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

Following reduced intensity conditioning and 8/8-matched peripheral blood transplant on Day 0, all patients will receive a GVHD prophylaxis post-transplant composed of the following: (i) cyclophosphamide administered at 25 mg/kg on Day +3 and +4, (ii) tacrolimus beginning on Day +5 and through Day +180 and administered with a trough target of 5-10 ng/ml through Day +90 and tapered thereafter; (iii) mycophenolate mofetil (MMF) administered at 15 mg/kg thrice daily beginning on Day +5 through Day +35; and (iv) ruxolitinib administered at 5 mg twice daily starting after engraftment (between Days +30 and +60) and continuing through one year post transplant.

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 transplant
• Patients must have a related or unrelated peripheral blood stem cell donor that is an 8/8 match at HLA-A, -B, -C and -DRB1 at high resolution using DNA-based typing. Unrelated donors must be willing to donate peripheral blood stem cells and meet NMDP criteria for donation.
• 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.