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

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