Trial Outcomes & Findings for Tacrolimus, Sirolimus and Ustekinumab vs. Tacrolimus and Sirolimus for the Prevention of Acute Graft-Versus-Host Disease (NCT NCT01713400)
NCT ID: NCT01713400
Last Updated: 2020-03-04
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
54 participants
Primary outcome timeframe
30 days post transplant
Results posted on
2020-03-04
Participant Flow
54 participants (potential donors and recipients) were enrolled at Moffitt Cancer Center from 3/15/2013 through 5/22/2014.
30 eligible recipients were randomly assigned 1:1 (Ustekinumab n=15, Placebo n=15) with stratification for donor type. Results Data pertains to recipients only.
Participant milestones
| Measure |
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.
|
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.
|
|---|---|---|
|
Overall Study
STARTED
|
15
|
15
|
|
Overall Study
COMPLETED
|
15
|
15
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Tacrolimus, Sirolimus and Ustekinumab vs. Tacrolimus and Sirolimus for the Prevention of Acute Graft-Versus-Host Disease
Baseline characteristics by cohort
| Measure |
Ustekinumab
n=15 Participants
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.
|
Placebo
n=15 Participants
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.
|
Total
n=30 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
13 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
2 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
15 participants
n=5 Participants
|
15 participants
n=7 Participants
|
30 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 30 days post transplantPopulation: All participating recipients
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.
Outcome measures
| Measure |
Ustekinumab
n=15 Participants
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.
|
Placebo
n=15 Participants
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.
|
|---|---|---|
|
T Regulatory Cell (Treg)/Total Cluster of Differentiation 4 (CD4)+ Ratio
|
13 ratio
Interval 2.0 to 22.0
|
11 ratio
Interval 3.0 to 20.0
|
SECONDARY outcome
Timeframe: 100 days post transplantPopulation: All participating recipients
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.
Outcome measures
| Measure |
Ustekinumab
n=15 Participants
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.
|
Placebo
n=15 Participants
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.
|
|---|---|---|
|
Incidence of Acute Graft vs. Host Disease (AGVHD)
|
33.3 percentage of participants
|
40.0 percentage of participants
|
Adverse Events
Ustekinumab
Serious events: 4 serious events
Other events: 8 other events
Deaths: 0 deaths
Placebo
Serious events: 4 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Ustekinumab
n=15 participants at risk
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.
|
Placebo
n=15 participants at risk
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.
|
|---|---|---|
|
Blood and lymphatic system disorders
Blood and lymphatic system disorders - Other, TMA
|
0.00%
0/15 • 1 year, 6 months
|
6.7%
1/15 • Number of events 1 • 1 year, 6 months
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/15 • 1 year, 6 months
|
6.7%
1/15 • Number of events 1 • 1 year, 6 months
|
|
Cardiac disorders
Cardiac disorders - Other, Hypotension
|
0.00%
0/15 • 1 year, 6 months
|
6.7%
1/15 • Number of events 1 • 1 year, 6 months
|
|
Gastrointestinal disorders
Gastric hemorrhage
|
6.7%
1/15 • Number of events 1 • 1 year, 6 months
|
0.00%
0/15 • 1 year, 6 months
|
|
Gastrointestinal disorders
Gastrointestinal disorders - Other, Acute cholecystitis
|
6.7%
1/15 • Number of events 1 • 1 year, 6 months
|
0.00%
0/15 • 1 year, 6 months
|
|
Gastrointestinal disorders
Gastrointestinal disorders - Other, GVHD of gut
|
0.00%
0/15 • 1 year, 6 months
|
6.7%
1/15 • Number of events 1 • 1 year, 6 months
|
|
Hepatobiliary disorders
Hepatobiliary disorders - Other, VOD
|
13.3%
2/15 • Number of events 2 • 1 year, 6 months
|
6.7%
1/15 • Number of events 2 • 1 year, 6 months
|
|
Hepatobiliary disorders
Portal hypertension
|
13.3%
2/15 • Number of events 2 • 1 year, 6 months
|
0.00%
0/15 • 1 year, 6 months
|
|
Infections and infestations
Bladder infection
|
6.7%
1/15 • Number of events 1 • 1 year, 6 months
|
0.00%
0/15 • 1 year, 6 months
|
|
Infections and infestations
Infections and infestations - Other, HHV6 infection affecting CNS
|
0.00%
0/15 • 1 year, 6 months
|
6.7%
1/15 • Number of events 1 • 1 year, 6 months
|
|
Infections and infestations
Skin infection
|
0.00%
0/15 • 1 year, 6 months
|
6.7%
1/15 • Number of events 1 • 1 year, 6 months
|
|
Psychiatric disorders
Confusion
|
0.00%
0/15 • 1 year, 6 months
|
6.7%
1/15 • Number of events 1 • 1 year, 6 months
|
|
Psychiatric disorders
Hallucinations
|
6.7%
1/15 • Number of events 1 • 1 year, 6 months
|
0.00%
0/15 • 1 year, 6 months
|
|
Renal and urinary disorders
Acute kidney injury
|
0.00%
0/15 • 1 year, 6 months
|
6.7%
1/15 • Number of events 1 • 1 year, 6 months
|
|
Renal and urinary disorders
Renal and urinary disorders - Other, elevated creatinine
|
0.00%
0/15 • 1 year, 6 months
|
6.7%
1/15 • Number of events 1 • 1 year, 6 months
|
|
Renal and urinary disorders
Renal and urinary disorders - Other, renal failure-dialysis
|
0.00%
0/15 • 1 year, 6 months
|
6.7%
1/15 • Number of events 1 • 1 year, 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/15 • 1 year, 6 months
|
6.7%
1/15 • Number of events 1 • 1 year, 6 months
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other, GVHD of skin
|
0.00%
0/15 • 1 year, 6 months
|
6.7%
1/15 • Number of events 1 • 1 year, 6 months
|
Other adverse events
| Measure |
Ustekinumab
n=15 participants at risk
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.
