Graft-versus-host Disease (GVHD)
Conditions
Keywords
Acute Graft Versus Host Disease
Brief summary
To determine if Itacitinib in combination with corticosteroids is safe and tolerable in patients with Grade IIB-IVD acute graft-versus-host disease (GVHD).
Interventions
DRUGItacitinib (200 mg)
DRUGItacitinib (300 mg)
DRUGprednisone or methylprednisolone (corticosteroids)
All subjects will receive prednisone 2.5 mg/kg per day PO (or methylprednisolone 2 mg/kg IV daily) on Days 1 through 5. Subjects will be tapered as tolerated beginning on Day 6 to no less than 0.25 mg/kg per day PO (or methylprednisolone 0.2 mg/kg per day) by Day 28. After Day 28, corticosteroids should be tapered according to institutional guidelines to attain ≤ prednisone 0.2 mg/kg per day (or ≤ methylprednisolone 0.16 mg/kg per day) by Day 56.
Sponsors
Incyte Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have undergone first allo-HSCT from any donor source (matched unrelated donor, sibling, haploidentical) using bone marrow, peripheral blood stem cells, or cord blood for hematologic malignancies. Recipients of nonmyeloablative and myeloablative transplants are eligible. * Clinically suspected Grades IIB to IVD acute GVHD as per modified MN-CIBMTR criteria, occurring after allo-HSCT with any conditioning regimen and any anti-GVHD prophylactic program. * Subjects may, but are not required to, have previously received corticosteroids for acute GVHD: * Evidence of myeloid engraftment. Use of growth factor supplementation is allowed.
Exclusion criteria
* Has received more than 1 hematopoietic stem cell transplantation. * Has progressed on more than 2 prior treatment regimens for acute GVHD. * Presence of an active uncontrolled infection. * Subjects with relapsed primary disease, or subjects who have been treated for relapse after the allogeneic hematopoietic stem-cell transplantation (allo-HSCT) was performed. * Inadequate recovery from toxicity and/or complications from the prior allo-HSCT. * Any corticosteroid therapy (for indications other than GVHD) at doses \> 1 mg/kg per day methylprednisolone or equivalent within 7 days of randomization. * Previously received JAK inhibitor therapy for any indication.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Assess safety and tolerability of study treatment as measured by the frequency and severity of adverse events and serious adverse events | First dose of study drug to 30 days after the last dose of study drug |
Secondary
| Measure | Time frame |
|---|---|
| Overall Response Rate (ORR) | Days 14, 28, 56 and 100 |
| Maximum Observed Plasma Concentration (Cmax) of the two treatment groups Itacitinib | Day 1 and Day 7 |
| Time to Reach the Maximum Plasma Concentration (Tmax) of the two treatment groups Itacitinib | Day 1 and Day 7 |
| Area Under the Plasma Concentration-time Curve (AUC) of the two treatment groups Itacitinib | Day 1 and Day 7 |
| Minimum observed plasma concentration (Cmin) of the two treatment groups Itacitinib | Day 1 and Day 7 |
Countries
United States
Outcome results
None listed