of participants whose underlying disease relapsed.
Phase 2: Malignant and Nonmalignant Disorders Relapse-related Mortality Rate up to approximately 12 months Mortality rate was defined as the number of participants whose underlying hematologic disorder relapsed and had a fatal outcome.
Phase 2: Failure-free Survival up to 6 months 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 up to approximately 12 months Overall survival was defined as the interval from study enrollment to death due to any cause.
Phase 2: Incidence Rate of Secondary Graft Failure up to approximately 12 months Analysis was to be conducted to assess the number of participants experiencing secondary graft failure.
Phase 2: Average Corticosteroid Use up to 180 days The average number of participants who discontinued corticosteroids was to be assessed.
Phase 2: Number of Participants With TEAEs up to 12 months 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 Day 7: predose; 1, 2, and 4 hours post-dose Cmax was defined as the maximum observed plasma concentration.
Phase 2: Cmin of Itacitinib When Administered With Corticosteroids Day 7: predose; 1, 2, and 4 hours post-dose Cmin was defined as the minimum observed plasma concentration.
Phase 2: Tmax of Itacitinib When Administered With Corticosteroids Day 7: predose; 1, 2, and 4 hours post-dose Tmax was defined as the time to the maximum concentration.
Phase 2: AUC of Itacitinib When Administered With Corticosteroids Day 7: predose; 1, 2, and 4 hours post-dose AUC was defined as the area under the plasma concentration-time curve.
Phase 2: Cl/F of Itacitinib When Administered With Corticosteroids Day 7: predose; 1, 2, and 4 hours post-dose Cl/F was defined as the apparent oral dose clearance.
Phase 2: Overall Response Rate up to 100 Days 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 up to Day 28 Overall response rate was defined as the number of participants demonstrating a CR, a VGPR, or a PR.
Phase 2: Non Relapse Mortality up to 24 months 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 up to approximately 12 months Duration of response was defined as the time of the onset of response to the loss of response.
Phase 2: Time to Response up to approximately 12 months Time to response was defined as the interval from treatment initiation to the first response.
Phase 2: Cumulative Corticosteroid Dose up to 180 days The number of participants with various cumulative corticosteroid doses was assessed.
Phase 2: Number of Participants Who Discontinued Corticosteroids up to 100 days The number of participants who discontinued corticosteroids was assessed.
Phase 2: Number of Participants Who Discontinued Immunosuppressive Medication up to 100 days The number of participants who discontinued immunosuppressive medication was assessed.
Phase 2: Number of Participants With aGVHD Flares up to 100 Days The number of participants who experienced aGVHD flares requiring treatment was assessed.
Phase 2: Number of Participants With Chronic Graft-versus-host Disease (cGVHD) up to 365 days The number of participants with a diagnosis of any cGVHD, including mild, moderate, severe, was assessed.
Trial Locations
- Locations (36)
University of Minnesota Medical Center
🇺🇸Minneapolis, Minnesota, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
University Hospitals Cleveland Medical Center - Rainbow Babies and Children's Hospital
🇺🇸Cleveland, Ohio, United States
Children's Hospital of Philadelphia - Center for Childhood Cancer Research
🇺🇸Philadelphia, Pennsylvania, United States
Childrens Hospital of Orange County
🇺🇸Orange, California, United States
Robert Debre Hospital
🇫🇷Paris, France
Royal Marsden Hospital - Surrey
🇬🇧Surrey Quays, United Kingdom
City of Hope National Medical Center
🇺🇸Duarte, California, United States
CHU Nancy
🇫🇷Vandœuvre-lès-Nancy, France
Universitatsklinikum Jena, Klinik fur Kinder und Jugendmedizin
🇩🇪Jena, Germany
Doernbecher Children's Hospital - Division of Pediatric Hematology
🇺🇸Portland, Oregon, United States
Sarah Cannon Research Institute, LLC
🇺🇸Nashville, Tennessee, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Children's Hospital Colorado - Center for Cancer and Blood Disorders
🇺🇸Aurora, Colorado, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Nicklaus Children's Hospital
🇺🇸Miami, Florida, United States
Universitaetsklinikum Aachen, AoeR
🇩🇪Aachen, Germany
Fred Hutchinson Cancer Research Center
🇺🇸Seattle, Washington, United States
Centre Hospitalier Universitaire de Rennes
🇫🇷Rennes, Cedex 2, France
CHU de Grenoble
🇫🇷Grenoble, France
CHRU Nancy
🇫🇷Vandœuvre-lès-Nancy, France
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, Italy
Hospital Vall D Hebron
🇪🇸Barcelona, Spain
Hospital Clinico de Santiago de Compostela
🇪🇸Santiago De Compostela, Spain
Hospital Universitari i Politecnic La Fe
🇪🇸Valencia, Spain
Great Ormond Street Hospital for Children
🇬🇧London, United Kingdom
Bristol Royal Hospital for Children
🇬🇧Bristol, United Kingdom
Birmingham Childrens Hospital
🇬🇧Birmingham, United Kingdom
Leeds Teaching Hospitals NHS Trust
🇬🇧Leeds, United Kingdom
Central Manchester University Hospital - Royal Manchester Children's Hospital
🇬🇧Manchester, United Kingdom
Hopitaux Universitaires De Strasbourg
🇫🇷Strasbourg Cedex, France
Nemours/A.I. duPont Hospital for Children
🇺🇸Wilmington, Delaware, United States