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

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ClinicalTrials.gov Identifier: NCT01713400
Recruitment Status : Completed
First Posted : October 24, 2012
Results First Posted : September 10, 2015
Last Update Posted : March 4, 2020
Sponsor:
Collaborator:
Gateway for Cancer Research
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute

Tracking Information
First Submitted Date  ICMJE October 22, 2012
First Posted Date  ICMJE October 24, 2012
Results First Submitted Date  ICMJE July 15, 2015
Results First Posted Date  ICMJE September 10, 2015
Last Update Posted Date March 4, 2020
Actual Study Start Date  ICMJE February 25, 2013
Actual Primary Completion Date October 27, 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 10, 2015)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: October 23, 2012)
Treg/total CD4+ ratio [ Time Frame: 30 days post transplant ]
Treg/total CD4+ ratio at day 30 following HCT
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 10, 2015)
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.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 23, 2012)
Incidence of Acute Graft vs. Host Disease [ Time Frame: 100 days post transplant ]
Incidence of acute graft vs. host disease will be characterized weekly from day of transplant to day 100 using the 1995 updated grading scheme for GVHD developed by Glucksberg, et al.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Tacrolimus, Sirolimus and Ustekinumab vs. Tacrolimus and Sirolimus for the Prevention of Acute Graft-Versus-Host Disease
Official Title  ICMJE Tacrolimus, Sirolimus and Ustekinumab vs. Tacrolimus and Sirolimus for the Prevention of Acute Graft-Versus-Host Disease Following Allogeneic Hematopoietic Cell Transplantation
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Graft vs. Host Disease
Intervention  ICMJE
  • Drug: Ustekinumab
    One subcutaneous injection administered on day -1 and repeated on day +20 after transplant
    Other Name: STELARA
  • 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
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: Ustekinumab
    • Drug: Tacrolimus (TAC)
    • Drug: Sirolimus
  • 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.
    Interventions:
    • Drug: Placebo
    • Drug: Tacrolimus (TAC)
    • Drug: Sirolimus
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 27, 2014)
54
Original Estimated Enrollment  ICMJE
 (submitted: October 23, 2012)
38
Actual Study Completion Date  ICMJE June 14, 2018
Actual Primary Completion Date October 27, 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01713400
Other Study ID Numbers  ICMJE MCC-16743
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party H. Lee Moffitt Cancer Center and Research Institute
Study Sponsor  ICMJE H. Lee Moffitt Cancer Center and Research Institute
Collaborators  ICMJE Gateway for Cancer Research
Investigators  ICMJE
Principal Investigator: Joseph Pidala, MD, MS H. Lee Moffitt Cancer Center and Research Institute
PRS Account H. Lee Moffitt Cancer Center and Research Institute
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP