Trial Outcomes & Findings for Sitagliptin for Prevention of Acute Graft Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation (NCT NCT02683525)
NCT ID: NCT02683525
Last Updated: 2021-01-22
Results Overview
Percent of patients and the 95% Confidence interval who did not have Grade II-IV Acute GvHD by 100 days following transplant. Since the study completed the two-phase design, proper inference was used to generate the confidence interval (Koyama and Chen). Only patients who were on the study for at least 100 days post transplant were included in the analysis.
COMPLETED
PHASE2
37 participants
up to 100 days
2021-01-22
Participant Flow
Participant milestones
| Measure |
Sitagliptin
Sitagliptin 600 mg q 12 hours PO starting on Day -1 before transplant to be administered between 8:00 am and 10:00 am then given every 12 hours (total 32 doses) through day +14.
Sitagliptin: 600 mg ever 12 hours by mouth will be given starting the day before transplant through day +14 after transplant
|
|---|---|
|
Overall Study
STARTED
|
37
|
|
Overall Study
COMPLETED
|
29
|
|
Overall Study
NOT COMPLETED
|
8
|
Reasons for withdrawal
| Measure |
Sitagliptin
Sitagliptin 600 mg q 12 hours PO starting on Day -1 before transplant to be administered between 8:00 am and 10:00 am then given every 12 hours (total 32 doses) through day +14.
Sitagliptin: 600 mg ever 12 hours by mouth will be given starting the day before transplant through day +14 after transplant
|
|---|---|
|
Overall Study
Lost to Follow-up
|
1
|
|
Overall Study
Physician Decision
|
1
|
|
Overall Study
Disease Progression
|
6
|
Baseline Characteristics
Sitagliptin for Prevention of Acute Graft Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation
Baseline characteristics by cohort
| Measure |
Sitagliptin
n=37 Participants
Sitagliptin 600 mg q 12 hours PO starting on Day -1 before transplant to be administered between 8:00 am and 10:00 am then given every 12 hours (total 32 doses) through day +14.
Sitagliptin: 600 mg ever 12 hours by mouth will be given starting the day before transplant through day +14 after transplant
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=39 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
37 Participants
n=39 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=39 Participants
|
|
Age, Continuous
|
45.5 years
STANDARD_DEVIATION 10.06 • n=39 Participants
|
|
Sex: Female, Male
Female
|
19 Participants
n=39 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=39 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=39 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
35 Participants
n=39 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=39 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=39 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=39 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=39 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=39 Participants
|
|
Race (NIH/OMB)
White
|
35 Participants
n=39 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=39 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=39 Participants
|
|
Disease Type
Acute Lymphoblastic Leukemia (ALL)
|
9 Participants
n=39 Participants
|
|
Disease Type
Acute Myeloid Leukemia (AML)
|
20 Participants
n=39 Participants
|
|
Disease Type
Chronic Myeloid Leukemia (CML)
|
4 Participants
n=39 Participants
|
|
Disease Type
Myelodysplasia (MDS)
|
4 Participants
n=39 Participants
|
PRIMARY outcome
Timeframe: up to 100 daysPopulation: Patients on study at least 100 days post-transplant
Percent of patients and the 95% Confidence interval who did not have Grade II-IV Acute GvHD by 100 days following transplant. Since the study completed the two-phase design, proper inference was used to generate the confidence interval (Koyama and Chen). Only patients who were on the study for at least 100 days post transplant were included in the analysis.
Outcome measures
| Measure |
Sitagliptin
n=36 Participants
Sitagliptin 600 mg q 12 hours PO starting on Day -1 before transplant to be administered between 8:00 am and 10:00 am then given every 12 hours (total 32 doses) through day +14.
Sitagliptin: 600 mg ever 12 hours by mouth will be given starting the day before transplant through day +14 after transplant
|
|---|---|
|
Percentage of Patients With Grade II-IV Acute GvHD by Day +100 Following Transplant
|
94.4 percentage of participants
Interval 82.0 to 97.1
|
SECONDARY outcome
Timeframe: 100 days from transplantPopulation: All patients who received a transplant
Kaplan-Meier methods will be used to conduct a competing risk analysis. Time until grade II-IV acute GvHD will be calculated from transplant until grade II-IV acute GvHD or death from GvHD. Patients who relapsed or died from causes other than GvHD will be considered a competing risk and calculated from time of transplant until relapse or death. Otherwise, patients will be censored and calculated from transplant until the last known alive date. The cumulative incidence percentage of grade II-IV acute GvHD at day +100 was calculated along with a 95% confidence interval.
Outcome measures
| Measure |
Sitagliptin
n=37 Participants
Sitagliptin 600 mg q 12 hours PO starting on Day -1 before transplant to be administered between 8:00 am and 10:00 am then given every 12 hours (total 32 doses) through day +14.
