<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/NCT03262220</url>
  </required_header>
  <id_info>
    <org_study_id>2017-00066</org_study_id>
    <nct_id>NCT03262220</nct_id>
  </id_info>
  <brief_title>Total Marrow Irradiation With Volumetric Arc Therapy for Patients Unfit for a 12 Gy TBI</brief_title>
  <official_title>Pilot Study of Dose Escalated Total Marrow Irradiation With Volumetric Arc Therapy for Patients With Hematological Malignancies Unfit for a Standard 12 Gy TBI Conditioning Regimen.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Thomas Zilli</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University Hospital, Geneva</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital, Geneva</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Total body irradiation (TBI) is a standard part of the conditioning regimen for bone marrow&#xD;
      transplantation (BMT). Several randomized trials have shown superior outcomes using TBI&#xD;
      compared with non TBI-containing regimens. Standard TBI is usually delivered over three days&#xD;
      for a total dose of 12 Gy with two daily fractions. However, as demonstrated by our group,&#xD;
      increasing the TBI dose above 10 Gy is not necessarily associated with better outcome in&#xD;
      patients undergoing allogenic BMT for hematologic malignancies. For this reason, patients&#xD;
      older than 40 or grafted after relapse are treated at our center with a reduced-dose 10 Gy&#xD;
      TBI regimen. This pilot study wishes to investigate in 10 patients with hematological&#xD;
      malignancies unfit for a standard 12 Gy TBI conditioning regimen a more targeted, conformal&#xD;
      form of treatment, referred as total marrow (TMI), using volumetric Arc Therapy (VMAT). Our&#xD;
      hypothesis is that using this technique that can allow deliver a higher total dose to the&#xD;
      target while at the same time assuring to the organs at risk (OAR) the same dose normally&#xD;
      delivered with a 10 Gy TBI we will improve the therapeutic ratio in these patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a feasibility prospective pilot study. Ten patients ≥ 40 years with hematologic&#xD;
      malignancies prior to Bone Marrow Transplant (BMT) will receive a dose escalated&#xD;
      hypofractionated Total Marrow Irradiation (TMI) (12 Gy in 3 fractions, daily, on 3&#xD;
      consecutive days).&#xD;
&#xD;
      The current project is a joint initiative in translational and clinical medical research&#xD;
      between the Radiation-oncology workgroup and the Bone Marrow transplant workgroup of&#xD;
      University Hospitals of Geneva (HUG).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 11, 2017</start_date>
  <completion_date type="Anticipated">April 2025</completion_date>
  <primary_completion_date type="Anticipated">April 2021</primary_completion_date>
  <phase>N/A</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>Grade II and III toxicity</measure>
    <time_frame>30 days after radiotherapy</time_frame>
    <description>(Seattle Regimen-related toxicity grade) 30 days after transplant in patients with hematologic malignancies treated with a dose-escalated hypofractionated VMAT-based TMI</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cumulative incidence of Transplant Related Mortality(TRM)</measure>
    <time_frame>100 days post-bone marrow transplantation</time_frame>
    <description>Defined as death occurring from causes that are different other than disease relapse post-transplant</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative incidence of Grade II Organ toxicity</measure>
    <time_frame>up to day 100 post-bone marrow transplantation</time_frame>
    <description>Seattle Regimen-related toxicity grade</description>
  </secondary_outcome>
  <enrollment type="Anticipated">10</enrollment>
  <condition>Haematological Malignancy</condition>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Volumetric Arc Therapy (VMAT)</intervention_name>
    <description>Total Marrow Irradiation: 12 Gy in 3 fractions of 4 Gy on 3 consecutive days with a concomitant simultaneous integrated boost (SIB) of 4.5 Gy x 3 fractions delivered to active bone marrow (ABM).</description>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Karnofsky performance status ≥ 70&#xD;
&#xD;
          -  Presence of any kind of haematological malignancy in complete remission (CR1, CR2 ore&#xD;
             CR3) at time of transplantation, with the exception of patients with myelodysplastic&#xD;
             syndrome.&#xD;
&#xD;
          -  Patients that are scheduled for a BMT either using stem cell derived from bone marrow&#xD;
             or peripheral blood stem cells.&#xD;
&#xD;
          -  Candidates to receive a 10 Gy TBI treatment.&#xD;
&#xD;
          -  Ability to stay still and lying on the treatment couch for at least 45 minutes.&#xD;
&#xD;
          -  Informed Consent as documented by signature.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Karnofsky performance status &lt;70 intended as a patient unable to work; able to live at&#xD;
             home and care for most personal needs with varying amount of assistance needed.&#xD;
&#xD;
          -  Concurrent treatment with other experimental drugs or other anti-cancer therapy.&#xD;
