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

March 2, 2020 updated by: H. Lee Moffitt Cancer Center and Research Institute

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

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

54

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Tampa, Florida, United States, 33612
        • H. Lee Moffitt Cancer Center & Research Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 68 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ustekinumab
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.
Drug: Ustekinumab
One subcutaneous injection administered on day -1 and repeated on day +20 after transplant
Other Names:
  • STELARA
Drug: 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.
Other Names:
  • TAC
  • Prograf
  • Hecoria
  • Protopic
Drug: 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).
Other Names:
  • SIR
  • Rapamune
Placebo Comparator: Placebo
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.
Drug: 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.
Other Names:
  • TAC
  • Prograf
  • Hecoria
  • Protopic
Drug: 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).
Other Names:
  • SIR
  • Rapamune
Drug: Placebo
Subcutaneous injection of sterile saline (identical volume to that of ustekinumab) administered via the identical route and schedule as ustekinumab.
Other Names:
  • saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
T Regulatory Cell (Treg)/Total Cluster of Differentiation 4 (CD4)+ Ratio
Time Frame: 30 days post transplant
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Acute Graft vs. Host Disease (AGVHD)
Time Frame: 100 days post transplant
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

H. Lee Moffitt Cancer Center and Research Institute

Collaborators

Gateway for Cancer Research

Investigators

  • Principal Investigator: Joseph Pidala, MD, MS, H. Lee Moffitt Cancer Center and Research Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 25, 2013

Primary Completion (Actual)

October 27, 2014

Study Completion (Actual)

June 14, 2018

Study Registration Dates

First Submitted

October 22, 2012

First Submitted That Met QC Criteria

October 23, 2012

First Posted (Estimate)

October 24, 2012

Study Record Updates

Last Update Posted (Actual)

March 4, 2020

Last Update Submitted That Met QC Criteria

March 2, 2020

Last Verified

March 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MCC-16743

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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