The Safety and Tolerability of Pirfenidone for BOS After HCT

Exclusion Criteria

• •1. Any condition that, in the opinion of the investigator, might be significantly exacerbated by the known side effects associated with the administration of pirfenidone e.g., presence of active GVHD of the gastrointestinal tract as manifested by rising liver function tests (LFTs) prior to initiation of study treatment
• •2. Uncontrolled infection
• •3. Major surgery within the past 2 months
• •4. The use of another investigational drug within the previous 30 days.
• •5. Inability to attend scheduled clinic visits
• •6. Inability to perform pulmonary function testing
• •7. Significant clinical change in health in the past 30 days
• •8. Body mass index (BMI) \< 17.5
• •9. Life expectancy \< 6 months due to any condition other than BOS that, in the opinion of the investigator, is likely to result in the death of the patient.
• •10. History of unstable or deteriorating cardiac or pulmonary disease (other than BOS) within the previous 6 months, including but not limited to the following:
• •1. Unstable angina pectoris or myocardial infarction
• •2. Congestive heart failure requiring hospitalization
• •3. Uncontrolled clinically significant arrhythmias
• •11. Pregnancy or lactation.
• •12. Family or personal history of long QT syndrome
• •13. Investigational therapy, defined as any drug that has not been approved for marketing for any indication in cGVHD will be restricted from the study
• •14. The following medications may significantly increase the level of Pirfenidone and should not be taken concurrently including: fluvoxamine, ciprofloxacin \> 500mg twice daily, systemically administered aminolevulinic acid, vemurafenib and enoxacin. Any other strong inhibitors of P450 isoenzymes CYP1A2, CYP2C9, 2C19, 2D6, and 2E1 should be avoided. Participants that cannot take alternative medications to those listed above will be excluded from this study.
• •Laboratory Exclusions
• •1. Any of the following LFT criteria above specified limits: total bilirubin above the upper limit of normal (ULN), excluding patients with Gilbert's syndrome; aspartate or alanine aminotransferase (AST/SGOT or ALT/SGPT) \>3 × ULN; alkaline phosphatase \>2.5 × ULN
• •2. Creatinine clearance (CrCl) \<30 mL/min, calculated using the Cockcroft-Gault formula
• •3. Electrocardiogram (ECG) with a QTc interval \>500 msec at Screening
• •Medication Exclusions
• •1\. Prior use of pirfenidone or known hypersensitivity to any of the components of study treatment.