<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/NCT03793517</url>
  </required_header>
  <id_info>
    <org_study_id>decitabine pre-HSCT in MRD+ AL</org_study_id>
    <nct_id>NCT03793517</nct_id>
  </id_info>
  <brief_title>Decitabine Plus mBU/CY for High Risk Acute Leukemia With MRD Pre-HSCT</brief_title>
  <official_title>Decitabine Plus mBU/CY for High Risk Acute Leukemia With Minimal Residual Disease Pre-HSCT</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Peking University People's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Peking University People's Hospital</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>
      Allogeneic haematopoietic stem cell transplantation (allo-HSCT) remains one of the currently&#xD;
      available curative therapies for acute leukemia (AL). Leukemia relapse is one of the mainly&#xD;
      causes of transplant failure. We reported previously that patients with high-risk molecular&#xD;
      biomarkers who still have detectable minimal residual disease(MRD) pre-HSCT were at very high&#xD;
      risk of relapse, with cumulative relapse rate of 50-80%. Decitabine has been demonstrated&#xD;
      efficacy in the treatment of patients with recurrent or refractory leukemia and&#xD;
      myelodysplastiv syndrome. It was reported that the combination of decitabine, with busufan&#xD;
      and cyclophosphamide as a preparative regimen for allo-HSCT using HLA-matching donors was&#xD;
      safe and effective. In this prospective, single-arm clinical trial, we aimed to examine the&#xD;
      efficacy of combining decitabine with modified busulfan and cyclophosphamide (mBU/CY) as a&#xD;
      preparative regimen for allo-HSCT in patients with very high-risk AL and detectable MRD&#xD;
      pre-HSCT.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients enrolled in this study would receive decitabine 200mg·m-2·d-1 on day -12 and -11&#xD;
      pre-HSCT. The conditioning therapy for human leukocyte antigen (HLA)-mismatched HSCT patients&#xD;
      was modified BU/CY plus ATG (thymoglobulin; Sang Stat, France) consisting of cytarabine&#xD;
      (Ara-C 4 g·m-2·d-1) intravenously on days -10 to -9, busulfan (BU 3.2 mg·kg-1·d-1)&#xD;
      intravenously on days -8 to -6, cyclophosphamide (CY 1.8 g·m-2·d-1), intravenously on days -5&#xD;
      to -4, semustine (Me-CCNU, 250 mg·m-2), orally once on day -3, and ATG (2.5 mg·kg-1·d-1)&#xD;
      intravenously on days -5 to -2. In matched sibling transplantations, patients received&#xD;
      hydroxycarbamide (80 mg·kg-1) orally on day -10 and a lower dose of Ara-C (2 g·m-2·d-1) on&#xD;
      day -9, but otherwise an identical regimen to the HLA-mismatched patients without ATG.&#xD;
&#xD;
      BM samples from patients were obtained to assess leukemia status after HSCT. The time points&#xD;
      that we monitored BM samples included at time of allo-HSCT; 1 month, 2 months, 3 months, 4.5&#xD;
      months, 6 months, 9 months, and 12 months after allo-HSCT; and every 6 months thereafter to&#xD;
      the defined endpoints or for at least until 5 years after transplantation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 1, 2018</start_date>
  <completion_date type="Anticipated">October 2026</completion_date>
  <primary_completion_date type="Anticipated">October 2023</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Patients enrolled in this study would receive decitabine 200mg·m-2·d-1 on day -12 and -11 pre-HSCT. The conditioning therapy for human leukocyte antigen (HLA)-mismatched HSCT patients was modified BU/CY plus ATG. In matched sibling transplantations, patients received hydroxycarbamide (80 mg·kg-1) orally on day -10 and a lower dose of Ara-C (2 g·m-2·d-1) on day -9, but otherwise an identical regimen to the HLA-mismatched patients without ATG.BM samples from patients would be obtained to assess leukemia status after HSCT. The time points that we monitored BM samples included at time of allo-HSCT; 1 month, 2 months, 3 months, 4.5 months, 6 months, 9 months, and 12 months after allo-HSCT; and every 6 months thereafter to the defined endpoints or for at least until 5 year after transplantation.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>1 year cumulative incidence of relapse</measure>
    <time_frame>1 year post allo-HSCT</time_frame>
    <description>The cumulative incidence of relapse at 1 year post allo-HSCT</description>
  </primary_outcome>
  <primary_outcome>
    <measure>2 year cumulative incidence of relapse</measure>
    <time_frame>2 years post allo-HSCT</time_frame>
    <description>The cumulative incidence of relapse at 2 years post allo-HSCT</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Non-relapse mortality</measure>
    <time_frame>1 year post allo-HSCT</time_frame>
    <description>The cumulative incidence of non-relapse mortality at 1 year post allo-HSCT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>1 year overall survival</measure>
