Itacitinib for Low Risk GVHD
Condition: Low Risk Acute Graft-versus-host Disease; Graft-versus-host-disease; GVHD
MeSH terms: Graft vs Host Disease
Intervention: Itacitinib
Intervention description: for up to 56 days
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: Open label, single arm, non-inferiority study
Masking: None (Open Label)
Enrollment: 70.0
Sex: All
Minimum age: 12 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Graft-versus-host disease; Itacitinib

Summary:

      Graft-versus-host disease (GVHD) is treated with high doses of systemic steroids which can
      lead to serious complications. A new blood test can identify patients whose GVHD is most
      likely to respond to well to treatment (low risk GVHD). This study will test whether patients
      with low risk GVHD can be successfully treated without steroids. Patients who participate
      with this study will be treated with itacitinib instead of steroids. Itacitinib is an
      experimental drug with an excellent safety record and appears to have activity as a GVHD
      treatment.
    

Eligibility criteria:

        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 - 75 years (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 <5x 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