<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/NCT01665014</url>
  </required_header>
  <id_info>
    <org_study_id>TMI MM1</org_study_id>
    <nct_id>NCT01665014</nct_id>
  </id_info>
  <brief_title>Total Marrow Irradiation and High-dose Melphalan for Double Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma</brief_title>
  <official_title>Efficacy and Safety of Double Autologous Hematopoietic Stem Cell Transplantation With Sequential Use of Total Marrow Irradiation and High-dose Melphalan in Multiple Myeloma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate if the use total marrow irradiation (TMI) as a sole&#xD;
      preparation for the first autologous hematopoietic stem cell transplantation (autoHSCT)&#xD;
      followed by high-dose melphalan used prior to second autoHSCT is safe and effective in&#xD;
      patients with multiple myeloma (MM).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      AutoHSCT is a standard treatment of patients with MM. According to soem clinical evidence&#xD;
      double autoHSCT provides survival advantage compared to a single procedure. Most frequently&#xD;
      used conditioning regimen consists pf high doses of melphalan (HD-MEL). In some studies it&#xD;
      was used in combination with total body irradiation (TBI), which, however was associated with&#xD;
      significant toxicity. In our center the standard procedure includes TBI as a single treatment&#xD;
      at 1st autoHSCT and HD-Mel at 2nd autoHSCT.&#xD;
&#xD;
      As in MM malignant plasma cells are localized almost exclusively in bone marrow there is&#xD;
      rationale to limit irradiation to bones. For this purpose in the current study we substitute&#xD;
      TBI with TMI. Additional boosts are provided for active sites of disease based on PET/CT&#xD;
      imaging. Our intention is to minimize toxicity while maintaining the treatment efficacy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date>August 2012</start_date>
  <completion_date type="Anticipated">August 2016</completion_date>
  <primary_completion_date type="Anticipated">December 2015</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>Progression-free survival</measure>
    <time_frame>three years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Rate of complete and very good partial responses</measure>
    <time_frame>six months</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Rate of severe adverse events</measure>
    <time_frame>one year</time_frame>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>Total marrow irradiation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Double autologous hematopoietic stem cell transplantation using TMI and HD-Mel</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Total marrow irradiation</intervention_name>
    <description>Mobilization of stem cells with the use of cytarabine 1.6 g/m2 followed by filgrastim 480 ug/d. Conditioning for the 1st autoHSCT: total marrow irradiation 4 Gy on days -3,-2,-1 (total 12 Gy). Conditioning for 2nd autoHSCT performed 3-4 months after the 1st one: melphalan 100 mg/m2 on days -2,-3 (total 200 mg/m2)</description>
    <arm_group_label>Total marrow irradiation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18-65 years&#xD;
&#xD;
          -  Diagnosis of multiple myeloma&#xD;
&#xD;
          -  PR, VGPR or CR at inclusion&#xD;
&#xD;
          -  Performance status WHO 0-1&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Organ dysfunction: elevated ALT, AST, bilirubin, AF; creatinine &gt;1.5 upper normal&#xD;
             limit; LVEF &lt;45%&#xD;
&#xD;
          -  Active infection&#xD;
&#xD;
          -  Unstable diabetes&#xD;
&#xD;
          -  Psychiatric diseases&#xD;
&#xD;
          -  History of high-dose chemotherapy or irradiation&#xD;
&#xD;
          -  Second malignancy&#xD;
&#xD;
          -  Pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sebastian Giebel, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Sebastian Giebel, MD</last_name>
    <phone>0048322788523</phone>
    <email>sgiebel@io.gliwice.pl</email>
  </overall_contact>
  <location>
    <facility>
      <name>Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch</name>
      <address>
        <city>Gliwice</city>
        <zip>44-101</zip>
        <country>Poland</country>
      </address>
    </facility>
    <contact>
      <last_name>Sebastian Giebel, MD</last_name>
