Male or female, 28 days to less than 18 years of age, who have received an allogeneic hematopoietic stem cell transplant (allo-HSCT) and have developed Grade II to IV acute GVHD MedDRA version: 20.1 Level: PT Classification code 10066260 Term: Acute graft versus host disease System Organ Class: 10021428 - Immune system disorders MedDRA version: 20.1 Level: PT Classif
Conditions
Sponsors
Incyte Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Male and female subjects from 28 days to 12 years old) greater than 50 mL/min (using the Cockcroft-Gault formula and actual body weight); for pediatric subjects (= 1 to 12 years old), glomerular filtration rate (GFR) > 70 mL/min/1.73 m2 as estimated using local institutional methods (eg, modified Schwartz formula or other validated methods). Are the trial subjects under 18? yes Number of subjects for this age range: 150 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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, defined as hemodynamic instability attributable to sepsis or new symptoms, worsening physical signs, or radiographic findings attributable to infection. Persisting fever without signs or symptoms will not be interpreted as an active uncontrolled infection.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase 1: - To assess the safety and tolerability of itacitinib in combination with corticosteroids in pediatric subjects with Grade II-IV steroid-naive (SN) acute graft-versus-host disease (aGVHD). - To evaluate the pharmacokinetics (PK) of itacitinib when administered in combination with corticosteroids. Phase 2: - To assess the efficacy of itacitinib in combination with corticosteroids in terms of overall response rate (ORR) at Day 28 in pediatric subjects with aGVHD. ; Secondary Objective: Phase 1: - To assess the efficacy of itacitinib in combination with corticosteroids in terms of ORR at Day 28 in pediatric subjects with aGVHD. Phase 2: - To evaluate the PK of itacitinib when administered in combination with corticosteroids. Phase 1 and 2: - To evaluate additional efficacy and longer-term efficacy outcomes. - To assess the incidence and severity of AEs and SAEs. - To evaluate the incidence of secondary graft failure. - To evaluate the use and discontinuation of corticosteroids. - To evaluate the use and discontinuation of immunosuppressive medications. - To evaluate the incidence of aGVHD flares. - To evaluate the incidence of cGVHD. ; Primary end point(s): Phase 1: • Frequency, duration, and severity of adverse events (AEs) and serious adverse events (SAEs) • Changes in vital signs and clinical evaluations. • Changes in clinical laboratory blood samples. • Cmax, Cmin, Tmax, AUC, and Cl/F assessed at Day 1, 7, and 28. Phase 2: • ORR at Day 28, defined as the proportion of subjects demonstrating a complete response (CR), very good partial response (VGPR), or | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Day1 , 7, 14, 21, 28, 35, 42, 49, 56, 100, 180, 365 Months 9 and 24. ; Secondary end point(s): Phase 1: • ORR at Day 28, defined as the proportion of subjects demonstrating a CR, VGPR, or PR. Phase 2: • Cmax, Cmin, Tmax, AUC, and Cl/F assessed at Day 7. Phase 1 & 2: • ORR, defined as the proportion of subjects demonstrating a CR, VGPR, or PR, at Days 14, 56, and 100. • Nonrelapse mortality (NRM), defined as the proportion of subjects who died due to causes other than underlying hematological disorders at Months 6, 9, 12, and 24. • Duration of response (DOR) for responders will be calculated. The DOR is defined from the time of the onset of response to loss of response. Subjects who died or discontinued will be censored at the death date or the previous assessment. • Time to response, defined as the interval from treatment initiation to first response. • Relapse rate of malignant and non-malignant disorders, defined as the proportion of subjects whose underlying disease relapses. • Malignant and non-malignant disorders relapse–related mortality rate, defined as the proportion of subjects whose underlying disease relapses and has a fatal outcome. • Failure-free survival, defined as the proportion of subjects who are still alive, have not relapsed, have not required additional therapy for aGVHD, and have not demonstrated signs or symptoms of chronic graft-versus-host disease (cGVHD), at Month 6. • Overall survival, defined as the interval from study enrollment to death due to any cause. • Clinical safety data (eg, AEs, infections) will be tabulated and listed. • Incidence rate of secondary graft failure, defined as > 95% recipient cells any ti | — |
Countries
Belgium, France, Germany, Italy, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trial Information
Incyte Corporation
Outcome results
None listed