<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/NCT04451200</url>
  </required_header>
  <id_info>
    <org_study_id>BUSEQ-IPC 2020-006</org_study_id>
    <nct_id>NCT04451200</nct_id>
  </id_info>
  <brief_title>Sequential and Personalized PK-guided Busulfan Administration in the Frame of the Conditiong Regimen for Allo-HSCT in Patients With Malignant Hemopathies Ineligible for the Standard Myeloablative Conditioning</brief_title>
  <acronym>BUSEQ</acronym>
  <official_title>Sequential and Personalized Pharmacokinetic-guided Busulfan Administration in the Frame of the Conditiong Regimen for Allogeneic Haematopoietic Stem Cell Transplantation in Patients With Malignant Hemopathies Ineligible for the Standard Myeloablative Conditioning</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institut Paoli-Calmettes</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Institut Paoli-Calmettes</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Because the anti-leukemic activity of busulfan, this dug is largely used in graft&#xD;
      conditioning but in elderly and/or cormobid patienth an excess of toxicity is observed. This&#xD;
      study focus on the possibility of significanty reducing this toxicity by customizing the&#xD;
      doses of busulfan to individual PK parameters.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">November 2020</start_date>
  <completion_date type="Anticipated">December 2028</completion_date>
  <primary_completion_date type="Anticipated">November 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>non-relapse mortality evaluation</measure>
    <time_frame>100 days post graft</time_frame>
    <description>non-relapse mortality evaluation</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>incidence of grade 3 or 4 toxicities</measure>
    <time_frame>1 month</time_frame>
    <description>To evaluate toxicities linked to sequential bususlfan administration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>graft taking after sequential busulfan conditioning</measure>
    <time_frame>day 30 and day 100 post graft</time_frame>
    <description>incidence of hematological reconstituation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>incidence of transfusion needs for red blood cells</measure>
    <time_frame>day 30 post graft</time_frame>
    <description>number of transfusions after graft</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>incidence of transfusion needs for red blood cells</measure>
    <time_frame>day 60 post graft</time_frame>
    <description>number of transfusions after graft</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>incidence in graft taking after sequential busulfan conditioning</measure>
    <time_frame>day 100 post graft</time_frame>
    <description>Lymphocyte chimerism</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>anti-tumoral efficacy of sequential busulfan conditioning: incidence of acute GVH</measure>
    <time_frame>1 year</time_frame>
    <description>incidence of acute GVH</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>anti-tumoral efficacy of sequential busulfan conditioning: incidence of acute GVH</measure>
    <time_frame>5 years</time_frame>
    <description>incidence of acute GVH</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>the anti-tumoral efficacy of sequential busulfan conditioning: incidence of chronic GVH</measure>
    <time_frame>1 and 5 years</time_frame>
    <description>incidence of chronic GVH</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>the anti-tumoral efficacy of sequential busulfan conditioning: incidence of chronic GVH</measure>
    <time_frame>1 year</time_frame>
    <description>incidence of chronic GVH</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>anti-tumoral efficacy of sequential busulfan conditioning: progression-free survival</measure>
    <time_frame>5 years</time_frame>
    <description>progression-free survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>anti-tumoral efficacy of sequential busulfan conditioning: progression-free survival</measure>
    <time_frame>1 year</time_frame>
    <description>overall survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>anti-tumoral efficacy of sequential busulfan conditioning: progression-free survival</measure>
    <time_frame>5 years</time_frame>
    <description>overall survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>anti-tumoral efficacy of sequential busulfan conditioning: Incidence of relapse</measure>
    <time_frame>1 year</time_frame>
    <description>Incidence of relapse</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Differences between the theoretical target AUC and the measured a posteriori</measure>
    <time_frame>1 month</time_frame>
    <description>To study the pharmacokinetics of the sequential administration of busulfan</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">82</enrollment>
  <condition>Acute Leukemia</condition>
  <condition>Mielodysplasic Syndrome</condition>
  <condition>Myeloproliferative Neoplasm</condition>
  <arm_group>
    <arm_group_label>busulfan treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Personalized BU administration</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Busulfan Injection</intervention_name>
    <description>injections doses will be personalized by PK at days -7 and -4</description>
    <arm_group_label>busulfan treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult patient up to 65 years old&#xD;
&#xD;
          -  Acute leukemia, myelodysplastic syndrome or myeloproliferative neoplasia eligible for&#xD;
             an allogeneic transplant&#xD;
&#xD;
          -  Chemosensitive disease, in complete or partial or stable remission&#xD;
&#xD;
          -  Allograft from an identical HLA related donor, Haplo-identical or unrelated (HLA&#xD;
             compatibility from 8/10 to 10/10 according to HLA-A, -B, -C, -DR, -DQ allelics)&#xD;
&#xD;
          -  Signed consent to participate&#xD;
&#xD;
             -. Affiliation to a social security regimen or beneficiary of this regimen&#xD;
&#xD;
          -  Patient not eligible for standard myeloablative conditioning due to age&gt; = 45 years&#xD;
             and / or the presence of an HCT-CI comorbidity score&gt; = 3&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant woman, without effective contraception or breastfeeding&#xD;
&#xD;
          -  Person in emergency situation, patient deprived of liberty or placed under the&#xD;
             authority of a tutor,&#xD;
&#xD;
          -  Impossibility of undergoing medical follow-up of the trial for geographic, social or&#xD;
             psychological reasons&#xD;
&#xD;
          -  Contraindications to performing an allogeneic transplant&#xD;
&#xD;
          -  Previous allograft&#xD;
&#xD;
          -  Placental blood allograft&#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_contact>
    <last_name>Dominique Genre, MD</last_name>
    <phone>+33491223778</phone>
    <email>drci.up@ipc.unicancer.fr</email>
  </overall_contact>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>June 3, 2020</study_first_submitted>
  <study_first_submitted_qc>June 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 30, 2020</study_first_posted>
  <last_update_submitted>November 16, 2020</last_update_submitted>
  <last_update_submitted_qc>November 16, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 17, 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>Myeloproliferative Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Busulfan</mesh_term>
  </intervention_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/NCT04451200
org study id: BUSEQ-IPC 2020-006
nct id: NCT04451200
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
Because the anti-leukemic activity of busulfan, this dug is largely used in graft
      conditioning but in elderly and/or cormobid patienth an excess of toxicity is observed. This
      study focus on the possibility of significanty reducing this toxicity by customizing the
      doses of busulfan to individual PK parameters.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: non-relapse mortality evaluation
time frame: 100 days post graft
description: non-relapse mortality evaluation
measure: incidence of grade 3 or 4 toxicities
time frame: 1 month
description: To evaluate toxicities linked to sequential bususlfan administration
measure: graft taking after sequential busulfan conditioning
time frame: day 30 and day 100 post graft
description: incidence of hematological reconstituation
measure: incidence of transfusion needs for red blood cells
time frame: day 30 post graft
description: number of transfusions after graft
measure: incidence of transfusion needs for red blood cells
time frame: day 60 post graft
description: number of transfusions after graft
measure: incidence in graft taking after sequential busulfan conditioning
time frame: day 100 post graft
description: Lymphocyte chimerism
measure: anti-tumoral efficacy of sequential busulfan conditioning: incidence of acute GVH
time frame: 1 year
description: incidence of acute GVH
measure: anti-tumoral efficacy of sequential busulfan conditioning: incidence of acute GVH
time frame: 5 years
description: incidence of acute GVH
measure: the anti-tumoral efficacy of sequential busulfan conditioning: incidence of chronic GVH
time frame: 1 and 5 years
description: incidence of chronic GVH
measure: the anti-tumoral efficacy of sequential busulfan conditioning: incidence of chronic GVH
time frame: 1 year
description: incidence of chronic GVH
measure: anti-tumoral efficacy of sequential busulfan conditioning: progression-free survival
time frame: 5 years
description: progression-free survival
measure: anti-tumoral efficacy of sequential busulfan conditioning: progression-free survival
time frame: 1 year
description: overall survival
measure: anti-tumoral efficacy of sequential busulfan conditioning: progression-free survival
time frame: 5 years
description: overall survival
measure: anti-tumoral efficacy of sequential busulfan conditioning: Incidence of relapse
time frame: 1 year
description: Incidence of relapse
measure: Differences between the theoretical target AUC and the measured a posteriori
time frame: 1 month
description: To study the pharmacokinetics of the sequential administration of busulfan
arm group label: busulfan treatment
arm group type: Experimental
description: Personalized BU administration
intervention type: Drug
intervention name: Busulfan Injection
description: injections doses will be personalized by PK at days -7 and -4
arm group label: busulfan treatment
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Dominique Genre, MD
phone: +33491223778
email: drci.up@ipc.unicancer.fr
responsible party type: Sponsor
mesh term: Myeloproliferative Disorders
mesh term: Busulfan
sharing ipd: No