Sitagliptin: 600 mg ever 12 hours by mouth will be given starting the day before transplant through day +14 after transplant
|
|---|---|
|
Percentage of Patients With Grade II-IV Acute GvHD at Day +100
|
5.5 percentage of participants
Interval 1.0 to 16.3
|
SECONDARY outcome
Timeframe: up to 2 monthsPopulation: All patients who received a transplant.
Number of unique patients who had a treatment related (possible, probable or definite) non-hematological adverse event that was graded 3 or greater.
Outcome measures
| Measure |
Sitagliptin
n=37 Participants
Sitagliptin 600 mg q 12 hours PO starting on Day -1 before transplant to be administered between 8:00 am and 10:00 am then given every 12 hours (total 32 doses) through day +14.
Sitagliptin: 600 mg ever 12 hours by mouth will be given starting the day before transplant through day +14 after transplant
|
|---|---|
|
Number of Patients With Treatment Related Adverse Events Grade 3 or Higher for Non-hematological Toxicity
|
0 Participants
|
SECONDARY outcome
Timeframe: 100 days from transplantPopulation: All patients who received a transplant
Kaplan-Meier methods will be used to conduct a competing risk analysis. Time until grade III-IV acute GvHD will be calculated from transplant until grade III-IV acute GvHD or death from GvHD. Patients who relapsed or died from causes other than GvHD will be considered a competing risk and calculated from time of transplant until relapse or death. Otherwise, patients will be censored and calculated from transplant until the last known alive date. The cumulative incidence percentage of grade II-IV acute GvHD at day +100 was calculated along with a 95% confidence interval.
Outcome measures
| Measure |
Sitagliptin
n=37 Participants
Sitagliptin 600 mg q 12 hours PO starting on Day -1 before transplant to be administered between 8:00 am and 10:00 am then given every 12 hours (total 32 doses) through day +14.
Sitagliptin: 600 mg ever 12 hours by mouth will be given starting the day before transplant through day +14 after transplant
|
|---|---|
|
Percentage of Patients With Grade III-IV Acute GvHD at Day +100
|
2.7 percentage of participants
Interval 0.2 to 12.3
|
SECONDARY outcome
Timeframe: up to 1 monthPopulation: All patients who received a transplant
Time to neutrophil engraftment will be analyzed by the Kaplan-Meier method. The time to engraftment of neutrophils is defined as the time from day 0 to the date of the first of three consecutive days after transplantation during which the absolute neutrophils count (ANC) is at least 0.5 x109/l. Patients who did not have neutrophil engraftment before death will be censored at the date of death. The median and 95% confidence intervals were calculated.
Outcome measures
| Measure |
Sitagliptin
n=37 Participants
Sitagliptin 600 mg q 12 hours PO starting on Day -1 before transplant to be administered between 8:00 am and 10:00 am then given every 12 hours (total 32 doses) through day +14.
Sitagliptin: 600 mg ever 12 hours by mouth will be given starting the day before transplant through day +14 after transplant
|
|---|---|
|
Median Time to Engraftment of Neutrophils
|
13 days
Interval 12.0 to 15.0
|
SECONDARY outcome
Timeframe: up to 4 monthsPopulation: All patients who received a transplant.
Time to platelet engraftment will be analyzed by the Kaplan-Meier method. The time to engraftment of platelets is defined as the time from day 0 to the first of seven consecutive Complete Blood Counts (CBCs) obtained on different days after transplantation during which the platelet count is at least 20 x109/l. The CBCs obtained should be at least seven days after the most recent platelet transfusion. The median and 95% confidence intervals were calculated.
Outcome measures
| Measure |
Sitagliptin
n=37 Participants
Sitagliptin 600 mg q 12 hours PO starting on Day -1 before transplant to be administered between 8:00 am and 10:00 am then given every 12 hours (total 32 doses) through day +14.
Sitagliptin: 600 mg ever 12 hours by mouth will be given starting the day before transplant through day +14 after transplant
|
|---|---|
|
Median Time to Engraftment of Platelets
|
15 days
Interval 14.0 to 16.0
|
SECONDARY outcome
Timeframe: 100 days from transplantPopulation: All patients who received a transplant
Number of unique patients who had each type of infection (i.e., viral, bacterial, fungal, etc.) during the 100 days post transplant. A patient could have more than one type of infection.
Outcome measures
| Measure |
Sitagliptin
n=37 Participants
Sitagliptin 600 mg q 12 hours PO starting on Day -1 before transplant to be administered between 8:00 am and 10:00 am then given every 12 hours (total 32 doses) through day +14.
