NCT02683525

Sitagliptin for Prevention of Acute Graft Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation

Phase II Trial of Inhibition of Dipeptidyl Peptidase (DPP)-4 With Sitagliptin for the Prevention of Acute Graft Versus-Host Disease Following Allogeneic Hematopoietic Stem Cell Transplantation

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 37 (actual)
• Sponsor: Sherif S. Farag · Academic / Other
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Not accepted

Summary

Primary Objective Evaluate the efficacy of sitagliptin in reducing the incidence of grade II-IV acute Graft Versus-Host Disease (GvHD) by day +100 post-transplant in patients undergoing allogeneic hematopoietic stem cell transplantation and receiving standard sirolimus and tacrolimus GvHD prophylaxis. Secondary Objectives The following descriptive secondary objectives will be studied: 1. Describe the tolerability and potential toxicity of sitagliptin. 2. Describe the cumulative incidence of grades II-IV acute GvHD by day +100. 3. Describe the cumulative incidence of grades III-IV acute GvHD. 4. Describe the engraftment kinetics of absolute neutrophil count and platelets. 5. Describe the incidence of infections occurring during the 100 days post-transplant. 6. Describe non-relapse mortality (NRM) at day +30, +100, and 1 year post-transplant. 7. Describe overall survival. 8. Describe the incidence of chronic GvHD. 9. Describe the cumulative incidence of relapse of the primary hematological malignancy.

Detailed description

This is an open label phase II study in patients undergoing allogeneic hematopoietic stem cell transplantation and receiving standard sirolimus and tacrolimus GvHD prophylaxis. Although the myeloablative preparative regimen is not prescribed, it is anticipated that most patients will receive total body irradiation (TBI) plus etoposide (TBI/VP16), or high-dose thiotepa plus cyclophosphamide according to institutional standards. Regardless of the preparative regimen, all patients will receive the following regimen for GvHD prophylaxis, which includes the study drug sitagliptin: Day -3: Tacrolimus is initiated on day -3 with a suggested starting dose of 0.01 mg/kg/day IV as a continuous infusion and them modified to target a serum level of 5-10 ng/ml. Serum levels should be monitored at least twice weekly until discharge, then at times of outpatient clinic visits according to institutional practice. Tacrolimus may be switched to PO dosing when the patient is able to tolerate oral intake satisfactorily. Note that concurrent use of agents such as itraconazole, voriconazole or fluconazole (at doses \> 200 mg) may inhibit the metabolism of tacrolimus, and thus increase tacrolimus levels. Initial dosing may be decreased in order to account for increased levels related to use of 'azole' agents. In addition, it is recommended to check tacrolimus levels twice weekly when these agents are initiated concurrently. Sirolimus is started on day -3 with a suggested loading dose of 1 mg PO, then 0.5 mg/day PO single dose from day -2 to maintain a target serum level of 5-10 ng/ml. Serum levels should be monitored twice weekly until discharge, then at times of outpatient clinic visits according to institutional practice. Initial dosing may be decreased in order to account for increased levels related to use of 'azole' agents. Day -1: Sitagliptin 600 mg q 12 hours PO starting on Day -1 to be administered between 8:00 am and 10:00 am then given every 12 hours (total 32 doses) through day +14. In the absence of acute GvHD, begin tapering of both tacrolimus and sirolimus on Day +100 as tolerated with a goal of stopping by Day +180. The rate of taper may be adjusted for presence of signs and symptoms of GvHD. Mycophenolate mofetil may be substituted for tacrolimus or sirolimus if any toxicity related to these drugs arises (e.g., renal failure, hemolytic microangiopathy, allergic rash, etc.).

Conditions

• Graft vs Host Disease
• Hematopoietic Stem Cell Transplantation

Interventions

Type	Name	Description
DRUG	Sitagliptin	600 mg ever 12 hours by mouth will be given starting the day before transplant through day +14 after transplant

Timeline

• Start date: 2016-02-03
• Primary completion: 2019-02-13
• Completion: 2019-10-01
• First posted: 2016-02-17
• Last updated: 2021-01-22
• Results posted: 2020-12-29

Locations

2 sites across 1 country: United States