Tildrakizumab for Prevention of Acute Graft-Versus-Host Disease

Inclusion Criteria: 1. Age ≥18 years. 2. Patients with any hematologic malignancy for which alloHCT is indicated. Patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) must be in complete remission at the time of alloHCT (\<5% blasts in the bone marrow, normal maturation of all cellular components in the bone marrow and absence of extramedullary disease). Patients with myelodysplastic syndrome (MDS) must have \<10% blasts in the bone marrow, no circulating blasts. 3. Myeloablative conditioning (MAC) regimen, based on Center for International Blood and Marrow Transplant Research (CIBMTR) criteria (total body irradiation (TBI) ≥5 Gy single dose or ≥8 Gy fractionated or busulfan \[Bu\] dose \>8 mg/kg oral or \>6.4 mg/kg intravenous). 4. T cell-replete peripheral blood graft. 5. Patients must have a matched related or unrelated donor (at least 6/6 match at human leukocyte antigen (HLA) -A, -B and -C for related donors and at least 8/8 match at HLA -A, -B, -C and -DRB1 for unrelated donors). 6. Cardiac function: Left ventricular ejection fraction ≥45% for myeloablative conditioning. 7. Estimated creatinine clearance ≥40 mL/minute (using the Cockcroft-Gault formula and actual body weight). 8. Pulmonary function: diffusing capacity of the lungs for carbon monoxide (DLCO) ≥40% (adjusted for hemoglobin) and forced expiratory volume in 1 second (FEV1) ≥50%. 9. Liver function: total bilirubin \<3 x upper limit of normal and alanine aminotransferase (ALT) / aspartate aminotransferase (AST) \<5 x upper normal limit. 10. Female subjects must meet one of the following: Postmenopausal for at least one year before enrollment, OR 1. Surgically sterile (i.e. undergone a hysterectomy or bilateral oophorectomy), OR 2. If subject is of childbearing potential (defined as not satisfying either of the above two criteria), she must agree to practice two acceptable methods of contraception (combination methods require use of two of the following: diaphragm with spermicide, cervical cap with spermicide, contraceptive sponge, male or female condom, hormonal contraceptive) from the time of signing of the informed consent form through 90 days after the last dose of study agent, OR 3. Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, post ovulation methods\] and withdrawal are not acceptable contraception methods.) 11. Male subjects, even if surgically sterilized (i.e., status post vasectomy), must agree to one of the following: 1. Practice effective barrier contraception during the entire study period and through 60 calendar days after the last dose of study agent, OR 2. Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, post ovulation methods\] and withdrawal are not acceptable methods of contraception.) 12. Signed informed consent: Voluntary written consent must be given before patient registration and performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care. 13. Planned post-transplant maintenance therapy is allowed. 14. Prior autologous transplant is allowed. Exclusion Criteria: 1. Prior allogeneic hematopoietic cell transplant (HCT). 2. Active central nervous system (CNS) involvement with malignancy. 3. Patients receiving cord blood or haploidentical allograft. 4. Patients undergoing in vivo or ex vivo T cell-depleted alloHCT. 5. Karnofsky Performance Score \<60% or Eastern Cooperative Oncology Group (ECOG) \> or = 2. 6. Patients with uncontrolled bacterial, viral or fungal infections (currently on treatment and with progression of infectious disease or no clinical improvement) at time of enrollment. 7. Active hepatitis B or C virus infection or known human immunodeficiency virus (HIV) positive. 8. Use of rituximab, alemtuzumab, anti-thymocyte globulin (ATG) or other monoclonal antibody planned as part of conditioning regimen for GVHD prophylaxis. 9. Participation in another GVHD prophylaxis clinical trial. 10. Any current uncontrolled cardiovascular conditions, including uncontrolled ventricular arrhythmias, New York Heart Association (NYHA) class III or IV congestive heart failure, uncontrolled angina, or electrocardiographic evidence of active ischemia or active conduction system abnormalities. 11. Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.