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

Primary Purpose

Graft vs. Host Disease

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Ustekinumab
Placebo
Tacrolimus (TAC)
Sirolimus
Sponsored by
H. Lee Moffitt Cancer Center and Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Graft vs. Host Disease focused on measuring Acute Graft vs. Host Disease (aGVHD), Graft vs. Host Disease (GVHD)

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • H. Lee Moffitt Cancer Center & Research Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Ustekinumab

Placebo

Arm Description

Ustekinumab, Tacrolimus and Sirolimus. Ustekinumab: 45 mg for adults who weight 100 kg or less; 90 mg for adults who weight greater than 100 kg. Tacrolimus: Level determined according to Blood and Marrow Transplant (BMT) Program standard operating procedures. Sirolimus: The dose for both loading and ongoing administration to be dictated by the standard operating procedures of the BMT program.

Placebo, Tacrolimus, and Sirolimus. Placebo: Identical volume to that of ustekinumab. Tacrolimus: Level determined according to Blood and Marrow Transplant (BMT) Program standard operating procedures. Sirolimus: The dose for both loading and ongoing administration to be dictated by the standard operating procedures of the BMT program.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

First Posted
October 22, 2012
Last Updated
March 2, 2020
Sponsor
H. Lee Moffitt Cancer Center and Research Institute
Collaborators
Gateway for Cancer Research
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1. Study Identification

Unique Protocol Identification Number
NCT01713400
Brief Title
Tacrolimus, Sirolimus and Ustekinumab vs. Tacrolimus and Sirolimus for the Prevention of Acute Graft-Versus-Host Disease
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
February 25, 2013 (Actual)
Primary Completion Date
October 27, 2014 (Actual)
Study Completion Date
June 14, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
H. Lee Moffitt Cancer Center and Research Institute
Collaborators
Gateway for Cancer Research

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Graft vs. Host Disease
Keywords
Acute Graft vs. Host Disease (aGVHD), Graft vs. Host Disease (GVHD)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
54 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Ustekinumab
Arm Type
Experimental
Arm Description
Ustekinumab, Tacrolimus and Sirolimus. Ustekinumab: 45 mg for adults who weight 100 kg or less; 90 mg for adults who weight greater than 100 kg. Tacrolimus: Level determined according to Blood and Marrow Transplant (BMT) Program standard operating procedures. Sirolimus: The dose for both loading and ongoing administration to be dictated by the standard operating procedures of the BMT program.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo, Tacrolimus, and Sirolimus. Placebo: Identical volume to that of ustekinumab. Tacrolimus: Level determined according to Blood and Marrow Transplant (BMT) Program standard operating procedures. Sirolimus: The dose for both loading and ongoing administration to be dictated by the standard operating procedures of the BMT program.
Intervention Type
Drug
Intervention Name(s)
Ustekinumab
Other Intervention Name(s)
STELARA
Intervention Description
One subcutaneous injection administered on day -1 and repeated on day +20 after transplant
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
saline
Intervention Description
Subcutaneous injection of sterile saline (identical volume to that of ustekinumab) administered via the identical route and schedule as ustekinumab.
Intervention Type
Drug
Intervention Name(s)
Tacrolimus (TAC)
Other Intervention Name(s)
TAC, Protopic, Prograf, Hecoria
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Sirolimus
Other Intervention Name(s)
SIR, Rapamune
Intervention Description
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).
Primary Outcome Measure Information:
Title
T Regulatory Cell (Treg)/Total Cluster of Differentiation 4 (CD4)+ Ratio
Description
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.
Time Frame
30 days post transplant
Secondary Outcome Measure Information:
Title
Incidence of Acute Graft vs. Host Disease (AGVHD)
Description
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.
Time Frame
100 days post transplant

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joseph Pidala, MD, MS
Organizational Affiliation
H. Lee Moffitt Cancer Center and Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
H. Lee Moffitt Cancer Center & Research Institute
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
29242294
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.
Results Reference
derived
Links:
URL
http://www.moffitt.org/
Description
H. Lee Moffitt Cancer Center & Research Institute

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

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