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

Graft vs. Host Disease Clinical Trial

— Ustekinumab  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01713400
• Other study ID #: MCC-16743
• Status: Completed
• Phase: Phase 2
• Start date: February 25, 2013
• Est. completion date: June 14, 2018

Study information

• Verified date: March 2020
• Source: H. Lee Moffitt Cancer Center and Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: June 14, 2018
• Est. primary completion date: October 27, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Graft vs Host Disease
• Graft vs. Host Disease

Intervention

Drug:
• Ustekinumab
One subcutaneous injection administered on day -1 and repeated on day +20 after transplant
• Placebo
Subcutaneous injection of sterile saline (identical volume to that of ustekinumab) administered via the identical route and schedule as ustekinumab.
• Tacrolimus (TAC)
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.
• Sirolimus
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).

Locations

Country	Name	City	State
United States	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
H. Lee Moffitt Cancer Center and Research Institute	Gateway for Cancer Research

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	T Regulatory Cell (Treg)/Total Cluster of Differentiation 4 (CD4)+ Ratio	Median Blood Treg/Total CD4+ Ratio at day 30 following hematopoietic cell transplantation (HCT). Comparison between study arms: Ustekinumab vs. Placebo. From NCI Dictionary: "T reg" - A type of immune cell that blocks the actions of some other types of lymphocytes, to keep the immune system from becoming over-active. T regs are being studied in the treatment of cancer. A T reg is a type of white blood cell and a type of lymphocyte. Also called regulatory T cell, suppressor T cell, and T-regulatory cell.	30 days post transplant
Secondary	Incidence of Acute Graft vs. Host Disease (AGVHD)	Cumulative incidence of Grade II - IV AGVHD to be characterized weekly from day of transplant to day 100 using the 1995 updated grading scheme for Graft vs. Host Disease (GVHD) developed by Glucksberg, et al.	100 days post transplant

External Links

•   H. Lee Moffitt Cancer Center & Research Institute