Back to resultsSitagliptin for Prevention of aGVHD After Alternative Donor Transplantation
Primary Purpose
Acute-graft-versus-host Disease, Allogeneic Hematopoietic Stem Cell Transplantation
Status
Recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Sitagliptin + Standard Prophylaxis
Standard Prophylaxis
Sponsored by
About this trial
This is an interventional prevention trial for Acute-graft-versus-host Disease focused on measuring Sitagliptin, Alternative Donor
Eligibility Criteria
Inclusion Criteria:
- Patient age ≥ 18 to ≤ 60 years
- ECOG score 0-2 points/Karnofsky score ≧80
- To receive allogeneic hematopoietic stem cell transplantation from related haploid or unrelated donor
- The pretreatment of modified Bu/Cy+ATG scheme was planned.
- Patients with malignant hematological diseases indicated by transplantation and in CR state
- Expected survival ≥ 3 months
- Signed written informed consent (Patient must be capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent)
- Agree to use effective contraception
Exclusion Criteria:
- Prior allogeneic hematopoietic stem cell transplant
- Allergy/intolerance to Sitagliptin
- There are contraindications for Sitagliptin use.
- Moderate or severe renal insufficiency
- Patients with diabetes mellitus requiring insulin secretagogues and/or insulin
- Human immunodeficiency virus or active hepatitis C virus or active hepatitis B virus infection
- Active infection that is difficult to control
- Vital organ function cannot tolerate transplantation
- Other malignant tumors outside the blood system, except the following diseases: malignant tumors that have been cured for 3 years without active lesions; Adequate treatment of non-melanoma skin cancer without active foci of malignant amygdala and carcinoma in situ
- There is evidence that may interfere with the study or make patients at risk of serious complications or medical conditions, including but not limited to serious cardiovascular diseases (such as New York heart association class III or IV heart disease over the past six months of myocardial infarction, unstable type of cardiac arrhythmias) or unstable angina and/or severe lung disease (e.g. History of severe obstructive pulmonary disease and symptomatic bronchospasm)
- Pregnant or lactating women
- Any life-threatening medical condition or organ system dysfunction considered by the investigator may endanger the patient's safety by interfering with the absorption or metabolism of sitagliptin or putting study results at unnecessary risk
Sites / Locations
- The First Affiliated Hospital of Soochow University, Jiangsu Institute of HematologyRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Sitagliptin Group
Standard Group
Arm Description
95 adult patients with hematologic malignancies receiving Alternative Donor HSCT, who will receive Sitagliptin combined with Standard prophylaxis regimen for GVHD of Alternative Donor HSCT.
95 adult patients with hematologic malignancies receiving Alternative Donor HSCT, who will only receive Standard prophylaxis regimen for GVHD of Alternative Donor HSCT
Outcomes
Primary Outcome Measures
Development Grade II-IV Acute GVHD by Day +100 Following Transplantation
Percent of patients and the 95% Confidence interval who have Grade II-IV Acute GVHD by 100 days following transplantation. Only patients who were on the study for at least 100 days post transplantation were included in the analysis.
Secondary Outcome Measures
Development Grade II-IV Acute GVHD at Day +100
Fine-Gray and Cause-specific COX methods will be used to conduct a competing risk analysis. Time until grade II-IV acute GVHD will be calculated from transplant through 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 population 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.
Percentage of Patients With Grade III-IV Acute GVHD at Day +100
Fine-Gray and Cause-specific COX 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.
Cumulative incidence of early transplant-related death (TRM) within 100 days after transplantation
Percent of patients and the 95% Confidence interval who died within 100 days after transplantation.
Median Time to Engraftment of Neutrophils
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.
Median Time to Engraftment of Platelets
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.
Number of Unique Patients With Infections by Day +100
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.
Percentage of Patients With Non-relapse Mortality (NRM) at +1 Year
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.
Percentage of Patients Surviving at +1 Year
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.
Percentage of Patients Diagnosed With Chronic GVHD at 1 Year
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.
Percentage of Patients With Relapse of the Primary Hematological Malignancy at 1 Year
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.
