Tacrolimus, Sirolimus and Ustekinumab vs. Tacrolimus and Sirolimus for the Prevention of Acute Graft-Versus-Host Disease

Tacrolimus, Sirolimus and Ustekinumab vs. Tacrolimus and Sirolimus for the Prevention of Acute Graft-Versus-Host Disease Following Allogeneic Hematopoietic Cell Transplantation

To determine whether treatment with ustekinumab will alter the ratio of T Regulatory Cell (Treg)/total cluster of differentiation 4 (CD4)+ cells in peripheral blood at day 30 post-hematopoietic cell transplantation (HCT).

This is a comparative study to assess the biologic and clinical activity of the agent ustekinumab when given in concert with our established regimen of SIR/TAC. Patients will be randomly assigned between the standard regimen of tacrolimus/sirolimus (TAC/SIR + placebo) vs. the investigational regimen of tacrolimus/sirolimus/ustekinumab (TAC/SIR/U) in a 1:1 scheme.

Inclusion Criteria:

• Hematologic disorder requiring allogeneic hematopoietic cell transplantation
• Adequate vital organ function:
• Left ventricular ejection fraction (LVEF) >/= 45% by multigated acquisition (MUGA) scan
• FEV1, FVC, and diffusing lung capacity oxygenation (DLCO) >/= 50% of predicted values on pulmonary function tests
• Transaminases (AST, ALT) < 3 times upper limit of normal values
• Creatinine clearance >/= 50 cc/min.
• Performance status: Karnofsky Performance Status Score >/= 60%.

Exclusion Criteria:

• Active infection not controlled with appropriate antimicrobial therapy
• HIV, hepatitis B, or hepatitis C infection
• Sorror's co-morbidity factors with total score > 3
• Important modification to co-morbidity index calculation: DLCO will not be included in assessment of pulmonary risk, excepting those with DLCO < 50%, who will merit a score of 3 and thereby be excluded from the trial.
• Anti-thymocyte globulin (ATG) as part of the conditioning regimen
• Cyclophosphamide as part of the conditioning regimens