<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/NCT04400045</url>
  </required_header>
  <id_info>
    <org_study_id>NCPHOI-2020-04</org_study_id>
    <nct_id>NCT04400045</nct_id>
  </id_info>
  <brief_title>Low Dose Treosulfan Based Conditioning Regimen in HSCT for Nijmegen Breakage Syndrome</brief_title>
  <official_title>Clinical Open-label Phase 2 Study of Low Dose Treosulfan Based Conditioning Regimen Efficacy in Hematopoietic Stem Cell Transplantation for Children With Nijmegen Breakage Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Federal Research Institute of Pediatric Hematology, Oncology and Immunology</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Federal Research Institute of Pediatric Hematology, Oncology and Immunology</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of the current study is to evaluate the safety and efficacy of low dose treosulfan&#xD;
      based conditioning regimen in HSCT in Nijmegen breakage syndrome&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Nijmegen breakage syndrome (NBS) is a DNA repair disorder. The only curative option for&#xD;
      combine immunodeficiency in NBS is allogeneic hematopoietic stem cell transplantation (HSCT).&#xD;
      Standard myeloablative conditioning regimens in DNA repair disorders lead to increased&#xD;
      morbidity and mortality after HSCT. Low doses of alkylators are used to reduce toxicity&#xD;
      rates, which, however, increase the risks of mixed chimerism and graft failure. The data of&#xD;
      treosulfan usage in NBS are sparse. To evaluate the safety and efficacy of low dose&#xD;
      treosulfan based conditioning regimen in NBS, treosulfan 21g/m2 in combination with&#xD;
      fludarabine 150mg/mg, cyclophosphamide 40mg/kg, thymoglobulin (Genzyme) 5mg/kg and rituximab&#xD;
      100mg/m2 will be used from day -6 to -1 day, followed by stem cell infusion. The primary&#xD;
      endpoint is event-free survival, where graft failure, death, and malignancies are considered&#xD;
      as events.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">May 22, 2020</start_date>
  <completion_date type="Anticipated">May 2023</completion_date>
  <primary_completion_date type="Anticipated">May 2023</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>Event-free survival</measure>
    <time_frame>3 years after HSCT</time_frame>
    <description>Events: graft failure, death, malignancies</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>3 years after HSCT</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative incidence of engraftment</measure>
    <time_frame>100 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative incidence of graft failure</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative incidence of viral infections</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative incidence of acute graft versus host disease</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative incidence of chronic graft versus host disease</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of early organ toxicity</measure>
    <time_frame>100 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative incidence of transplant related mortality</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of long-term toxicity</measure>
    <time_frame>3 years</time_frame>
    <description>malignancies, non-malignant complications</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">10</enrollment>
  <condition>Nijmegen Breakage Syndrome</condition>
  <arm_group>
    <arm_group_label>intervention/treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Fludarabine 150mg/m2 (days -6, -5, -4, -3, -2) Treosulfan 21g/m2 (days -6, -5, -4) Cyclophosphamide 40mg/kg (days -3, -2) Thymoglobulin (Genzyme) 5mg/kg (days -5, -4) Rituximab 100mg/m2 (day -1) Stem cell infusion - day 0</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Treosulfan</intervention_name>
    <description>Treosulfan 21mg/m2 (days -6, -5, -4)</description>
    <arm_group_label>intervention/treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients aged ≥ 3 months and &lt; 21 years&#xD;
&#xD;
          2. Patients diagnosed with NBS eligible for an allogeneic HSCT&#xD;
&#xD;
          3. Signed written informed consent signed by a parent or legal guardian&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>3 Months</minimum_age>
    <maximum_age>21 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Dmitry Balashov, MD, PhD</last_name>
    <phone>+74952876570</phone>
    <phone_ext>6534</phone_ext>
    <email>bala8@yandex.ru</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Alexandra Laberko, MD</last_name>
    <phone>74952876570</phone>
    <phone_ext>6223</phone_ext>
    <email>alexandra.laberko@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>HSCT department</name>
      <address>
        <city>Moscow</city>
        <zip>117198</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dmitry Balashov, MD, PhD</last_name>
      <phone>+74952876570</phone>
      <phone_ext>6534</phone_ext>
      <email>bala8@yandex.ru</email>
    </contact>
  </location>
  <location_countries>
    <country>Russian Federation</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>May 19, 2020</study_first_submitted>
  <study_first_submitted_qc>May 19, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 22, 2020</study_first_posted>
  <last_update_submitted>June 23, 2020</last_update_submitted>
  <last_update_submitted_qc>June 23, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 25, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nijmegen Breakage Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Treosulfan</mesh_term>
  </intervention_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/NCT04400045
org study id: NCPHOI-2020-04
nct id: NCT04400045
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
The aim of the current study is to evaluate the safety and efficacy of low dose treosulfan
      based conditioning regimen in HSCT in Nijmegen breakage syndrome
Nijmegen breakage syndrome (NBS) is a DNA repair disorder. The only curative option for
      combine immunodeficiency in NBS is allogeneic hematopoietic stem cell transplantation (HSCT).
      Standard myeloablative conditioning regimens in DNA repair disorders lead to increased
      morbidity and mortality after HSCT. Low doses of alkylators are used to reduce toxicity
      rates, which, however, increase the risks of mixed chimerism and graft failure. The data of
      treosulfan usage in NBS are sparse. To evaluate the safety and efficacy of low dose
      treosulfan based conditioning regimen in NBS, treosulfan 21g/m2 in combination with
      fludarabine 150mg/mg, cyclophosphamide 40mg/kg, thymoglobulin (Genzyme) 5mg/kg and rituximab
      100mg/m2 will be used from day -6 to -1 day, followed by stem cell infusion. The primary
      endpoint is event-free survival, where graft failure, death, and malignancies are considered
      as events.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Event-free survival
time frame: 3 years after HSCT
description: Events: graft failure, death, malignancies
measure: Overall survival
time frame: 3 years after HSCT
measure: Cumulative incidence of engraftment
time frame: 100 days
measure: Cumulative incidence of graft failure
time frame: 3 years
measure: Cumulative incidence of viral infections
time frame: 1 year
measure: Cumulative incidence of acute graft versus host disease
time frame: 1 year
measure: Cumulative incidence of chronic graft versus host disease
time frame: 3 years
measure: Incidence of early organ toxicity
time frame: 100 days
measure: Cumulative incidence of transplant related mortality
time frame: 3 years
measure: Incidence of long-term toxicity
time frame: 3 years
description: malignancies, non-malignant complications
arm group label: intervention/treatment
arm group type: Experimental
description: Fludarabine 150mg/m2 (days -6, -5, -4, -3, -2) Treosulfan 21g/m2 (days -6, -5, -4) Cyclophosphamide 40mg/kg (days -3, -2) Thymoglobulin (Genzyme) 5mg/kg (days -5, -4) Rituximab 100mg/m2 (day -1) Stem cell infusion - day 0
intervention type: Drug
intervention name: Treosulfan
description: Treosulfan 21mg/m2 (days -6, -5, -4)
arm group label: intervention/treatment
criteria: 
gender: All
minimum age: 3 Months
maximum age: 21 Years
healthy volunteers: No
last name: Dmitry Balashov, MD, PhD
phone: +74952876570
phone ext: 6534
email: bala8@yandex.ru
last name: Alexandra Laberko, MD
phone: 74952876570
phone ext: 6223
email: alexandra.laberko@gmail.com
facility: 
status: Recruiting
contact: 
country: Russian Federation
responsible party type: Sponsor
mesh term: Nijmegen Breakage Syndrome
mesh term: Syndrome
mesh term: Treosulfan