Study of Itacitinib in Combination With Corticosteroids for the Treatment of Acute GVHD

Study Overview
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Brief Summary
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To determine if Itacitinib in combination with corticosteroids is safe and tolerable in patients with Grade IIB-IVD acute graft-versus-host disease (GVHD).

Official Title
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A Randomized, Parallel-Cohort Phase 1 Study of Itacitinib in Combination With Corticosteroids for the Treatment of Acute Graft Versus Host Disease

Conditions
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Graft-versus-host Disease (GVHD)

Intervention / Treatment
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* Drug: Itacitinib (200 mg)
* Drug: Itacitinib (300 mg)
* Drug: prednisone or methylprednisolone (corticosteroids)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Itacitinib (200 mg)<br>Itacitinib (200 mg) + prednisone or methylprednisolone (corticosteroids) | Drug: Itacitinib (200 mg)<br> <br> * Other names: INCB039110;Drug: prednisone or methylprednisolone (corticosteroids)<br>* 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.<br>|
| Experimental: Itacitinib (300 mg)<br>Itacitinib (300 mg) + prednisone or methylprednisolone (corticosteroids) | Drug: Itacitinib (300 mg)<br> <br> * Other names: INCB039110;Drug: prednisone or methylprednisolone (corticosteroids)<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Graft Versus Host Disease