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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Gateway for Cancer Research
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:
NCT01713400
First received: October 22, 2012
Last updated: May 6, 2016
Last verified: May 2016
  Purpose
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).

Condition Intervention Phase
Graft vs. Host Disease
Drug: Ustekinumab
Drug: Placebo
Drug: Tacrolimus (TAC)
Drug: Sirolimus
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Tacrolimus, Sirolimus and Ustekinumab vs. Tacrolimus and Sirolimus for the Prevention of Acute Graft-Versus-Host Disease Following Allogeneic Hematopoietic Cell Transplantation

Resource links provided by NLM:


Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:

Primary Outcome Measures:
  • T Regulatory Cell (Treg)/Total Cluster of Differentiation 4 (CD4)+ Ratio [ Time Frame: 30 days post transplant ] [ Designated as safety issue: No ]
    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) [ Time Frame: 100 days post transplant ] [ Designated as safety issue: No ]
    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.


Enrollment: 54
Study Start Date: February 2013
Estimated Study Completion Date: December 2016
Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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
  • Protopic
  • Prograf
  • Hecoria
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: Placebo
Subcutaneous injection of sterile saline (identical volume to that of ustekinumab) administered via the identical route and schedule as ustekinumab.
Other Name: saline
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
  • Protopic
  • Prograf
  • Hecoria
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

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

Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01713400

Locations
United States, Florida
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, United States, 33612
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Gateway for Cancer Research
Investigators
Principal Investigator: Joseph Pidala, MD, MS H. Lee Moffitt Cancer Center and Research Institute
  More Information

Additional Information:
Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT01713400     History of Changes
Other Study ID Numbers: MCC-16743 
Study First Received: October 22, 2012
Results First Received: July 15, 2015
Last Updated: May 6, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
Acute Graft vs. Host Disease (aGVHD)
Graft vs. Host Disease (GVHD)

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases
Tacrolimus
Sirolimus
Everolimus
Ustekinumab
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Dermatologic Agents

ClinicalTrials.gov processed this record on September 23, 2016