Sitagliptin: 600 mg ever 12 hours by mouth will be given starting the day before transplant through day +14 after transplant
|
|---|---|
|
Number of Unique Patients With Infections by Day +100
Bacterial
|
5 Participants
|
|
Number of Unique Patients With Infections by Day +100
Gram Positive Bacteria
|
1 Participants
|
|
Number of Unique Patients With Infections by Day +100
Other Bacteria
|
1 Participants
|
|
Number of Unique Patients With Infections by Day +100
Fungal
|
1 Participants
|
|
Number of Unique Patients With Infections by Day +100
Viral
|
11 Participants
|
|
Number of Unique Patients With Infections by Day +100
CMV
|
1 Participants
|
SECONDARY outcome
Timeframe: 1 year from transplantPopulation: All patients who received a transplant.
Kaplan-Meier methods will be used to conduct a competing risk analysis. Time until non-relapse death will be calculated from transplant until death. Patients who died from relapse will be considered a competing risk and calculated from time of transplant until death. Otherwise, patients will be censored and calculated from transplant until the last known alive date. The cumulative incidence percentage of non-relapse mortality at day +365 was calculated along with a 95% confidence interval.
Outcome measures
| Measure |
Sitagliptin
n=37 Participants
Sitagliptin 600 mg q 12 hours PO starting on Day -1 before transplant to be administered between 8:00 am and 10:00 am then given every 12 hours (total 32 doses) through day +14.
Sitagliptin: 600 mg ever 12 hours by mouth will be given starting the day before transplant through day +14 after transplant
|
|---|---|
|
Percentage of Patients With Non-relapse Mortality (NRM) at +1 Year
|
0 percentage of participants
Since no patients died from non-relapse mortality by 1 year, a confidence interval was not generated.
|
SECONDARY outcome
Timeframe: 1 year from transplantPopulation: All patients who received a transplant.
Duration of time from the start of treatment to time of death due to any causes. Patients who do not die will be censored on their last known alive date. Kaplan-Meier methods will be used and the median and 95% confidence intervals will be calculated. The cumulative incidence percentage of survival at day +365 was calculated along with a 95% confidence interval.
Outcome measures
| Measure |
Sitagliptin
n=37 Participants
Sitagliptin 600 mg q 12 hours PO starting on Day -1 before transplant to be administered between 8:00 am and 10:00 am then given every 12 hours (total 32 doses) through day +14.
Sitagliptin: 600 mg ever 12 hours by mouth will be given starting the day before transplant through day +14 after transplant
|
|---|---|
|
Percentage of Patients Surviving at +1 Year
|
94.3 percentage of participants
Interval 79.0 to 98.5
|
SECONDARY outcome
Timeframe: 1 year from transplantPopulation: Patients on study at least 100 days post-transplant
Patients surviving at least 100 days will be evaluable for chronic GvHD. The cumulative incidence of chronic GvHD (total, and mild, moderate, severe) will be described using deaths from causes other than chronic GvHD considered as a competing risk. Kaplan-Meier methods will be used to conduct a competing risk analysis. Time until chronic GvHD will be calculated from transplant until chronic GvHD or death from GvHD. Patients who relapsed or died from causes other than GvHD will be considered a competing risk and calculated from time of transplant until relapse or death. Otherwise, patients will be censored and calculated from transplant until the last known alive date. The cumulative incidence percentage at 1 year will calculated along with a 95% confidence interval.
Outcome measures
| Measure |
Sitagliptin
n=36 Participants
Sitagliptin 600 mg q 12 hours PO starting on Day -1 before transplant to be administered between 8:00 am and 10:00 am then given every 12 hours (total 32 doses) through day +14.
Sitagliptin: 600 mg ever 12 hours by mouth will be given starting the day before transplant through day +14 after transplant
|
|---|---|
|
Percentage of Patients Diagnosed With Chronic GvHD at 1 Year
|
37.4 percentage of participants
Interval 21.5 to 53.4
|
SECONDARY outcome
Timeframe: 1 year from transplantPopulation: All patients who received a transplant
Kaplan-Meier methods will be used to conduct a competing risk analysis. Time until relapse will be calculated from transplant until relapse or death from relapse. Patients who died from causes other than relapse will be considered a competing risk and calculated from time of transplant until death. Otherwise, patients will be censored and calculated from transplant until the last known alive date. The cumulative incidence percentage of relapse at day +365 was calculated along with a 95% confidence interval.
Outcome measures
| Measure |
Sitagliptin
n=37 Participants
Sitagliptin 600 mg q 12 hours PO starting on Day -1 before transplant to be administered between 8:00 am and 10:00 am then given every 12 hours (total 32 doses) through day +14.
