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

Phase 2TerminatedNCT03721965

Incyte Corporation2 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Acute Graft-versus-host Disease

Interventions

ItacitinibDRUG

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.

CorticosteroidsDRUG

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.

Eligibility

Sex: ALLMin age: 28 DaysMax age: 18 Years

Medical Language ↔ Plain English

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.

Locations (38)

Outcomes

Primary Outcomes

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.

Time frame: up to 45 days

Phase 1: Cmax of Itacitinib When Administered With Corticosteroids

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

Phase 1: Cmin of Itacitinib When Administered With Corticosteroids

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

Phase 1: Tmax of Itacitinib When Administered With Corticosteroids

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

Phase 1: AUC of Itacitinib When Administered With Corticosteroids

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

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

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

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).

Data from ClinicalTrials.gov

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City of Hope National Medical Center

Duarte, California, United States

Childrens Hospital of Orange County

Orange, California, United States

Children's Hospital Colorado - Center for Cancer and Blood Disorders

Aurora, Colorado, United States

Nemours/A.I. duPont Hospital for Children

Wilmington, Delaware, United States

Nicklaus Children's Hospital

Miami, Florida, United States

University of Minnesota Medical Center

Minneapolis, Minnesota, United States

Memorial Sloan Kettering Cancer Center

New York, New York, 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

Doernbecher Children's Hospital - Division of Pediatric Hematology

Portland, Oregon, United States

...and 28 more locations

Secondary Outcomes

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.

Time frame: up to 12 months

Phase 2: Cmax of Itacitinib When Administered With Corticosteroids

Cmax was defined as the maximum observed plasma concentration.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.