|
Placebo
n=15 participants at risk
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.
|
|---|---|---|
|
Hepatobiliary disorders
Hepatobiliary disorders - Other
|
13.3%
2/15 • Number of events 2 • 1 year, 6 months
|
20.0%
3/15 • Number of events 4 • 1 year, 6 months
|
|
Gastrointestinal disorders
Mucositis oral
|
6.7%
1/15 • Number of events 5 • 1 year, 6 months
|
13.3%
2/15 • Number of events 8 • 1 year, 6 months
|
|
Gastrointestinal disorders
Diarrhea
|
6.7%
1/15 • Number of events 6 • 1 year, 6 months
|
13.3%
2/15 • Number of events 2 • 1 year, 6 months
|
|
Infections and infestations
Rhinitis infective
|
0.00%
0/15 • 1 year, 6 months
|
20.0%
3/15 • Number of events 3 • 1 year, 6 months
|
|
Infections and infestations
Upper respiratory infection
|
6.7%
1/15 • Number of events 3 • 1 year, 6 months
|
0.00%
0/15 • 1 year, 6 months
|
|
Infections and infestations
Urinary tract infection
|
6.7%
1/15 • Number of events 1 • 1 year, 6 months
|
0.00%
0/15 • 1 year, 6 months
|
|
Cardiac disorders
Cardiac disorders - Other
|
6.7%
1/15 • Number of events 1 • 1 year, 6 months
|
13.3%
2/15 • Number of events 7 • 1 year, 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Bronchopulmonary hemorrhage
|
6.7%
1/15 • Number of events 1 • 1 year, 6 months
|
0.00%
0/15 • 1 year, 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Laryngeal mucositis
|
0.00%
0/15 • 1 year, 6 months
|
6.7%
1/15 • Number of events 1 • 1 year, 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders - Other
|
6.7%
1/15 • Number of events 1 • 1 year, 6 months
|
0.00%
0/15 • 1 year, 6 months
|
|
Blood and lymphatic system disorders
Blood and lymphatic disorders - Other
|
6.7%
1/15 • Number of events 1 • 1 year, 6 months
|
6.7%
1/15 • Number of events 1 • 1 year, 6 months
|
|
Investigations
Alanine aminotransferase increased
|
6.7%
1/15 • Number of events 6 • 1 year, 6 months
|
6.7%
1/15 • Number of events 1 • 1 year, 6 months
|
|
Investigations
Alkaline phosphatase increased
|
6.7%
1/15 • Number of events 1 • 1 year, 6 months
|
6.7%
1/15 • Number of events 6 • 1 year, 6 months
|
|
Investigations
Aspartate aminotransferase increased
|
6.7%
1/15 • Number of events 4 • 1 year, 6 months
|
6.7%
1/15 • Number of events 5 • 1 year, 6 months
|
|
Investigations
Blood bilirubin increased
|
6.7%
1/15 • Number of events 3 • 1 year, 6 months
|
0.00%
0/15 • 1 year, 6 months
|
|
Investigations
GGT increased
|
6.7%
1/15 • Number of events 2 • 1 year, 6 months
|
0.00%
0/15 • 1 year, 6 months
|
|
Vascular disorders
Hypertension
|
13.3%
2/15 • Number of events 2 • 1 year, 6 months
|
0.00%
0/15 • 1 year, 6 months
|
|
Nervous system disorders
Headache
|
6.7%
1/15 • Number of events 1 • 1 year, 6 months
|
0.00%
0/15 • 1 year, 6 months
|
Additional Information
Dr. Joseph Pidala
H. Lee Moffitt Cancer Center and Research Institute
Phone: 813-745-2556
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place