<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/NCT02997280</url>
  </required_header>
  <id_info>
    <org_study_id>2016-29-1</org_study_id>
    <nct_id>NCT02997280</nct_id>
  </id_info>
  <brief_title>Ruxolitinib for Steroid-refractory GVHD</brief_title>
  <official_title>Treatment of Steroid-refractory Acute and Chronic Graft-versus-host Disease With Inhibitor of Janus Kinases</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>St. Petersburg State Pavlov Medical University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ministry of Health, Russian Federation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>St. Petersburg State Pavlov Medical University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Steroid-refractory acute GVHD (srGVHD) is one of the causes of mortality after allogeneic&#xD;
      stem cell transplantation, while steroid-refractory chronic GVHD significantly increases&#xD;
      morbidity, aggravates quality of life and may also impact survival. Currently there is no&#xD;
      standard treatment of srGVHD. One of the most promising agents is Janus kinase (JAK)&#xD;
      inhibitor ruxolitinib, which in the retrospective study demonstrated excellent response rate&#xD;
      and survival of patients with either acute or chronic srGVHD. This study prospectively&#xD;
      evaluates the efficacy of ruxolitinib in srGVHD patients.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 2016</start_date>
  <completion_date type="Actual">April 2019</completion_date>
  <primary_completion_date type="Actual">December 2018</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>Overall response rate</measure>
    <time_frame>84 days</time_frame>
    <description>Partial response for acute GVHD is defined as the improvement of at least one stage in the severity of aGVHD in one organ without deterioration in any other organ. A response had to last for at least 3 weeks. Partial response for chronic GVHD was defined as reduction in GVHD National Institute of Health (NIH) severity score at east for one organ without deterioration in any other organ. A complete response was defined as the absence of any symptoms related to GVHD. Overall response is defined as presence of partial or complete response</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>6-month overall survival</measure>
    <time_frame>6 months</time_frame>
    <description>Time from start of ruxolitinib until death or 6 months, summarized using Kaplan-Meier estimates.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Toxicity based NCI CTC grades</measure>
    <time_frame>6 months</time_frame>
    <description>Toxicity parameters based on NCI CTCAE 4.03 grades: nasea, vomiting, anemia, thrombocytopenia, leukopenia, neutropenia, hepatotoxicity (liver function tests), nephrotoxicity (creatinine), neurotoxicity (attending physician assessment), hemorrhagic cystitis (attending physician assessment).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>GVHD relapse incidence after complete response</measure>
    <time_frame>6 months</time_frame>
    <description>Time from stopping ruxolitinib until recurrence of GVHD or 6 months, summarized using cumulative incidence estimates.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relapse incidence of underlying hematologic malignancy</measure>
    <time_frame>12 months</time_frame>
    <description>Time from starting ruxolitinib until hematologic relapse or 12 months, summarized using cumulative incidence estimates</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life measured by FACT BMT ver. 4 questionnaire in adults</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life measured by PedQL Stem Cell transplant module ver.1.0 questionnaire in children</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">75</enrollment>
  <condition>Graft Vs Host Disease</condition>
  <arm_group>
    <arm_group_label>Ruxolitinib treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ruxolitinib 10 mg bid for adults and children with body weight &gt; 40 kg, 0.15 mg/kg bid for children with body weight &lt; 40 kg.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ruxolitinib Oral Tablet</intervention_name>
    <description>Dose reduction criteria for acute GVHD: grade 4 neutropenia or grade 4 thrombocytopenia related to ruxolitinib administration based on the decision of attending physician.&#xD;
Dose reduction criteria for chronic GVHD: grade 3 neutropenia, grade 3 thrombocytopenia or anemia requiring transfusion, related to ruxolitinib administration based on the decision of attending physician.&#xD;
Reduced dose schedule: 5 mg bid for adults and children with body weight &gt; 40 kg, 0.08 mg/kg bid for children with body weight &lt; 40 kg.&#xD;
Treatment discontinuation criteria: complete response; absence of response after 28 days or progressive disease after 7 days for acute GVHD; absence of response after 84 days or progressive disease after 28 days for chronic GVHD; life-threatening complications.</description>
    <arm_group_label>Ruxolitinib treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of graft-versus-host disease established based on tissue biopsy&#xD;
&#xD;
          -  Steroid-refractory acute or chronic graft-versus-host disease according to EBMT/ELN&#xD;
             criteria (T. Ruutu et al, 2014)&#xD;
&#xD;
          -  Age 1 to 70 years&#xD;
&#xD;
          -  Karnofsky index &gt;30%.&#xD;
&#xD;
          -  Ability for oral drug intake&#xD;
&#xD;
          -  Life expectancy &gt; 1 month&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Severe organ dysfunction: AST or ALT &gt;5 upper normal limits (excluding cases related&#xD;
             to liver GVHD), creatinine &gt;2 upper normal limits&#xD;
&#xD;
          -  Requirement for vasopressor support at the time of enrollment&#xD;
&#xD;
          -  Uncontrolled bacterial or fungal infection at the time of enrollment&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Somatic or psychiatric disorder making the patient (or legal guardian) unable to sign&#xD;
             informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Year</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Boris V Afanasyev, Prof</last_name>
    <role>Study Director</role>
    <affiliation>R.M.Gorbacheva Memorial Institute of Oncology, Hematology and Transplantation, Pavlov First Saint Petersburg State Medical University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>First Pavlov State Medical University of St. Petersburg</name>
      <address>
        <city>Saint-Petersburg</city>
        <zip>197089</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Russian Federation</country>
  </location_countries>
  <reference>
    <citation>Zeiser R, Burchert A, Lengerke C, Verbeek M, Maas-Bauer K, Metzelder SK, Spoerl S, Ditschkowski M, Ecsedi M, Sockel K, Ayuk F, Ajib S, de Fontbrune FS, Na IK, Penter L, Holtick U, Wolf D, Schuler E, Meyer E, Apostolova P, Bertz H, Marks R, Lubbert M, Wasch R, Scheid C, Stolzel F, Ordemann R, Bug G, Kobbe G, Negrin R, Brune M, Spyridonidis A, Schmitt-Graff A, van der Velden W, Huls G, Mielke S, Grigoleit GU, Kuball J, Flynn R, Ihorst G, Du J, Blazar BR, Arnold R, Kroger N, Passweg J, Halter J, Socie G, Beelen D, Peschel C, Neubauer A, Finke J, Duyster J, von Bubnoff N. Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multicenter survey. Leukemia. 2015 Oct;29(10):2062-8. doi: 10.1038/leu.2015.212. Epub 2015 Jul 31.</citation>
    <PMID>26228813</PMID>
  </reference>
  <verification_date>April 2019</verification_date>
  <study_first_submitted>December 14, 2016</study_first_submitted>
  <study_first_submitted_qc>December 15, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 20, 2016</study_first_posted>
  <last_update_submitted>April 3, 2019</last_update_submitted>
  <last_update_submitted_qc>April 3, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">April 5, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>St. Petersburg State Pavlov Medical University</investigator_affiliation>
    <investigator_full_name>Ivan S Moiseev</investigator_full_name>
    <investigator_title>Head of oncology, hematology and transplantation department for adults</investigator_title>
  </responsible_party>
  <keyword>acute graft-versus-host disease</keyword>
  <keyword>chronic graft-versus-host disease</keyword>
  <keyword>Steroid-refractory GVHD</keyword>
  <keyword>ruxolitinib</keyword>
  <keyword>JAK inhibitors</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Graft vs Host Disease</mesh_term>
  </condition_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/NCT02997280
org study id: 2016-29-1
nct id: NCT02997280
lead sponsor: 
collaborator: 
has dmc: No
Steroid-refractory acute GVHD (srGVHD) is one of the causes of mortality after allogeneic
      stem cell transplantation, while steroid-refractory chronic GVHD significantly increases
      morbidity, aggravates quality of life and may also impact survival. Currently there is no
      standard treatment of srGVHD. One of the most promising agents is Janus kinase (JAK)
      inhibitor ruxolitinib, which in the retrospective study demonstrated excellent response rate
      and survival of patients with either acute or chronic srGVHD. This study prospectively
      evaluates the efficacy of ruxolitinib in srGVHD patients.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall response rate
time frame: 84 days
description: Partial response for acute GVHD is defined as the improvement of at least one stage in the severity of aGVHD in one organ without deterioration in any other organ. A response had to last for at least 3 weeks. Partial response for chronic GVHD was defined as reduction in GVHD National Institute of Health (NIH) severity score at east for one organ without deterioration in any other organ. A complete response was defined as the absence of any symptoms related to GVHD. Overall response is defined as presence of partial or complete response
measure: 6-month overall survival
time frame: 6 months
description: Time from start of ruxolitinib until death or 6 months, summarized using Kaplan-Meier estimates.
measure: Toxicity based NCI CTC grades
time frame: 6 months
description: Toxicity parameters based on NCI CTCAE 4.03 grades: nasea, vomiting, anemia, thrombocytopenia, leukopenia, neutropenia, hepatotoxicity (liver function tests), nephrotoxicity (creatinine), neurotoxicity (attending physician assessment), hemorrhagic cystitis (attending physician assessment).
measure: Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence
time frame: 6 months
measure: GVHD relapse incidence after complete response
time frame: 6 months
description: Time from stopping ruxolitinib until recurrence of GVHD or 6 months, summarized using cumulative incidence estimates.
measure: Relapse incidence of underlying hematologic malignancy
time frame: 12 months
description: Time from starting ruxolitinib until hematologic relapse or 12 months, summarized using cumulative incidence estimates
measure: Quality of life measured by FACT BMT ver. 4 questionnaire in adults
time frame: 6 months
measure: Quality of life measured by PedQL Stem Cell transplant module ver.1.0 questionnaire in children
time frame: 6 months
arm group label: Ruxolitinib treatment
arm group type: Experimental
description: Ruxolitinib 10 mg bid for adults and children with body weight > 40 kg, 0.15 mg/kg bid for children with body weight < 40 kg.
intervention type: Drug
intervention name: Ruxolitinib Oral Tablet
description: Dose reduction criteria for acute GVHD: grade 4 neutropenia or grade 4 thrombocytopenia related to ruxolitinib administration based on the decision of attending physician.
Dose reduction criteria for chronic GVHD: grade 3 neutropenia, grade 3 thrombocytopenia or anemia requiring transfusion, related to ruxolitinib administration based on the decision of attending physician.
Reduced dose schedule: 5 mg bid for adults and children with body weight > 40 kg, 0.08 mg/kg bid for children with body weight < 40 kg.
Treatment discontinuation criteria: complete response; absence of response after 28 days or progressive disease after 7 days for acute GVHD; absence of response after 84 days or progressive disease after 28 days for chronic GVHD; life-threatening complications.
arm group label: Ruxolitinib treatment
criteria: 
gender: All
minimum age: 1 Year
maximum age: 70 Years
healthy volunteers: No
last name: Boris V Afanasyev, Prof
role: Study Director
affiliation: R.M.Gorbacheva Memorial Institute of Oncology, Hematology and Transplantation, Pavlov First Saint Petersburg State Medical University
facility: 
country: Russian Federation
citation: Zeiser R, Burchert A, Lengerke C, Verbeek M, Maas-Bauer K, Metzelder SK, Spoerl S, Ditschkowski M, Ecsedi M, Sockel K, Ayuk F, Ajib S, de Fontbrune FS, Na IK, Penter L, Holtick U, Wolf D, Schuler E, Meyer E, Apostolova P, Bertz H, Marks R, Lubbert M, Wasch R, Scheid C, Stolzel F, Ordemann R, Bug G, Kobbe G, Negrin R, Brune M, Spyridonidis A, Schmitt-Graff A, van der Velden W, Huls G, Mielke S, Grigoleit GU, Kuball J, Flynn R, Ihorst G, Du J, Blazar BR, Arnold R, Kroger N, Passweg J, Halter J, Socie G, Beelen D, Peschel C, Neubauer A, Finke J, Duyster J, von Bubnoff N. Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multicenter survey. Leukemia. 2015 Oct;29(10):2062-8. doi: 10.1038/leu.2015.212. Epub 2015 Jul 31.
PMID: 26228813
responsible party type: Principal Investigator
investigator affiliation: St. Petersburg State Pavlov Medical University
investigator full name: Ivan S Moiseev
investigator title: Head of oncology, hematology and transplantation department for adults
mesh term: Graft vs Host Disease
sharing ipd: No