&#xD;
          -  Participation in another clinical trial and any concurrent treatment with any&#xD;
             investigational drug within 4 weeks prior to trial entry/randomisation.&#xD;
&#xD;
          -  Inability to comply with study and follow-up procedures.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Thomas Zilli, MD</last_name>
    <phone>+ 41 79 55 32 563</phone>
    <email>thomas.zilli@hcuge.ch</email>
  </overall_contact>
  <location>
    <facility>
      <name>University Hospital of Geneva</name>
      <address>
        <city>Genève</city>
        <zip>1205</zip>
        <country>Switzerland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Thomas Zilli, MD</last_name>
      <phone>+41 79 55 32 563</phone>
      <email>thomas.zilli@hcuge.ch</email>
    </contact>
    <investigator>
      <last_name>Giorgio Lamana, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Yves Chalandon, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>August 23, 2017</study_first_submitted>
  <study_first_submitted_qc>August 23, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 25, 2017</study_first_posted>
  <last_update_submitted>May 13, 2020</last_update_submitted>
  <last_update_submitted_qc>May 13, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">May 14, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University Hospital, Geneva</investigator_affiliation>
    <investigator_full_name>Thomas Zilli</investigator_full_name>
    <investigator_title>MD, PD, Médecin Adjoint Agrégé</investigator_title>
  </responsible_party>
  <keyword>Haematological malignancy</keyword>
  <keyword>Total Marrow Irradiation</keyword>
  <keyword>Volumetric Arc Therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Hematologic Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>No plan</ipd_description>
  </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/NCT03262220
org study id: 2017-00066
nct id: NCT03262220
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Total body irradiation (TBI) is a standard part of the conditioning regimen for bone marrow
      transplantation (BMT). Several randomized trials have shown superior outcomes using TBI
      compared with non TBI-containing regimens. Standard TBI is usually delivered over three days
      for a total dose of 12 Gy with two daily fractions. However, as demonstrated by our group,
      increasing the TBI dose above 10 Gy is not necessarily associated with better outcome in
      patients undergoing allogenic BMT for hematologic malignancies. For this reason, patients
      older than 40 or grafted after relapse are treated at our center with a reduced-dose 10 Gy
      TBI regimen. This pilot study wishes to investigate in 10 patients with hematological
      malignancies unfit for a standard 12 Gy TBI conditioning regimen a more targeted, conformal
      form of treatment, referred as total marrow (TMI), using volumetric Arc Therapy (VMAT). Our
      hypothesis is that using this technique that can allow deliver a higher total dose to the
      target while at the same time assuring to the organs at risk (OAR) the same dose normally
      delivered with a 10 Gy TBI we will improve the therapeutic ratio in these patients.
This is a feasibility prospective pilot study. Ten patients ≥ 40 years with hematologic
      malignancies prior to Bone Marrow Transplant (BMT) will receive a dose escalated
      hypofractionated Total Marrow Irradiation (TMI) (12 Gy in 3 fractions, daily, on 3
      consecutive days).

      The current project is a joint initiative in translational and clinical medical research
      between the Radiation-oncology workgroup and the Bone Marrow transplant workgroup of
      University Hospitals of Geneva (HUG).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Grade II and III toxicity
time frame: 30 days after radiotherapy
description: (Seattle Regimen-related toxicity grade) 30 days after transplant in patients with hematologic malignancies treated with a dose-escalated hypofractionated VMAT-based TMI
measure: Cumulative incidence of Transplant Related Mortality(TRM)
time frame: 100 days post-bone marrow transplantation
description: Defined as death occurring from causes that are different other than disease relapse post-transplant
measure: Cumulative incidence of Grade II Organ toxicity
time frame: up to day 100 post-bone marrow transplantation
description: Seattle Regimen-related toxicity grade
intervention type: Radiation
intervention name: Volumetric Arc Therapy (VMAT)
description: Total Marrow Irradiation: 12 Gy in 3 fractions of 4 Gy on 3 consecutive days with a concomitant simultaneous integrated boost (SIB) of 4.5 Gy x 3 fractions delivered to active bone marrow (ABM).
criteria: 
gender: All
minimum age: 40 Years
maximum age: 80 Years
healthy volunteers: No
last name: Thomas Zilli, MD
phone: + 41 79 55 32 563
email: thomas.zilli@hcuge.ch
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
country: Switzerland
responsible party type: Sponsor-Investigator
investigator affiliation: University Hospital, Geneva
investigator full name: Thomas Zilli
investigator title: MD, PD, Médecin Adjoint Agrégé
mesh term: Neoplasms
mesh term: Hematologic Neoplasms
sharing ipd: No
ipd description: No plan