Full Information
NCT ID
NCT05149365
First Posted
November 25, 2021
Last Updated
March 28, 2023
Sponsor
The First Affiliated Hospital of Soochow University
Collaborators
The First Affiliated Hospital with Nanjing Medical University, The Second People's Hospital of Huai'an, The First People's Hospital of Changzhou, Xinqiao Hospital of Chongqing, Shenzhen People's Hospital
1. Study Identification
Unique Protocol Identification Number
NCT05149365
Brief Title
Sitagliptin for Prevention of aGVHD After Alternative Donor Transplantation
Official Title
Sitagliptin Efficacy and Safety for Prevention of Acute Graft Versus Host Disease in Patients Receiving Alternative Donor Allogeneic Hematopoietic Stem Cell Transplantation
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 22, 2021 (Actual)
Primary Completion Date
May 2023 (Anticipated)
Study Completion Date
February 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The First Affiliated Hospital of Soochow University
Collaborators
The First Affiliated Hospital with Nanjing Medical University, The Second People's Hospital of Huai'an, The First People's Hospital of Changzhou, Xinqiao Hospital of Chongqing, Shenzhen People's Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
Primary Objective:
It is hypothesized that the efficacy of Sitagliptin would reduce the incidence of grade II-IV acute Graft Versus Host Disease (GVHD) by day +100 post-transplant in patients undergoing alternative donor (related haploid or unrelated donor ) allogeneic Hematopoietic Stem Cell Transplantation (HSCT) and receiving standard GVHD prophylaxis.
Secondary Objectives
The following descriptive secondary objectives will be studied:
Determine the tolerability and potential toxicity of sitagliptin in patients undergoing allogeneic HSCT.
Determine the cumulative incidence of grades II-IV acute GVHD by day +100.
To investigate the cumulative incidence of grades III-IV acute GVHD.
To investigate the engraftment kinetics of absolute neutrophil count and platelets.
To evaluate the incidence of Cytomegalovirus (CMV), Epstein-Barr virus (EBV) and other infections occurring during the 100 days post-transplant.
To study non-relapse mortality (NRM) at day +100, and 1 year post-transplant.
Determine the overall survival at 1 year post-transplant.
Determine the incidence of chronic GVHD.
Determine the cumulative incidence of relapse of the primary hematological malignancy.
Detailed Description
This is a Prospective, Multi-center, Open-label, Randomized, Controlled clinical trial of Sitagliptin for the prevention and safety of aGVHD after Alternative Donor hematopoietic stem cell transplantation.
190 adult patients with hematologic malignancies receiving haploid or unrelated donor sourced HSCT are planned to be enrolled competitively in this study from 5 clinical centers in China. These patients will be randomly assigned to two groups of 95 patients each, which one is experimental group and the other is control group. 95 patients in experimental group will receive Sitagliptin combined with Standard prophylaxis for GVHD. 95 patients in the control group will receive Standard prophylaxis regimen for GVHD of Alternative Donor HSCT.
Control group uses antithymocyte immunoglobulin (ATG)+cyclosporin A (CSA)+MMF+MTX for GVHD prophylaxis with the details as follows: CSA 3mg/kg continuous i.v. drip, start before Day -7, change to p.o. when gastrointestinal function recovers with a dose of 5mg/kg as two divided doses, maintaining CSA within 150-250ng/ml（If CsA cannot be tolerated, tacrolimus may be used as an alternative.）; MTX 15mg/m2,Day +1, 10mg/m2,Days +3, +6, and +11; MMF 0.5g bid, starting from Day -7 to day +30 for one month; ATG 2.5mg/kg/d, Day -4 to Day -1.
Experimental group will take Sitagliptin orally from d-1 to d+14 in addition to Standard Prophylaxis Regimen.
With regard to the content of dose reduction of CSA (including time and reduction rate), it is recommended for patients with hematologic malignancies in standard risk group to start to reduce dose after 3-6 months in the absence of GVHD and reoccurrence. The specific reduction rate can be determined at each site; the patients with GVHD will be managed by routine practice in this site.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute-graft-versus-host Disease, Allogeneic Hematopoietic Stem Cell Transplantation
Keywords
Sitagliptin, Alternative Donor
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Prospective, Multi-center, Open-label, Randomized, Controlled Clinical Trial
Masking
None (Open Label)
Allocation
Randomized
Enrollment
190 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Sitagliptin Group
Arm Type
Experimental
Arm Description
95 adult patients with hematologic malignancies receiving Alternative Donor HSCT, who will receive Sitagliptin combined with Standard prophylaxis regimen for GVHD of Alternative Donor HSCT.