      <phone>0048322788523</phone>
      <email>sgiebel@io.gliwice.pl</email>
    </contact>
    <investigator>
      <last_name>Sebastian Giebel, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Poland</country>
  </location_countries>
  <reference>
    <citation>Somlo G, Spielberger R, Frankel P, Karanes C, Krishnan A, Parker P, Popplewell L, Sahebi F, Kogut N, Snyder D, Liu A, Schultheiss T, Forman S, Wong JY. Total marrow irradiation: a new ablative regimen as part of tandem autologous stem cell transplantation for patients with multiple myeloma. Clin Cancer Res. 2011 Jan 1;17(1):174-82. doi: 10.1158/1078-0432.CCR-10-1912. Epub 2010 Nov 3.</citation>
    <PMID>21047977</PMID>
  </reference>
  <verification_date>August 2012</verification_date>
  <study_first_submitted>August 11, 2012</study_first_submitted>
  <study_first_submitted_qc>August 14, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 15, 2012</study_first_posted>
  <last_update_submitted>August 16, 2012</last_update_submitted>
  <last_update_submitted_qc>August 16, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 17, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>autologous hematopoietic stem cell transplantation</keyword>
  <keyword>total marrow irradiation</keyword>
  <keyword>melphalan</keyword>
  <keyword>multiple myeloma</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>
  <!-- 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/NCT01665014
org study id: TMI MM1
nct id: NCT01665014
lead sponsor: 
has dmc: Yes
The purpose of this study is to evaluate if the use total marrow irradiation (TMI) as a sole
      preparation for the first autologous hematopoietic stem cell transplantation (autoHSCT)
      followed by high-dose melphalan used prior to second autoHSCT is safe and effective in
      patients with multiple myeloma (MM).
AutoHSCT is a standard treatment of patients with MM. According to soem clinical evidence
      double autoHSCT provides survival advantage compared to a single procedure. Most frequently
      used conditioning regimen consists pf high doses of melphalan (HD-MEL). In some studies it
      was used in combination with total body irradiation (TBI), which, however was associated with
      significant toxicity. In our center the standard procedure includes TBI as a single treatment
      at 1st autoHSCT and HD-Mel at 2nd autoHSCT.

      As in MM malignant plasma cells are localized almost exclusively in bone marrow there is
      rationale to limit irradiation to bones. For this purpose in the current study we substitute
      TBI with TMI. Additional boosts are provided for active sites of disease based on PET/CT
      imaging. Our intention is to minimize toxicity while maintaining the treatment efficacy.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression-free survival
time frame: three years
measure: Rate of complete and very good partial responses
time frame: six months
measure: Rate of severe adverse events
time frame: one year
arm group label: Total marrow irradiation
arm group type: Experimental
description: Double autologous hematopoietic stem cell transplantation using TMI and HD-Mel
intervention type: Radiation
intervention name: Total marrow irradiation
description: Mobilization of stem cells with the use of cytarabine 1.6 g/m2 followed by filgrastim 480 ug/d. Conditioning for the 1st autoHSCT: total marrow irradiation 4 Gy on days -3,-2,-1 (total 12 Gy). Conditioning for 2nd autoHSCT performed 3-4 months after the 1st one: melphalan 100 mg/m2 on days -2,-3 (total 200 mg/m2)
arm group label: Total marrow irradiation
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Sebastian Giebel, MD
role: Principal Investigator
affiliation: Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland
last name: Sebastian Giebel, MD
phone: 0048322788523
email: sgiebel@io.gliwice.pl
facility: 
contact: 
investigator: 
country: Poland
citation: Somlo G, Spielberger R, Frankel P, Karanes C, Krishnan A, Parker P, Popplewell L, Sahebi F, Kogut N, Snyder D, Liu A, Schultheiss T, Forman S, Wong JY. Total marrow irradiation: a new ablative regimen as part of tandem autologous stem cell transplantation for patients with multiple myeloma. Clin Cancer Res. 2011 Jan 1;17(1):174-82. doi: 10.1158/1078-0432.CCR-10-1912. Epub 2010 Nov 3.
PMID: 21047977
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell