Male or female, 18 years of age or older 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 Classification code
Conditions
Sponsors
Incyte Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Male or female, 18 years of age or older. • Has undergone 1 allo-HSCT from any donor (related or unrelated with any degree of HLA matching) and any donor source (bone marrow, peripheral blood stem cells, or cord blood) for a hematologic malignancy or disorder. Recipients of myeloablative and reduced-intensity conditioning regimens are eligible. • Clinically suspected Grade II to IV aGVHD as per MAGIC criteria, occurring after allo-HSCT and any GVHD prophylaxis regimen. Biopsies should be obtained to pathologically confirm aGVHD; in cases where a biopsy is negative, is unable to be obtained, or is clinically contraindicated, clinical suspicion of aGVHD by the treating physician is sufficient, provided that alternative diagnoses of drug effects or infection are adequately ruled out. • Evidence of myeloid engraftment (eg, absolute neutrophil count = 0.5 × 109/L for 3 consecutive assessments if ablative therapy was previously used). Use of growth factor supplementation is allowed. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 393 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 43
Exclusion criteria
Exclusion criteria: • Has received more than 1 allo-HSCT. • Has received more than 2 days of systemic corticosteroids for acute-GVHD. • Presence of GVHD overlap syndrome. • Presence of an active uncontrolled infection.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Compare the efficacy of itacitinib in combination with corticosteroids versus placebo in combination with corticosteroids in terms of overall response rate (ORR) at Day 28 in subjects with acute graft-versus-host disease (aGVHD).; Secondary Objective: - Compare the efficacy between treatment cohorts at a subsequent key clinical landmark (key secondary objective). - Compare additional response and longer-term efficacy outcomes between treatment cohorts. - Assess the incidence and severity of adverse events (AEs) and serious adverse events. - Evaluate the pharmacokinetics of itacitinib when administered in combination with corticosteroids. - Evaluate the incidence of secondary graft failure. - Evaluate the use and discontinuation of corticosteroids. - Evaluate the use and discontinuation of immunosuppressive medications. - Evaluate the incidence of aGVHD flares. - Evaluate the incidence of cGVHD. ;Primary end point(s): ORR at Day 28, defined as the proportion of subjects demonstrating a complete response (CR), very good partial response (VGPR), or partial response (PR).;Timepoint(s) of evaluation of this end point: Day 28 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - NRM at Month 6, defined as the proportion of subjects who died due to causes other than malignancy relapse at Month 6 (key secondary endpoint). - ORR, defined as the proportion of subjects demonstrating a CR, VGPR, or PR at Days 14, 56, and 100. - NRM at Months 9, 12, and 24. - 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. - Malignancy relapse rate, defined as the proportion of subjects whose underlying malignancy relapses. - Malignancy relapse-related mortality rate, defined as the proportion of subjects whose malignancy 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 (OS), defined as the interval from study enrollment to death due to any cause. - Clinical safety data (eg, AEs, infections) will be tabulated and listed. - Cmax, Cmin, tmax, AUC, and CL/F. - Incidence rate of secondary graft failure, defined as > 95% recipient cells any time after engraftment with no signs of relapse, OR retransplantation because of secondary neutropenia (< 0.5 × 109/L) and/or thrombocytopenia (< 20 × 109/L) within 2 months of transplant. - Average and cumulative corticosteroid dose at Days 28, 56, 100, and 180; proportion of subjects who discontinue corticosteroids at Days 56 and 100. - Proportion of subjects who discontinue immunosuppressive medic | — |
Countries
Australia, Austria, Belgium, Canada, Czech Republic, Finland, Greece, Hungary, Israel, Korea, Republic of, Netherlands, New Zealand, Portugal, Singapore, Spain, Switzerland, Taiwan, Turkey, United Kingdom, United States
Contacts
Public ContactClinical Trial Information
Incyte Corporation
Outcome results
None listed