<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/NCT03292263</url>
  </required_header>
  <id_info>
    <org_study_id>11/17-n</org_study_id>
    <nct_id>NCT03292263</nct_id>
  </id_info>
  <brief_title>ASCT With Nivolumab in Patients With Multiple Myeloma</brief_title>
  <official_title>Autologous Stem Cell Transplantation With Nivolumab in Patients With Multiple Myeloma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>St. Petersburg State Pavlov Medical University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>St. Petersburg State Pavlov Medical University</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>
      This is an open-label, single center trial of Autologous Stem Cell Transplantation (ASCT)&#xD;
      with nivolumab in multiple myeloma patients to determine the efficacy and safety of ASCT and&#xD;
      PD1 inhibitor combination.&#xD;
&#xD;
      For this purpose, 30 multiple myeloma patients, who have received induction therapy and have&#xD;
      achieved a partial response (PR), stable disease (SD) or progression, and thus have&#xD;
      unfavorable prognosis, will be treated with nivolumab administered iv at a dose of 100 mg on&#xD;
      days 3 before and 17 after high-dose melphalan with autologous stem cell transplantation.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 24, 2017</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">December 2022</primary_completion_date>
  <phase>Phase 1/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</measure>
    <time_frame>3 months</time_frame>
    <description>Includes complete response, very good partial response, and partial response (based on IMWG criteria)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (PFS)</measure>
    <time_frame>12 months</time_frame>
    <description>PFS will be assessed with Kaplan-Meier method from the date of ASCT, with day 0 defined as date of stem cell infusion (in case of tandem transplant the 2nd of 2 transplants will be used) until the date of progression, defined as the date at which the patient starts the next line of therapy or the date of death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>24 months</time_frame>
    <description>Will be assessed with Kaplan-Meier method from the date of ASCT, with day 0 defined as date of stem cell infusion (in case of tandem transplant the 2nd of 2 transplants will be used)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of grade 3 or higher treatment-related adverse events by CTCAE 4.03</measure>
    <time_frame>12 months</time_frame>
    <description>Toxicity parameters based on NCI CTCAE 4.03 grades: hematological toxicity (CBC), hepatotoxicity (liver function tests), nephrotoxicity (creatinine), neurotoxicity (attending physician assessment), fatigue (attending physician assessment), rash (attending physician assessment), colitis (attending physician assessment), pneumonitis (attending physician assessment), autoimmune disorders (level of hormones, presence of autoimmune antibodies, attending physician assessment).</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>Mel+Nivo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Autologous Stem Cell Transplant Drug: Melphalan 140-200 mg/m^2, Nivolumab100 mg iv days -3, +17</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Melphalan</intervention_name>
    <description>iv infusion 70-100 mg/m2 on day -3, -2</description>
    <arm_group_label>Mel+Nivo</arm_group_label>
    <other_name>Alkeran</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nivolumab</intervention_name>
    <description>iv infusion 100 mg on day -3, +17</description>
    <arm_group_label>Mel+Nivo</arm_group_label>
    <other_name>Opdivo</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Autologous Stem Cell Transplantation</intervention_name>
    <description>peripheral blood stem cell transfusion at day 0</description>
    <arm_group_label>Mel+Nivo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects with MM (Multiple Myeloma)&#xD;
&#xD;
          -  Partial response, stable disease or progression after induction therapy (including&#xD;
             ASCT)&#xD;
&#xD;
          -  Measurable disease&#xD;
&#xD;
          -  Successful peripheral blood stem cell collection with G-CSF&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
          -  Patients after first-line induction therapy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Another malignancy requiring treatment at the time of inclusion&#xD;
&#xD;
          -  History of interstitial lung disease or pneumonitis&#xD;
&#xD;
          -  Patients with any other known concurrent severe and/or uncontrolled medical condition&#xD;
             (e.g. uncontrolled diabetes; cardiovascular disease including congestive heart failure&#xD;
             NYHA Class III or IV, myocardial infarction within 6 months, and poorly controlled&#xD;
             hypertension) which, in the opinion of the investigator could compromise participation&#xD;
             in the study&#xD;
&#xD;
          -  Uncontrolled bacterial or fungal infection at the time of enrollment&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Somatic or psychiatric disorder making the patient unable to sign informed consent&#xD;
&#xD;
          -  Active or prior documented autoimmune disease requiring systemic treatment&#xD;
&#xD;
