Graft vs. Host DiseasePhase 2UstekinumabNCT01713400
Tacrolimus, Sirolimus and Ustekinumab vs. Tacrolimus and Sirolimus for the Prevention of Acute Graft-Versus-Host Disease
A Phase 2 study testing Ustekinumab, Tacrolimus (TAC) and Sirolimus in people with Graft vs. Host Disease, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Graft vs. Host Disease
- What is being tested?
- Ustekinumab, Tacrolimus (TAC) and Sirolimus
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 54 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Feb 2013to 14 Jun 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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%.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, 33612
About this study
Official title: 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).
Read the 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.
- Conditions
- Graft vs. Host Disease
- Being tested
- Ustekinumab, Placebo, Tacrolimus (TAC), Sirolimus
- Keywords
- Acute Graft vs. Host Disease (aGVHD), Graft vs. Host Disease (GVHD)
- Medical subject headings
- Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UstekinumabDrug
Also called STELARA
One subcutaneous injection administered on day -1 and repeated on day +20 after transplant
PlaceboDrug
Also called saline
Subcutaneous injection of sterile saline (identical volume to that of ustekinumab) administered via the identical route and schedule as ustekinumab.
Tacrolimus (TAC)Drug
Also called TAC, Protopic, Prograf, Hecoria
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.
SirolimusDrug
Also called SIR, Rapamune
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).
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Placebo; Drug: Tacrolimus (TAC); Drug: Sirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 30 days post transplant
Secondary outcomes (1)
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.
Measured: 100 days post transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2012 (estimated)
- Study start25 Feb 2013
- Primary completion27 Oct 2014
- Study completion14 Jun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Graft vs. Host DiseaseStudies of the same condition, open and under way.
- More trials run by H. Lee Moffitt Cancer Center and Research InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Gateway for Cancer Research
- Responsible party
- Sponsor
- Investigators
- Joseph Pidala, MD, MS, Principal investigator, H. Lee Moffitt Cancer Center and Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01713400
- Sponsor's protocol ID
- MCC-16743
- Acronym
- Ustekinumab
- Status last verified
- Mar 2020
- First submitted
- 22 Oct 2012
- Last updated
- 4 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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.
PubMed 29242294
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tacrolimus, Sirolimus and Ustekinumab vs. Tacrolimus and Sirolimus for the Prevention of Acute Graft-Versus-Host Disease Following Allogeneic Hematopoietic Cell Transplantation
- ClinicalTrials.gov ID
- NCT01713400
- Acronym / sponsor ID
- Ustekinumab / MCC-16743
- Conditions
- Graft vs. Host Disease
- Keywords
- Acute Graft vs. Host Disease (aGVHD), Graft vs. Host Disease (GVHD)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Collaborators
- Gateway for Cancer Research
- Study start
- 25 Feb 2013 (actual)
- Primary completion
- 27 Oct 2014 (actual)
- Study completion
- 14 Jun 2018 (actual)
- First posted
- 24 Oct 2012 (estimated)
- Results
- Posted 10 Sep 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ustekinumab | Experimental | Drug: Ustekinumab, Drug: Tacrolimus (TAC), Drug: SirolimusUstekinumab, 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 | Placebo comparator | Drug: Placebo, Drug: Tacrolimus (TAC), Drug: SirolimusPlacebo, 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. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| UstekinumabAlso: STELARAOne subcutaneous injection administered on day -1 and repeated on day +20 after transplant | Drug | Ustekinumab |
| PlaceboAlso: salineSubcutaneous injection of sterile saline (identical volume to that of ustekinumab) administered via the identical route and schedule as ustekinumab. | Drug | Placebo |
| Tacrolimus (TAC)Also: TAC, Protopic, Prograf, HecoriaAdministered 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. | Drug | Placebo, Ustekinumab |
| SirolimusAlso: SIR, RapamuneAdministered 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). | Drug | Placebo, Ustekinumab |
Primary outcome
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.
1 secondary outcome
Incidence of Acute Graft vs. Host Disease (AGVHD)
Time frame: 100 days post transplant
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29242294Pidala 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.
- H. Lee Moffitt Cancer Center \& Research InstituteLink provided by the sponsor.
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Graft vs Host Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joseph Pidala, MD, MS principal investigator
H. Lee Moffitt Cancer Center and Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ustekinumab, Tacrolimus (TAC) and Sirolimus in people with Graft vs. Host Disease, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Sep 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
T Regulatory Cell (Treg)/Total Cluster of Differentiation 4 (CD4)+ Ratio (time frame: 30 days post transplant). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01713400, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2020.