Tacrolimus, Sirolimus and Ustekinumab vs. Tacrolimus and Sirolimus for the Prevention of Acute Graft-Versus-Host Disease
Condition: Graft vs. Host Disease
MeSH terms: Graft vs Host Disease
Intervention: Ustekinumab; Placebo; Tacrolimus (TAC); Sirolimus
Intervention description: One subcutaneous injection administered on day -1 and repeated on day +20 after transplant; Subcutaneous injection of sterile saline (identical volume to that of ustekinumab) administered via the identical route and schedule as ustekinumab.; Administered starting day -3 according to Blood and Marrow Transplant (BMT) Program standard operating procedures. TAC levels to be monitored and maintained at a target range of 3-7 given concurrent administration with sirolimus. Specific dose adjustments within this therapeutic range to be determined by the treating physician.; Administered initially as an oral loading dose on day -1. Thereafter, SIR to be administered as an oral regimen daily. The dose for both loading and ongoing administration to be dictated by the standard operating procedures of the BMT program. SIR levels to be monitored according to standard procedures. Dose adjustments to be made according to drug levels, with target range of 5-14ng/mL (therapeutic range by Abbott Architect instrument at Moffitt).
Intervention MeSH terms: Sirolimus; Ustekinumab; Tacrolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 54.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Acute Graft vs. Host Disease (aGVHD); Graft vs. Host Disease (GVHD)

Summary:

      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).
    

Eligibility criteria:

        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