Baricitinib for the Prevention of Graft Versus Host Disease in Patients with Hematological Malignancies after Peripheral Blood Donor Stem Cell Transplantation

Inclusion Criteria

• Diagnosis of a hematological malignancy listed below: * Acute myelogenous leukemia (AML) in complete morphological remission (based on International Working Group [IWG] criteria) * Acute lymphocytic leukemia (ALL) in complete morphological remission (minimal residual disease [MRD] negative, based on IWG criteria) * Myelodysplastic syndrome with less than 10% blasts in bone marrow * Non-Hodgkin’s lymphoma (NHL) or Hodgkin’s disease (HD) in 2nd or greater complete or partial remission
• Planned treatment is myeloablative or reduced intensity conditioning followed by peripheral blood human leukocyte antigen (HLA) matched donor transplantation
• Available HLA-identical donor who meets the following criteria: * At least 18 years of age * HLA-identical donor/recipient match by high-resolution typing per institutional standards * In the investigator’s opinion, is in general good health, and medically able to tolerate leukapheresis required for harvesting hematopoietic stem cell (HSC) * No active hepatitis * Negative for human T-lymphotropic virus (HTLV) and human immunodeficiency virus (HIV) * Not pregnant * Donor selection will be in compliance with institutional standards * Safety lead-in phase: For the first three patients at each dose level, the donor must consent to a second product collection should it prove necessary
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Total bilirubin must be within normal range at baseline
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.0 x institutional upper limit of normal (IULN) (within 30 days prior to day 0)
• Estimated creatinine clearance >= 60 mL/min by Cockcroft-Gault formula (within 30 days prior to day 0)
• Oxygen saturation >= 90% on room air (within 30 days prior to day 0)
• Left ventricular ejection fraction (LVEF) >= 40% (within 30 days prior to day 0)
• Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) >= 40% predicted, diffusion capacity of the lung for carbon monoxide (DLCO) >= 40% predicted. If DLCO is < 40%, patients will still be considered eligible if deemed safe after a pulmonary evaluation (within 30 days prior to day 0)
• Able to understand and willing to sign an Institutional Review Board (IRB) approved written informed consent document (or that of legally authorized representative, if applicable)
• Must be able to receive GVHD prophylaxis with tacrolimus, mini-methotrexate with or without anti-thymocyte globulin (ATG) or post transplant cyclophosphamide (Cy) with mycophenolate mofetil (MMF) and tacrolimus

Exclusion Criteria

• Must not have undergone a prior allogeneic donor (related, unrelated, or cord) transplant. Prior autologous transplant is not exclusionary
• Known HIV or active hepatitis B or C infection
• Known latent tuberculosis infection, or at high risk for latent tuberculosis (TB) infection, or a positive t-spot tuberculosis test
• Known hypersensitivity to one or more of the study agents, including baricitinib
• Must not have myelofibrosis or other disease known to prolong neutrophil engraftment to > 35 days after transplant
• Currently receiving or has received any investigational drugs within the 14 days prior to the first dose of study drug (day -3)
• Pregnant and/or breastfeeding
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, autoimmune disease, symptomatic congestive heart failure, unstable angina pectoris, unstable cardiac arrhythmias, or psychiatric illness/social situations that would limit compliance with study requirements
• Immunosuppressive doses of steroids. Subjects with steroids for adrenal insufficiency will not be excluded
• History of unprovoked thrombosis or known thrombophilia. Provoked and/or superficial deep vein thrombosis (DVT)’s are eligible provided they are treated and resolved at the time of screening
• Recent (less than 1 year from screening) myocardial infarction or embolic stroke