Study of Ruxolitinib in Sclerotic Chronic Graft-Versus-Host Disease After Failure of Systemic Glucocorticoids

Inclusion Criteria: 1. Sclerotic chronic GVHD (classic chronic or overlap syndrome) that meets 2014 NIH Consensus Criteria. Eligible patients will have superficial or deep skin sclerosis, fasciitis or joint contractures. 2. The subject must have received the following therapy for chronic GVHD (not necessarily for sclerotic manifestations): A - Systemic corticosteroids for \>12 months and at least one additional line of systemic therapy OR B - Systemic corticosteroids and at least two additional lines of systemic therapy. For the purpose of this study, fluticasone, azithromycin and montelukast ("FAM") therapy for lung GVHD will be considered a topical therapy. Investigators are encouraged but not mandated to use ibrutinib for appropriate patients prior to enrollment in this trial. 3. Adults, Age ≥18 years (state of Nebraska, Age ≥19 years) 4. Karnofsky performance status ≥60% at the time of enrollment 5. All allogeneic donor sources and all conditioning regimens are allowed. 6. Absolute neutrophil count (ANC) greater than 1000/µL, and platelet count ³50,000/µL without the use of growth factors or platelet transfusion. 7. Able to take orally-administered medication. 8. Female patient of reproductive potential must have a negative serum or urine pregnancy test ≤7 days prior to starting the study drug. Women are considered NOT to have reproductive potential if they have had 12 months of amenorrhea with an appropriate clinical profile (i.e. ≥51 years, history of vasomotor symptoms, OR supportive hormone levels such as low estrogen and high follicle-stimulating hormone levels), OR surgical sterilization. 9. Male and female patients of reproductive potential must be willing to avoid pregnancy or fathering children from enrollment to one month after the end of study treatment. This will require either a total abstinence, OR exclusively non-heterosexual activity (when this is in line with the preferred and usual lifestyle of the subject), OR two methods of contraception (male or female condom with or without a spermicidal agent, diaphragm or cervical cap with spermicide, or hormonal based contraception including intrauterine device). 10. Life expectancy greater than 6 months 11. Written informed consent to participate in the study. Exclusion Criteria: 1. Fibrosis of internal organs such as gut, liver or lung as the sole manifestation of sclerosis. 2. Fluconazole at a dose more than 200 mg daily. Patients should stop fluconazole or lower dose to less than or equal to 200 mg daily before starting ruxolitinib. 3. Current evidence of malignancy after allogeneic transplant. 4. History of progressive multifocal leuko-encephalopathy (PML) 5. Active uncontrolled bacterial, fungal, parasitic, or viral infection. Infections are considered controlled if appropriate therapy has been instituted and, at the time of screening, no signs of infection progression are present. Progression of infection is defined as hemodynamic instability attributable to sepsis, new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection 6. Presence of known HIV infection, active hepatitis B or C infection. 7. Active tuberculosis infection that developed after allogeneic hematopoietic cell transplant (HCT) 8. Total bilirubin 1.5 ´ the upper limit of the normal range 9. Creatinine clearance \<30 mL/min 10. 10\. Presence of uncontrolled cardiopulmonary conditions such as ongoing cardiac arrhythmias, unstable angina or myocardial infarction, uncontrolled hypertension (e.g. blood pressure higher than 150/90 for patients 60 years or older, or higher than 140/90 for patients younger than 60 years, or those with diabetes and chronic kidney disease), New York Heart Association class III/IV congestive heart failure, or requirement of supplemental oxygen at rest or having a resting O2 saturation \<90% by pulse oximetry. 11. Any other condition that is judged by the physician to potentially interfere with compliance to the study protocol or pose a significant risk to the patient. 12. Pregnancy, breastfeeding or planning to be pregnant. 13. Exposure to Janus kinase inhibitors (JAK) inhibitor therapy for any indication after allogeneic transplant 14. Initiation of a new systemic immunosuppressant for management of chronic GVHD within 8 weeks prior to enrollment. However, patients who develop disease progression can enroll as early as 4 weeks after initiation of a new systemic immunosuppressant. Also, patients who are unable to tolerate current therapy can enroll any time after initiation of a new systemic immunosuppressant, as long as the "new" immunosuppressant is stopped in these cases prior to initiation of ruxolitinib. Initiation of any new topical therapy (including FAM or intra-oral narrow-band UVB phototherapy) and changes in dose of existing immunosuppressive agents such as corticosteroids, sirolimus, calcineurin inhibitors or other agents are acceptable at any time prior to enrollment. The use of immunosuppressants for short term period, for example 7 days, for indications other than GVHD will be acceptable. 15. Treatment with any other investigational agent, device, or procedure, within 21 days (or 5 half-lives, whichever is greater) 16. Known allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds.