<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04448587</url>
  </required_header>
  <id_info>
    <org_study_id>0368-20</org_study_id>
    <nct_id>NCT04448587</nct_id>
  </id_info>
  <brief_title>Sitagliptin for the Treatment of Grade 3-4 and Refractory Acute Graft-versus-host Disease</brief_title>
  <acronym>GVHD</acronym>
  <official_title>Sitagliptin for the Treatment of Grade 3-4 and Refractory Acute Graft-versus-host Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Rabin Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Rabin Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The prognosis of severe (grade 3-4) and steroid refractory acute graft-versus-host disease&#xD;
      (GVHD) continues to be dismal. Sitagliptin given as GVHD-prophylaxis has recently been shown&#xD;
      to reduce the incidence of acute GVHD to less than 10% with an excellent safety profile.&#xD;
&#xD;
      In this single center and single arm phase 2 study we aim to explore the safety and efficacy&#xD;
      of sitagliptin in the treatment of severe and refractory acute GVHD.&#xD;
&#xD;
      Patient with new onset grade 3-4 acute GVHD will receive standard treatment consisting CNI&#xD;
      and methylprednisolone 1-2 mg/kg/day or an equivalent dose of prednisone. Patients with&#xD;
      refractory grade 2-4 acute GVHD will continue their current treatment; however&#xD;
      methylprednisolone dose will be reduced to ≤ 1 mg/kg/day or an equivalent dose of prednisone.&#xD;
&#xD;
      Oral sitagliptin will be commenced at a dose of 100 mg BID. The dose will be increased by 100&#xD;
      mg every three days up to a maximal dose of 300 mg BID. In the case of significant drug&#xD;
      related side effects or drug intolerance, the last tolerated dose will be resumed. Patients&#xD;
      responding well to lower doses of sitagliptin, will not be given higher doses of the drug.&#xD;
      Sitagliptin will be provided as long as deemed effective by the treating physician up to&#xD;
      three months.&#xD;
&#xD;
      The primary end point will be the proportion of patients achieving complete remission(CR),&#xD;
      very good partial response (VGPR) or partial response (PR) by day 28.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The prognosis of severe (grade 3-4) and steroid refractory acute GVHD continues to be dismal.&#xD;
      Sitagliptin given as GVHD-prophylaxis has recently been shown to reduce the incidence of&#xD;
      acute GVHD to less than 10% with an excellent safety profile.&#xD;
&#xD;
      In this single center and single arm phase 2 study we aim to explore the safety and efficacy&#xD;
      of sitagliptin in the treatment of severe and refractory acute GVHD.&#xD;
&#xD;
      Patient with new onset grade 3-4 acute GVHD will receive standard treatment consisting CNI&#xD;
      and methylprednisolone 1-2 mg/kg/day or an equivalent dose of prednisone. Patients with&#xD;
      refractory grade 2-4 acute GVHD will continue their current treatment; however&#xD;
      methylprednisolone dose will be reduced to ≤ 1 mg/kg/day or an equivalent dose of prednisone.&#xD;
&#xD;
      Oral sitagliptin will be commenced at a dose of 100 mg BID. The dose will be increased by 100&#xD;
      mg every three days up to a maximal dose of 300 mg BID. In the case of significant drug&#xD;
      related side effects or drug intolerance, the last tolerated dose will be resumed. Patients&#xD;
      responding well to lower doses of sitagliptin, will not be given higher doses of the drug.&#xD;
      Sitagliptin will be provided as long as deemed effective by the treating physician up to&#xD;
      three months.&#xD;
&#xD;
      The primary end point will be the proportion of patients achieving CR, VGPR or PR by day 28.&#xD;
      The secondary endpoints will be safety profile, proportion of patients achieving CR, VGPR or&#xD;
      PR by day 56, 6-month duration of response (time from first response to GVHD progression or&#xD;
      death), proportion of patients discontinuing immunosuppressive treatment by 3 and 6 months,&#xD;
      proportion of patients developing chronic GVHD (limited and extensive) by 6 months, time to&#xD;
      response, specific organ response, biomarker profile (ST2 and REG3a), Infection profile, OS&#xD;
      at 6 months, GVHD free - disease free survival at 6 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">October 1, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2021</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Response</measure>
    <time_frame>day 28</time_frame>
    <description>proportion of patients achieving complete remission (CR), very good partial response (VGPR) or partial response (PR) by day 28.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of treatment-emergent adverse events (safety and tolerability)</measure>
    <time_frame>3 months</time_frame>
    <description>Incidence of treatment-emergent adverse events (safety and tolerability)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response</measure>
    <time_frame>day 56</time_frame>
    <description>Proportion of patients achieving CR, VGPR or PR by day 56.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response</measure>
    <time_frame>6 months</time_frame>
    <description>GVHD free - disease free survival at 6 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biomarker profile</measure>
    <time_frame>By days 0, 14, 28, 42, 56, 70, 100</time_frame>
    <description>ST2 and REG3a blood levels</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">10</enrollment>
  <condition>Graft Vs Host Disease</condition>
  <arm_group>
    <arm_group_label>Sitagliptin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sitagliptin 100mg</intervention_name>
    <description>Oral sitagliptin will be commenced at a dose of 100 mg BID. The dose will be increased by 100 mg every three days up to a maximal dose of 300 mg BID. In the case of significant drug related side effects or drug intolerance, the last tolerated dose will be resumed. Patients responding well to lower doses of sitagliptin, will not be given higher doses of the drug. Sitagliptin will be provided as long as deemed effective by the treating physician up to three months.</description>
    <arm_group_label>Sitagliptin</arm_group_label>
    <other_name>JANUVIA</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 18-year old&#xD;
&#xD;
          -  Grade 3-4 acute GVHD&#xD;
&#xD;
          -  Refractory grade 2-4 acute GVHD&#xD;
&#xD;
          -  Signed informed consent.&#xD;
&#xD;
          -  Complete remission of the disease for which the patient was transplanted for.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with diabetes mellitus requiring therapy with oral hypoglycemic medications&#xD;
             or Insulin on top of sitagliptin.&#xD;
&#xD;
          -  Serious hypersensitivity reaction to sitagliptin such as angioedema or anaphylaxis.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>17 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Moshe Yeshurun, MD</last_name>
    <phone>972-52-6015543</phone>
    <email>moshey@clalit.org.il</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Liat Shragian-Alon, MD</last_name>
    <phone>972-54-2394930</phone>
    <email>LIATSHR@clalit.org.il</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Rabin Medical Center</name>
      <address>
        <city>Petach Tikva</city>
        <country>Israel</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Moshe Yeshurun, MD</last_name>
      <phone>972-52-6015543</phone>
      <email>moshey@clalit.org.il</email>
    </contact>
  </location>
  <location_countries>
    <country>Israel</country>
  </location_countries>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>June 23, 2020</study_first_submitted>
  <study_first_submitted_qc>June 25, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 26, 2020</study_first_posted>
  <last_update_submitted>January 29, 2021</last_update_submitted>
  <last_update_submitted_qc>January 29, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 2, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Rabin Medical Center</investigator_affiliation>
    <investigator_full_name>moshe yeshurun</investigator_full_name>
    <investigator_title>Head BMT Unit</investigator_title>
  </responsible_party>
  <keyword>SITAGLIPTIN</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Graft vs Host Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sitagliptin Phosphate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04448587
org study id: 0368-20
nct id: NCT04448587
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The prognosis of severe (grade 3-4) and steroid refractory acute graft-versus-host disease
      (GVHD) continues to be dismal. Sitagliptin given as GVHD-prophylaxis has recently been shown
      to reduce the incidence of acute GVHD to less than 10% with an excellent safety profile.

      In this single center and single arm phase 2 study we aim to explore the safety and efficacy
      of sitagliptin in the treatment of severe and refractory acute GVHD.

      Patient with new onset grade 3-4 acute GVHD will receive standard treatment consisting CNI
      and methylprednisolone 1-2 mg/kg/day or an equivalent dose of prednisone. Patients with
      refractory grade 2-4 acute GVHD will continue their current treatment; however
      methylprednisolone dose will be reduced to ≤ 1 mg/kg/day or an equivalent dose of prednisone.

      Oral sitagliptin will be commenced at a dose of 100 mg BID. The dose will be increased by 100
      mg every three days up to a maximal dose of 300 mg BID. In the case of significant drug
      related side effects or drug intolerance, the last tolerated dose will be resumed. Patients
      responding well to lower doses of sitagliptin, will not be given higher doses of the drug.
      Sitagliptin will be provided as long as deemed effective by the treating physician up to
      three months.

      The primary end point will be the proportion of patients achieving complete remission(CR),
      very good partial response (VGPR) or partial response (PR) by day 28.
The prognosis of severe (grade 3-4) and steroid refractory acute GVHD continues to be dismal.
      Sitagliptin given as GVHD-prophylaxis has recently been shown to reduce the incidence of
      acute GVHD to less than 10% with an excellent safety profile.

      In this single center and single arm phase 2 study we aim to explore the safety and efficacy
      of sitagliptin in the treatment of severe and refractory acute GVHD.

      Patient with new onset grade 3-4 acute GVHD will receive standard treatment consisting CNI
      and methylprednisolone 1-2 mg/kg/day or an equivalent dose of prednisone. Patients with
      refractory grade 2-4 acute GVHD will continue their current treatment; however
      methylprednisolone dose will be reduced to ≤ 1 mg/kg/day or an equivalent dose of prednisone.

      Oral sitagliptin will be commenced at a dose of 100 mg BID. The dose will be increased by 100
      mg every three days up to a maximal dose of 300 mg BID. In the case of significant drug
      related side effects or drug intolerance, the last tolerated dose will be resumed. Patients
      responding well to lower doses of sitagliptin, will not be given higher doses of the drug.
      Sitagliptin will be provided as long as deemed effective by the treating physician up to
      three months.

      The primary end point will be the proportion of patients achieving CR, VGPR or PR by day 28.
      The secondary endpoints will be safety profile, proportion of patients achieving CR, VGPR or
      PR by day 56, 6-month duration of response (time from first response to GVHD progression or
      death), proportion of patients discontinuing immunosuppressive treatment by 3 and 6 months,
      proportion of patients developing chronic GVHD (limited and extensive) by 6 months, time to
      response, specific organ response, biomarker profile (ST2 and REG3a), Infection profile, OS
      at 6 months, GVHD free - disease free survival at 6 months.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Response
time frame: day 28
description: proportion of patients achieving complete remission (CR), very good partial response (VGPR) or partial response (PR) by day 28.
measure: Incidence of treatment-emergent adverse events (safety and tolerability)
time frame: 3 months
description: Incidence of treatment-emergent adverse events (safety and tolerability)
measure: Response
time frame: day 56
description: Proportion of patients achieving CR, VGPR or PR by day 56.
measure: Response
time frame: 6 months
description: GVHD free - disease free survival at 6 months
measure: Biomarker profile
time frame: By days 0, 14, 28, 42, 56, 70, 100
description: ST2 and REG3a blood levels
arm group label: Sitagliptin
arm group type: Experimental
intervention type: Drug
intervention name: Sitagliptin 100mg
description: Oral sitagliptin will be commenced at a dose of 100 mg BID. The dose will be increased by 100 mg every three days up to a maximal dose of 300 mg BID. In the case of significant drug related side effects or drug intolerance, the last tolerated dose will be resumed. Patients responding well to lower doses of sitagliptin, will not be given higher doses of the drug. Sitagliptin will be provided as long as deemed effective by the treating physician up to three months.
arm group label: Sitagliptin
other name: JANUVIA
criteria: 
gender: All
minimum age: 17 Years
maximum age: 80 Years
healthy volunteers: No
last name: Moshe Yeshurun, MD
phone: 972-52-6015543
email: moshey@clalit.org.il
last name: Liat Shragian-Alon, MD
phone: 972-54-2394930
email: LIATSHR@clalit.org.il
facility: 
status: Recruiting
contact: 
country: Israel
responsible party type: Principal Investigator
investigator affiliation: Rabin Medical Center
investigator full name: moshe yeshurun
investigator title: Head BMT Unit
mesh term: Graft vs Host Disease
mesh term: Sitagliptin Phosphate
sharing ipd: No