          -  Prior treatment with anti-PD-1, anti-PD-L1, or anti-CTLA4 therapy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Boris V Afanasyev, MD, Prof.</last_name>
    <phone>+78123386265</phone>
    <email>coordinatorbmt@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Ivan S Moiseev, MD, PhD</last_name>
    <phone>+79217961951</phone>
    <email>moisiv@mail.ru</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Boris V Afanasyev, MD, Prof.</name>
      <address>
        <city>Saint Petersburg</city>
        <zip>197089</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Olga V Pirogova, PhD</last_name>
      <phone>+79214419016</phone>
      <email>dr.pirogova@gmail.com</email>
    </contact>
    <contact_backup>
      <last_name>Ivan S Moiseev, PhD</last_name>
      <phone>+79217961951</phone>
      <email>moisiv@mail.ru</email>
    </contact_backup>
    <investigator>
      <last_name>Kirill V Lepik, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Russian Federation</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>September 21, 2017</study_first_submitted>
  <study_first_submitted_qc>September 22, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 25, 2017</study_first_posted>
  <last_update_submitted>April 4, 2022</last_update_submitted>
  <last_update_submitted_qc>April 4, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 5, 2022</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>R.M.Gorbacheva memorial institute vice director for research</investigator_title>
  </responsible_party>
  <keyword>Multiple Myeloma</keyword>
  <keyword>Nivolumab</keyword>
  <keyword>Melphalan</keyword>
  <keyword>Autologous hematopoietic stem cell transplantation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Myeloma</mesh_term>
    <mesh_term>Neoplasms, Plasma Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nivolumab</mesh_term>
    <mesh_term>Melphalan</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03292263
org study id: 11/17-n
nct id: NCT03292263
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is an open-label, single center trial of Autologous Stem Cell Transplantation (ASCT)
      with nivolumab in multiple myeloma patients to determine the efficacy and safety of ASCT and
      PD1 inhibitor combination.

      For this purpose, 30 multiple myeloma patients, who have received induction therapy and have
      achieved a partial response (PR), stable disease (SD) or progression, and thus have
      unfavorable prognosis, will be treated with nivolumab administered iv at a dose of 100 mg on
      days 3 before and 17 after high-dose melphalan with autologous stem cell transplantation.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall response
time frame: 3 months
description: Includes complete response, very good partial response, and partial response (based on IMWG criteria)
measure: Progression free survival (PFS)
time frame: 12 months
description: PFS will be assessed with Kaplan-Meier method from the date of ASCT, with day 0 defined as date of stem cell infusion (in case of tandem transplant the 2nd of 2 transplants will be used) until the date of progression, defined as the date at which the patient starts the next line of therapy or the date of death.
measure: Overall Survival (OS)
time frame: 24 months
description: Will be assessed with Kaplan-Meier method from the date of ASCT, with day 0 defined as date of stem cell infusion (in case of tandem transplant the 2nd of 2 transplants will be used)
measure: Frequency of grade 3 or higher treatment-related adverse events by CTCAE 4.03
time frame: 12 months
description: Toxicity parameters based on NCI CTCAE 4.03 grades: hematological toxicity (CBC), hepatotoxicity (liver function tests), nephrotoxicity (creatinine), neurotoxicity (attending physician assessment), fatigue (attending physician assessment), rash (attending physician assessment), colitis (attending physician assessment), pneumonitis (attending physician assessment), autoimmune disorders (level of hormones, presence of autoimmune antibodies, attending physician assessment).
arm group label: Mel+Nivo
arm group type: Experimental
description: Autologous Stem Cell Transplant Drug: Melphalan 140-200 mg/m^2, Nivolumab100 mg iv days -3, +17
intervention type: Drug
intervention name: Melphalan
description: iv infusion 70-100 mg/m2 on day -3, -2
arm group label: Mel+Nivo
other name: Alkeran
intervention type: Drug
intervention name: Nivolumab
description: iv infusion 100 mg on day -3, +17
arm group label: Mel+Nivo
other name: Opdivo
intervention type: Procedure
intervention name: Autologous Stem Cell Transplantation
description: peripheral blood stem cell transfusion at day 0
arm group label: Mel+Nivo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Boris V Afanasyev, MD, Prof.
phone: +78123386265
email: coordinatorbmt@gmail.com
last name: Ivan S Moiseev, MD, PhD
phone: +79217961951
email: moisiv@mail.ru
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: Russian Federation
responsible party type: Principal Investigator
investigator affiliation: St. Petersburg State Pavlov Medical University
investigator full name: Ivan S Moiseev
investigator title: R.M.Gorbacheva memorial institute vice director for research
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Nivolumab
mesh term: Melphalan
sharing ipd: Undecided