Arm Title
Standard Group
Arm Type
Active Comparator
Arm Description
95 adult patients with hematologic malignancies receiving Alternative Donor HSCT, who will only receive Standard prophylaxis regimen for GVHD of Alternative Donor HSCT
Intervention Type
Drug
Intervention Name(s)
Sitagliptin + Standard Prophylaxis
Other Intervention Name(s)
Cyclosporine (CsA),Methotrexate (MTX), Mycopherol ester (MMF) and Antithymic Globulin
Intervention Description
Sitagliptin 600 mg ever 12 hours orally will be given starting from the day before transplantation through day +14 after transplantation and Standard prophylaxis regimen
Intervention Type
Drug
Intervention Name(s)
Standard Prophylaxis
Other Intervention Name(s)
Cyclosporine (CsA),Methotrexate (MTX), Mycopherol ester (MMF) and Antithymic Globulin
Intervention Description
Standard prophylaxis regimen for GVHD of Alternative Donor HSCT, include Cyclosporine (CsA),Methotrexate (MTX), Mycopherol ester (MMF) and Antithymic Globulin
Primary Outcome Measure Information:
Title
Development Grade II-IV Acute GVHD by Day +100 Following Transplantation
Description
Percent of patients and the 95% Confidence interval who have Grade II-IV Acute GVHD by 100 days following transplantation. Only patients who were on the study for at least 100 days post transplantation were included in the analysis.
Time Frame
up to 100 days
Secondary Outcome Measure Information:
Title
Development Grade II-IV Acute GVHD at Day +100
Description
Fine-Gray and Cause-specific COX methods will be used to conduct a competing risk analysis. Time until grade II-IV acute GVHD will be calculated from transplant through 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 population 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.
Time Frame
100 days from transplant
Title
Percentage of Patients With Grade III-IV Acute GVHD at Day +100
Description
Fine-Gray and Cause-specific COX 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.
Time Frame
100 days from transplant
Title
Cumulative incidence of early transplant-related death (TRM) within 100 days after transplantation
Description
Percent of patients and the 95% Confidence interval who died within 100 days after transplantation.
Time Frame
100 days from transplant
Title
Median Time to Engraftment of Neutrophils
Description
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.
Time Frame
up to 1 month
Title
Median Time to Engraftment of Platelets
Description
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.
Time Frame
up to 4 months
Title
Number of Unique Patients With Infections by Day +100
Description
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.
Time Frame
100 days from transplant
Title
Percentage of Patients With Non-relapse Mortality (NRM) at +1 Year
Description
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.
Time Frame
1 year from transplant
Title
Percentage of Patients Surviving at +1 Year
Description
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.
Time Frame
1 year from transplant
Title
Percentage of Patients Diagnosed With Chronic GVHD at 1 Year
Description
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.
Time Frame
1 year from transplant
Title
Percentage of Patients With Relapse of the Primary Hematological Malignancy at 1 Year
Description
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.
Time Frame
1 year from transplant
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patient age ≥ 18 to ≤ 60 years
Eastern Cooperative Oncology Group (ECOG）score 0-2 points / Karnofsky score ≧80
To receive allogeneic hematopoietic stem cell transplantation from related haploid or unrelated donor
The pretreatment of modified Bu/Cy+ATG scheme was planned.
Patients with malignant hematological diseases indicated by transplantation and in complete remission (CR) state.
Expected survival ≥ 3 months
Signed written informed consent (Patient must be capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent)
Agree to use effective contraception
Exclusion Criteria:
Prior allogeneic hematopoietic stem cell transplant
Allergy/intolerance to Sitagliptin
There are contraindications for Sitagliptin use.
Moderate or severe renal insufficiency
Patients with diabetes mellitus requiring insulin secretagogues and/or insulin
Human immunodeficiency virus or active hepatitis C virus or active hepatitis B virus infection
Active infection that is difficult to control
Vital organ function cannot tolerate transplantation
Other malignant tumors outside the blood system, except the following diseases: malignant tumors that have been cured for 3 years without active lesions; Adequate treatment of non-melanoma skin cancer without active foci of malignant amygdala and carcinoma in situ
There is evidence that may interfere with the study or make patients at risk of serious complications or medical conditions, including but not limited to serious cardiovascular diseases (such as New York heart association class III or IV heart disease over the past six months of myocardial infarction, unstable type of cardiac arrhythmias) or unstable angina and/or severe lung disease (e.g. History of severe obstructive pulmonary disease and symptomatic bronchospasm)
Pregnant or lactating women
Any life-threatening medical condition or organ system dysfunction considered by the investigator may endanger the patient's safety by interfering with the absorption or metabolism of sitagliptin or putting study results at unnecessary risk
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Suning Chen, Professor
Phone
8613814881746
Email
chensuning@sina.com
First Name & Middle Initial & Last Name or Official Title & Degree
Man Qiao
Phone
8613706208979
Email
qman_1@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Suning Chen, Professor
Organizational Affiliation
The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology
Official's Role
Principal Investigator
Facility Information:
Facility Name
The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology
City
Suzhou
State/Province
Jiangsu
ZIP/Postal Code
215000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Suning Chen
Phone
13814881746
Email
chensuning@sina.com
12. IPD Sharing Statement
Learn more about this trial
Sitagliptin for Prevention of aGVHD After Alternative Donor Transplantation
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