Sitagliptin: 600 mg ever 12 hours by mouth will be given starting the day before transplant through day +14 after transplant
|
|---|---|
|
Percentage of Patients With Relapse of the Primary Hematological Malignancy at 1 Year
|
25.6 percentage of participants
Interval 12.5 to 40.9
|
Adverse Events
Sitagliptin
Serious adverse events
| Measure |
Sitagliptin
n=37 participants at risk
Sitagliptin 600 mg q 12 hours PO starting on Day -1 before transplant to be administered between 8:00 am and 10:00 am then given every 12 hours (total 32 doses) through day +14.
Sitagliptin: 600 mg ever 12 hours by mouth will be given starting the day before transplant through day +14 after transplant
|
|---|---|
|
General disorders
Multi-organ failure
|
2.7%
1/37 • Up to 2 months for Adverse Events (Serious and Other). Up to 2 years for all cause mortality.
|
|
Infections and infestations
Upper respiratory infection
|
2.7%
1/37 • Up to 2 months for Adverse Events (Serious and Other). Up to 2 years for all cause mortality.
|
|
Metabolism and nutrition disorders
Dehydration
|
2.7%
1/37 • Up to 2 months for Adverse Events (Serious and Other). Up to 2 years for all cause mortality.
|
|
Renal and urinary disorders
Acute kidney injury
|
8.1%
3/37 • Up to 2 months for Adverse Events (Serious and Other). Up to 2 years for all cause mortality.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
2.7%
1/37 • Up to 2 months for Adverse Events (Serious and Other). Up to 2 years for all cause mortality.
|
Other adverse events
| Measure |
Sitagliptin
n=37 participants at risk
Sitagliptin 600 mg q 12 hours PO starting on Day -1 before transplant to be administered between 8:00 am and 10:00 am then given every 12 hours (total 32 doses) through day +14.
Sitagliptin: 600 mg ever 12 hours by mouth will be given starting the day before transplant through day +14 after transplant
|
|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
10.8%
4/37 • Up to 2 months for Adverse Events (Serious and Other). Up to 2 years for all cause mortality.
|
|
Blood and lymphatic system disorders
Hemolysis
|
5.4%
2/37 • Up to 2 months for Adverse Events (Serious and Other). Up to 2 years for all cause mortality.
|
|
Gastrointestinal disorders
Diarrhea
|
10.8%
4/37 • Up to 2 months for Adverse Events (Serious and Other). Up to 2 years for all cause mortality.
|
|
Gastrointestinal disorders
Dysphagia
|
5.4%
2/37 • Up to 2 months for Adverse Events (Serious and Other). Up to 2 years for all cause mortality.
|
|
Gastrointestinal disorders
Mucositis oral
|
59.5%
22/37 • Up to 2 months for Adverse Events (Serious and Other). Up to 2 years for all cause mortality.
|
|
General disorders
Edema limbs
|
5.4%
2/37 • Up to 2 months for Adverse Events (Serious and Other). Up to 2 years for all cause mortality.
|
|
Infections and infestations
Bladder infection
|
5.4%
2/37 • Up to 2 months for Adverse Events (Serious and Other). Up to 2 years for all cause mortality.
|
|
Infections and infestations
Sepsis
|
5.4%
2/37 • Up to 2 months for Adverse Events (Serious and Other). Up to 2 years for all cause mortality.
|
|
Metabolism and nutrition disorders
Anorexia
|
27.0%
10/37 • Up to 2 months for Adverse Events (Serious and Other). Up to 2 years for all cause mortality.
|
|
Nervous system disorders
Headache
|
5.4%
2/37 • Up to 2 months for Adverse Events (Serious and Other). Up to 2 years for all cause mortality.
|
|
Renal and urinary disorders
Acute kidney injury
|
24.3%
9/37 • Up to 2 months for Adverse Events (Serious and Other). Up to 2 years for all cause mortality.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
5.4%
2/37 • Up to 2 months for Adverse Events (Serious and Other). Up to 2 years for all cause mortality.
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
5.4%
2/37 • Up to 2 months for Adverse Events (Serious and Other). Up to 2 years for all cause mortality.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary edema
|
5.4%
2/37 • Up to 2 months for Adverse Events (Serious and Other). Up to 2 years for all cause mortality.
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
10.8%
4/37 • Up to 2 months for Adverse Events (Serious and Other). Up to 2 years for all cause mortality.
|
|
Vascular disorders
Hypertension
|
16.2%
6/37 • Up to 2 months for Adverse Events (Serious and Other). Up to 2 years for all cause mortality.
|
|
Vascular disorders
Hypotension
|
5.4%
2/37 • Up to 2 months for Adverse Events (Serious and Other). Up to 2 years for all cause mortality.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place