Glasdegib in Refractory Patients With Sclerotic Chronic Graft-Versus-Host Disease

Inclusion Criteria: 1. Adult (≥ 18 years old) recipients of an allogeneic hematopoietic stem cell transplantation with active sclerotic cGVHD without response, in partial response or in relapse after 2 previous lines of treatment including corticosteroids and one of the following second line treatments: * Extracorporeal photopheresis (preferably). * A calcineurin inhibitor. * A mammalian target of rapamycin (mTOR) inhibitor. * Pentostatin. * Rituximab. * Imatinib. * Ruxolitinib. 2. Eastern Cooperative Oncology Group Performance Status 0 to 2. 3. Adequate organ function as defined by the following: * Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) ≤ 3 x upper limit of normal (ULN). * Total serum bilirubin ≤ 2 x ULN (except patients with documented Gilbert's syndrome). * Serum creatinine ≤ 1.5 x ULN or estimated creatinine clearance ≥ 60 mL/min as calculated using the method standard for the institution. 4. Hematologic malignancy in complete remission. 5. Resolved acute effects of any prior therapy to baseline severity or Grade ≤ 1 CTCAE except for adverse events not constituting a safety risk by investigator judgement. 6. Serum/urine pregnancy test (for females of childbearing potential) that is negative at screening and immediately prior to initiation of treatment (first dose). Male and female patients of childbearing potential must agree to use highly effective methods of contraception throughout the study and for at least 180 days after the last dose of assigned treatment. A patient is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children and is sexually active. 7. Evidence of a personally signed and dated informed consent document indicating that the patient (or a legal representative) has been informed of all pertinent aspects of the study. 8. Willingness and ability to comply with the study scheduled visits, treatment plans, laboratory tests and other procedures. Exclusion Criteria: Patients presenting with any of the following will not be included in the study: 1. Patients with active malignancy with the exception of basal cell carcinoma, nonmelanoma skin cancer or cervical carcinoma-in-situ. Other prior or concurrent malignancies will be considered on a case-by-case basis. 2. Any one of the following, currently or in the previous 6 months: myocardial infarction, congenital long QT syndrome, torsade de pointes or clinically significant ventricular arrhythmias. 3. QTc interval \>470 milliseconds using the Fridericia (QTcF). 4. Patients with an active, life threatening or clinically significant uncontrolled systemic infection. 5. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness or active Hepatitis B or C infection. 6. Known malabsorption syndrome or other condition that may impair absorption of study medication (e.g., gastrectomy or lap band). 7. Major surgery or radiation within 4 weeks of starting study treatment. 8. Prior treatment with: * A hedgehog inhibitor at any time. * An investigational agent for the treatment of cGVHD (a three-month wash-out period will be required). 9. Concurrent treatment with any investigational agent. 10. Concurrent administration of herbal preparations. 11. Current use at time of study entry or anticipated need for drugs that are known strong CYP3A4/5 inducers. 12. Current drug or alcohol abuse. 13. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study. 14. Patients who are investigational site staff members or relatives of those site staff members directly involved in the conduct of the trial. 15. Pregnant females; breastfeeding females; males and females of childbearing potential not using two methods of highly effective contraception or not agreeing to continue two methods of highly effective contraception for at least 180 days after last dose of investigational product. 16. Recent or active suicidal ideation or behaviour.