Itacitinib for the Treatment of Bronchiolitis Obliterans Syndrome after Donor Hematopoietic Cell Transplant

Inclusion Criteria

• BOS diagnosed within the past 6 months of enrollment, defined by 2015 National Institutes of Health (NIH) Consensus Criteria
• Age 18-75 years
• Undergone allogeneic stem cell transplant (SCT)
• Absolute neutrophil count (ANC) > 1,000/uL
• Hemoglobin > 8 gm/dL (untransfused)
• Platelet count > 25,000/uL (untransfused)
• Karnofsky performance score >= 60
• The ability to understand and sign a written informed consent form
• Contraception for women and men of child bearing potential. Permitted methods should be at least 99% effective in preventing pregnancy
• Male patients must be willing to refrain from donating sperm during their participation in the study and for at least 3 months after completing the study

Exclusion Criteria

• Prior treatment with any other JAK inhibitor (including ruxolitinib) for BOS or any other indication within the past 6 months of enrollment
• Patients on mechanical ventilation or resting by pulse oximetry oxygen (O2) saturation < 88%
• Forced expiratory volume in 1 second (FEV1) < 40% predicted
• Relapsed primary malignancy for which SCT was performed
• History of progressive multifocal leuko-encephalopathy (PML)
• Active uncontrolled bacterial, fungal, parasitic, or viral infection
• Known human immunodeficiency virus (HIV) infection or active hepatitis B or C infections
• History of tuberculosis anytime after SCT
• Severe renal dysfunction defined by serum creatinine > 2 mg/dL, creatinine clearance < 60 mL/minute or dialysis dependence
• Serum transaminases > 5 x upper limit of normal
• Inability to perform pulmonary function test (PFT) reliably
• Positive beta human chorionic gonadotropin (HCG) test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization
• Lactating/nursing women
• Life expectancy < 6 months
• Other severe organ dysfunction unrelated to underlying graft-versus host disease (GVHD). For example, uncontrolled or significant cardiac disease, including any of the following: recent myocardial infarction (within last 6 months from randomization); New York Heart Association Class III or IV congestive heart failure; unstable angina (within last 6 months prior to randomization); clinically significant (symptomatic) cardiac arrhythmias (e.g., sustained ventricular; tachycardia, and clinically significant second or third degree atrioventricular (AV) block without a pacemaker); uncontrolled hypertension. Or any other concurrent severe and/or uncontrolled medical conditions which, in the opinion of the investigator, could compromise participation in the study, pose a significant risk to the subject, or interfere with study results