Clinical trial NCT01713400: Tacrolimus, Sirolimus and Ustekinumab vs. Tacrolimus and Sirolimus for the Prevention of Acute Graft-Versus-Host Disease
Official title: Tacrolimus, Sirolimus and Ustekinumab vs. Tacrolimus and Sirolimus for the Prevention of Acute Graft-Versus-Host Disease Following Allogeneic Hematopoietic Cell Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Graft vs. Host Disease
Keywords: Acute Graft vs. Host Disease (aGVHD)
Graft vs. Host Disease (GVHD)
Lead sponsor: H. Lee Moffitt Cancer Center and Research Institute
Sponsor class: OTHER
Collaborators: name: Gateway for Cancer Research
First posted: 2012-10-24
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

Detailed description: 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.

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

Primary outcomes:
measure: T Regulatory Cell (Treg)/Total Cluster of Differentiation 4 (CD4)+ Ratio
timeFrame: 30 days post transplant
Secondary outcomes:
measure: Incidence of Acute Graft vs. Host Disease (AGVHD)
timeFrame: 100 days post transplant
Other outcomes:
Locations:
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute
state: Florida
Study officials:
affiliation: H. Lee Moffitt Cancer Center and Research Institute
name: Joseph Pidala, MD, MS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pidala J, Beato F, Kim J, Betts B, Jim H, Sagatys E, Levine JE, Ferrara JLM, Ozbek U, Ayala E, Davila M, Fernandez HF, Field T, Kharfan-Dabaja MA, Khaira D, Khimani F, Locke FL, Mishra A, Nieder M, Nishihori T, Perez L, Riches M, Anasetti C. In vivo IL-12/IL-23p40 neutralization blocks Th1/Th17 response after allogeneic hematopoietic cell transplantation. Haematologica. 2018 Mar;103(3):531-539. doi: 10.3324/haematol.2017.171199. Epub 2017 Dec 14.