Itacitinib (INCB039110) and Extracorporeal Photopheresis (ECP) for First-Line Treatment in Chronic GVHD

Inclusion Criteria: * -Male or female subject aged ≥ 18 years. * Active, clinically diagnosed, moderate or severe chronic GVHD as defined by the NIH Consensus Development Project Criteria (See Appendix 2). * History of an allogeneic hematopoietic cell transplant with any conditioning regimen, donor, or graft source. * Need for systemic treatment for chronic GVHD as assessed by the treating investigator. * No previous systemic treatment for chronic GVHD. Note: Participants may be receiving immunosuppressants for the prophylaxis or treatment of acute GVHD, but these medications must have been stable for at least 2 weeks prior to the initiation of study therapy. Prednisone dose (or its equivalent) should be at doses of ≤0.25 mg/kg/d for at least 2 weeks prior to the initiation of study therapy. Topical or inhaled treatments for chronic GVHD are allowed. Any prior ECP treatments for the management of acute GVHD must have occurred \> 4 weeks prior to the initiation of itacitinib treatment. * Able to swallow and retain oral medication. * Life expectancy \> 24 weeks. * Karnofsky performance status ≥ 60 * Evidence of myeloid and platelet engraftment: * Absolute neutrophil count ≥ 1000/microliter (mcL) * Platelet count ≥ 25,000/mcL Note: Use of growth factors and transfusion support is allowed during the study; however, growth factors and transfusion support to reach a minimum absolute neutrophil count (ANC) or platelet count for inclusion are not allowed within the 7 days before the screening laboratory assessment. * Adequate organ function as defined as: * Hepatic: * Total bilirubin ≤ 2 mg/dL * alanine transaminase (AST)(SGOT)/aspartate aminotransferase (ALT)(SGPT) ≤ 2.5 × institutional upper limit of normal (ULN) (unless of non-hepatic origin). AST/ALT ≤ 5 x ULN is acceptable if associated with chronic GVHD. * Renal: ---estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2 as calculated using the Modification of Diet in Renal Disease formula or by the Cockcroft-Gault formula: * Males: ((140-age)×weight\[kg\])/(serum creatinine \[mg/dL\]×72) * Females: (((140-age)×weight\[kg\])/(serum creatinine \[mg/dL\]×72))×0.85 * Coagulation: * PT/ international normalized ratio (INR) \< 1.5 x ULN and PTT (aPTT) \< 1.5 x ULN (unless abnormalities are unrelated to coagulopathy or bleeding disorder). When treated with warfarin or other vitamin K antagonist, then INR ≤ 3 x ULN. * Willingness to avoid pregnancy or father children based on the criteria below and as described in Section 5.4.2: * Woman of non-childbearing potential (i.e., surgically sterile with a hysterectomy and/or bilateral oophorectomy for at least 3 months OR ≥ 12 months of amenorrhea and at least 50 years of age). * Woman of childbearing potential who has a negative serum pregnancy test at screening and negative urinary test before the first dose on Day 1 and who agrees to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through safety follow-up. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the subject and their understanding confirmed. * Men who agree to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through safety follow-up. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the subject and their understanding confirmed. * Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines. Exclusion Criteria: * Subjects with score 3 lung GVHD; or biopsy-proven bronchiolitis obliterans. * Participants have uncontrolled manifestations of acute GVHD. * Treatment with any investigational medication within ≤ 30 days or 5 half-lives, whichever is longer, before the first dose of study drug. * Patients who have received any previous systemic treatment for chronic GVHD, including corticosteroids, prior to Cycle 1, Day 1. Note: Prior and concomitant use of Calcineurin-Inhibitors (CNIs) for prevention and treatment of acute GVHD, as well as topical/inhaled steroids, is acceptable. * Received prior Janus kinase (JAK) inhibitor therapy for any indication ≤ 4 weeks prior to Cycle 1 Day 1. * Patients with relapsed or progressive malignant disease or any post-transplant lymphoproliferative disease. * Chronic GVHD occurring after a non-scheduled donor lymphocyte infusion (DLI) administered for pre-emptive treatment of malignancy recurrence. Participants who have received a scheduled DLI as part of their transplant procedure and not for management of malignancy relapse are eligible. * Inability to swallow food or any condition of the upper gastrointestinal tract that precludes the administration of oral medications. * Any contraindication for extracorporeal photopheresis (ECP) per the treating investigator's discretion. * Subject has a concurrent illness which in the opinion of the investigator may interfere with the treatment and evaluation of the subject. * Pregnant or currently breast-feeding. Note: INCB039110 is a Janus kinase 1 (JAK1) inhibitor with the potential for serious or life-threatening birth defects or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with INCB039110, breastfeeding should be discontinued if the mother is treated with INCB039110. These potential risks may also apply to other agents used in this study. * Vaccinated with live, attenuated vaccines within 4 weeks of the first dose of study drug and while on trial. * Use of any prohibited concomitant medications as described in Section 6.5. A washout period of prohibited medications for a period of at least 5 half-lives or as clinically indicated should occur prior to the start of treatment. * Inadequate recovery from toxicity and/or complications from major surgery before starting therapy. * Unwillingness to be transfused with blood components during the study. * History of other malignancy (not including the underlying malignancy that was the indication for the transplant), with the following exceptions: * Malignancy treated with curative intent and with no evidence of active disease present for more than 3 years prior to Screening and felt to be at low risk for recurrence by the treating physician. * Adequately treated non-melanomatous skin cancer or lentigo maligna melanoma without current evidence of disease. * Adequately treated cervical carcinoma in situ without current evidence of disease. * The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions: * Clinically significant or uncontrolled cardiac disease, including unstable angina, acute myocardial infarction within 6 months of enrollment, New York Heart Association (NYHA) Class III or IV congestive heart failure, circulatory collapse requiring vasopressor or inotropic support, or an arrhythmia that requires therapy. * A clinically significant respiratory disease that requires mechanical ventilation support or ≥ 50% oxygen. * Any uncontrolled active systemic infection or active infection requiring systemic treatment that was ongoing ≤ 7 days before screening. Subjects with acute infections requiring treatment should delay screening/enrollment until the course of therapy has been completed and the event is considered resolved. Prophylactic antibiotics will be permitted. * Cholestatic disorders, or unresolved sinusoidal obstructive syndrome/ veno-occlusive disease of the liver (defined as persistent total bilirubin \> 2 mg/dL, or abnormalities not attributable to GVHD and ongoing organ dysfunction). * History of thromboembolic event within 1 month before study registration. * HIV-infected patients on effective antiretroviral therapy with an undetectable viral load within 6 months are eligible for this trial. * Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection that requires treatment, or at risk for HBV reactivation (i.e., positive HBsAg). Participants with negative HBsAg and positive total hepatitis B core antigen (HBc) antibody may be included if HBV DNA is undetectable at the time of screening. Participants who are positive for HCV antibodies are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA. Participants whose immune status is unknown or uncertain must have results confirming immune status before enrollment. Serology results performed less than or equal to 6 months prior to the first planned dose of itacitinib are acceptable for determining eligibility. * Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v5.0 Grade ≥ 3). * Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug/treatment and attending required study visits; pose a significant risk to the participant; or interfere with the interpretation of study data. * Unable to understand the purpose and risks of the study and to provide a signed and dated informed consent form (ICF) and authorization to use protected health information (in accordance with national and local subject privacy regulations) per the investigator's assessment.