De-escalated Cyclophosphamide (PTCy) and Ruxolitinib for Graft-versus-Host Disease (GVHD) Prophylaxis

This is an open-label phase 2 study designed to explore the efficacy and safety of low-dose PTCy-ruxolitinib GVHD prophylaxis in older adults undergoing allogeneic HCT with a matched sibling or unrelated donor with a peripheral blood stem cell graft.

Inclusion Criteria:History of hematologic malignancy.Must be in remission:Acute Leukemia, chronic leukemia, or myelodysplasia/myeloproliferative neoplasm (excluding primary myelofibrosis): No circulating blasts and <5% blasts in the bone marrow.Hodgkin and non-Hodgkin lymphomas: Chemo-sensitive disease at time of transplantPlanned donor must be 8/8 human leukocyte antigen (HLA) -matched at HLA-A, -B, -DR, and -C.Graft source of peripheral blood.Planned reduced intensity conditioning therapy with fludarabine/melphalan, with total dose of melphalan of 100-140 mg/m^2 IV or fludarabine/busulfan with total dose of busulfan of 6.4 mg/kg IV.Karnofsky Performance Scale of 60 or greater.Male participants must agree to abstinence or to use of barrier contraception during the entire study period.Female participants of childbearing potential will require a negative pregnancy test and should agree to practice two effective methods of contraception during the entire study period.Ability to understand a written informed consent document, and the willingness to sign it.Exclusion Criteria:Prior allogeneic HCT or Chimeric antigen receptor (CAR) -T cell therapy.Patients with liver dysfunction evidenced by bilirubin ≥2x upper limit normal (ULN), except for a history of Gilbert syndrome.Patients with renal impairment defined by creatinine<2mg/dL.Patients with cardiac dysfunction defined by a left ventricular ejection fraction ≤45%.Patients with pulmonary dysfunction defined by a forced expiratory volume in the first second (FEV1) or diffusing capacity for carbon monoxide (DLCO) (corrected for hemoglobin) ≤50% of predicted.Patients with a chronic or active infection requiring systemic treatment during and after transplant.Presence of other active malignant disease diagnosed within 12 months, except for adequately treated non-melanoma skin cancer, adequately treated melanoma grade 2 or less, or cervical intraepithelial neoplasia. Active malignancy is malignancy receiving treatment.Pregnant or lactating subjects.