Novel BET Inhibitor PLX51107 for Steroid-Refractory Acute GVHD

Exclusion Criteria

• •Prior exposure to a bromodomain inhibitor
• •Evidence of chronic GVHD
• •Evidence of active relapse of disease
• •Exposure to other investigational or anti-cancer therapies (not for GVHD) within 28 days or 5 half-lives (whichever is shorter) of first administration of study drug
• •Active, uncontrolled bacterial, fungal, or viral infection
• •Known or suspected allergy to the study drug
• •Clinically significant cardiac disease, defined as:
• •* Clinically significant cardiac arrhythmias, including bradyarrhythmia, and/or a need for anti-arrhythmic therapy (excluding beta blockers or digoxin). Individuals with controlled atrial fibrillation are not excluded
• •* Fridericia-corrected QT interval (QTcF) \>= 450 ms (male) or \>= 470 ms (female) at screening
• •* History of clinically significant cardiac disease or congestive heart failure greater than New York Heart Association Class II. Subjects must not have unstable angina (angina symptoms at rest) or experienced either new-onset angina within the last 3 months or myocardial infarction (MI) within the last 6 months unless it was due to the underlying disease and there has been appropriate revascularization. Individuals with ambiguous troponin levels that are not diagnostic of an MI should be discussed with the principal investigator (PI) prior to enrollment
• •* Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism within the 6 months before start of study medication (except for catheter-related venous thrombosis
• •Inability to take oral medication or significant nausea and vomiting, malabsorption, or significant small bowel resection that, in the opinion of the Investigator, would preclude adequate absorption
• •Active thrombotic microangiopathy (TMA)
• •Women who are either pregnant or breast feeding
• •Measured or calculated (Cockcroft-Gault formula) creatinine clearance (CrCl) \< 45 mL/min
• •Prothrombin time or international normalized ratio \> 1.5 x upper limit of normal (ULN)
• •Activated partial thromboplastin time \> 1.5 x ULN
• •Requiring mechanical ventilation or vasopressor support
• •Subject is participating in any other therapeutic clinical study (observational or registry studies are allowed)