Inclusion Criteria: 

• Newly diagnosed GVHD that meets criteria for Minnesota standard risk.
• Ann Arbor 1 GVHD by biomarkers.
• GVHD not previously treated systemically (topical therapies and non-absorbed steroids are allowed).
• Any donor type, HLA-match, conditioning regimen is acceptable.
• Age 12 years and up (children < 18 years must also weigh 50 kg or more).
• Patients must be engrafted post-transplant (ANC > 500/μL and platelet count > 20,000). Use of growth factor supplementation to maintain neutrophil count is allowed. 
• Direct bilirubin must be < 2 mg/dL unless the elevation is known to be due to Gilbert syndrome within 3 days prior to enrollment. 
• ALT/SGPT and AST/SGOT must be < 5 x the upper limit of the normal range within 3 days prior to enrollment. 
• Signed and dated written informed consent obtained from patient or legal representative.

Exclusion Criteria:

• Patients currently being treated with any JAK inhibitor including ruxolitinib. 
• Relapsed, progressing, or persistent malignancy requiring withdrawal of systemic immune suppression.
• Patients with uncontrolled infection (i.e., progressive symptoms related to infection despite treatment or persistently positive microbiological cultures despite treatment or any other evidence of severe sepsis).
• Severe organ dysfunction including requirement for dialysis, mechanical ventilation or oxygen supplementation exceeding 40% FiO2 within 7 days of enrollment. 
• Creatinine clearance or estimated glomerular filtration rate < 30 ml/min as calculated by institutional practice (e.g., Cockcroft-Gault equation, CKD-EPI equation, etc.).
• A clinical presentation resembling de novo chronic GVHD or overlap syndrome developing before or present at the time of enrollment .
• Patients receiving corticosteroids >10 mg/day prednisone (or other steroid equivalent) for any indication within 7 days before the onset of acute GVHD except for adrenal insufficiency or premedication for transfusions/IV meds.
• Patients who are pregnant. 
• Patients receiving investigational agents within 30 days of enrollment. However, the Principal Investigator (PI) may approve prior use of an investigational agent if the agent is not expected to interfere with the safety or the efficacy of itacitinib.
• History of allergic reaction to itacitinib or any JAK inhibitor.