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

NCT01713400 | Completed Phase 2 Results DMC

• 1 other identifier: MCC-16743
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

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).

Conditions

Graft vs. Host Disease

Keywords

Acute Graft vs. Host Disease (aGVHD); Graft vs. Host Disease (GVHD)

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Incidence of Acute Graft vs. Host Disease (AGVHD)

  100 days post transplant

Study Arms (2)

Ustekinumab

EXPERIMENTAL

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; Drug: Tacrolimus (TAC); Drug: Sirolimus

Placebo

PLACEBO COMPARATOR

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; Drug: Tacrolimus (TAC); Drug: Sirolimus

Interventions

Ustekinumab DRUG

One subcutaneous injection administered on day -1 and repeated on day +20 after transplant

Also known as: STELARA

Ustekinumab

Placebo DRUG

Subcutaneous injection of sterile saline (identical volume to that of ustekinumab) administered via the identical route and schedule as ustekinumab.

Also known as: saline

Placebo

Tacrolimus (TAC) DRUG

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.

Also known as: TAC, Protopic, Prograf, Hecoria

Placebo; Ustekinumab

Sirolimus DRUG

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).

Also known as: SIR, Rapamune

Placebo; Ustekinumab

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%.

You may not qualify if:

• 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

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Gateway for Cancer Research: collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

Related Publications (1)

• 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.

  PMID: 29242294 DERIVED

Related Links

• H. Lee Moffitt Cancer Center \& Research Institute

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

Ustekinumab; Sodium Chloride; Tacrolimus; Sirolimus

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Dr. Joseph Pidala
• Organization: H. Lee Moffitt Cancer Center and Research Institute

joseph.pidala@moffitt.org

813-745-2556

Study Officials

• Joseph Pidala, MD, MS

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2012
• First Posted: October 24, 2012
• Study Start: February 25, 2013
• Primary Completion: October 27, 2014
• Study Completion: June 14, 2018
• Last Updated: March 4, 2020
• Results First Posted: September 10, 2015

Record last verified: 2020-03

Locations

US (1)