Sitagliptin for Prevention of Acute Graft Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation
Condition: Graft vs Host Disease; Hematopoietic Stem Cell Transplantation
MeSH terms: Graft vs Host Disease
Study type: Interventional
Phase: Phase 2

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.).
    

Intervention name(s): Sitagliptin
Intervention type(s): Drug
Intervention description(s): 600 mg ever 12 hours by mouth will be given starting the day before transplant through day +14 after transplant
Intervention MeSH terms: Sitagliptin Phosphate
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Allogeneic; Sitagliptin