    <time_frame>1 year post allo-HSCT</time_frame>
    <description>The overall survival at 1 year post allo-HSCT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>5 years overall survival</measure>
    <time_frame>5 years post allo-HSCT</time_frame>
    <description>The overall survival at 5 years post allo-HSCT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>1 year leukemia free survival</measure>
    <time_frame>1 year post allo-HSCT</time_frame>
    <description>The leukemia free survival at 1 years post allo-HSCT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>5 years leukemia free survival</measure>
    <time_frame>5 years post allo-HSCT</time_frame>
    <description>The leukemia free survival at 5 years post allo-HSCT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>engraftment</measure>
    <time_frame>100 days post allo-HSCT</time_frame>
    <description>The total neutrophil and platelet engraftment rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute graft versus host disease</measure>
    <time_frame>100 days post allo-HSCT</time_frame>
    <description>The cumulative incidence of grade II-IV acute graft versus host disease</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Chronic graft versus host disease</measure>
    <time_frame>1 years post allo-HSCT</time_frame>
    <description>The cumulative incidence of intermediate to severe chronic graft versus host disease</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">55</enrollment>
  <condition>Stem Cell Transplant Complications</condition>
  <condition>Leukemia, Myeloid, Acute</condition>
  <condition>Leukemia Relapse</condition>
  <arm_group>
    <arm_group_label>Decitabine plus mBU/CY for HLA-mismatched HSCT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Decitabine plus mBU/CY as precondition regimen for High Risk Acute Leukemia With MRD at the time of HLA-mismatched HSCT.&#xD;
Details:&#xD;
The conditioning therapy for human eukocyte antigen (HLA)-mismatched HSCT patients was decitabine plus modified BU/CY and ATG,consisting of decitabine 100mg·m-2·d-1 q12h on days-12 and -11,cytarabine (Ara-C 4 g·m-2·d-1) intravenously on days -10 to -9, busulfan (BU 3.2 mg·kg-1·d-1) intravenously on days -8 to -6, cyclophosphamide (CY 1.8 g·m-2·d-1), intravenously on days -5 to -4, simustine (Me-CCNU, 250 mg/m2), orally once on day -3, and ATG (2.5 mg·kg-1·d-1) intravenously on days -5 to -2.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Decitabine plus mBU/CY for matched sibling transplant</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Decitabine plus mBU/CY as precondition regimen for High Risk Acute Leukemia With MRD at the time of matched sibling transplant.&#xD;
Details:&#xD;
In matched sibling transplantations, patients received decitabine 100mg·m-2·d-1 q12h on days-12 and -11,hydroxycarbamide (80 mg/kg) orally on day -10 and a lower dose of Ara-C (2 g·m-2·d-1) on day -9, busulfan (BU 3.2 mg·kg-1·d-1) intravenously on days -8 to -6, cyclophosphamide (CY 1.8 g·m-2·d-1), intravenously on days -5 to -4, simustine (Me-CCNU, 250 mg/m2), orally once on day -3.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Decitabine</intervention_name>
    <description>Decitabine 200mg.m-2.d-1 intervanously on days -12 and -11</description>
    <arm_group_label>Decitabine plus mBU/CY for HLA-mismatched HSCT</arm_group_label>
    <arm_group_label>Decitabine plus mBU/CY for matched sibling transplant</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>mBU/CY and ATG</intervention_name>
    <description>Ara-C 4 g·m-2·d-1 intravenously on days -10 to -9 Busulfan (BU 3.2 mg·kg-1·d-1) intravenously on days -8 to -6, Cyclophosphamide (CY 1.8 g·m-2·d-1) intravenously on days -5 to -4 Simustine (Me-CCNU, 250 mg·m-2) orally once on day -3 ATG (2.5 mg·kg-1·d-1) intravenously on days -5 to -2</description>
    <arm_group_label>Decitabine plus mBU/CY for HLA-mismatched HSCT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>mBU/CY</intervention_name>
    <description>hydroxycarbamide (80 mg·kg-1) orally on day -10 Ara-C (2 g·m-2·d-1) on day -9 Busulfan (BU 3.2 mg·kg-1·d-1) intravenously on days -8 to -6, Cyclophosphamide (CY 1.8 g·m-2·d-1) intravenously on days -5 to -4 Simustine (Me-CCNU, 250 mg·m-2) orally once on day -3</description>
    <arm_group_label>Decitabine plus mBU/CY for matched sibling transplant</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  acute leukemia patients with MLL-r,TLS-ERG,or SIL-TAL1,whose minimal residual disease&#xD;
             were detectable pre-HSCT&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  pregnancy women&#xD;
&#xD;
          -  uncontrolled severe infection&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Xiao-Jun Huang</last_name>
    <role>Study Chair</role>
    <affiliation>Peking University People's Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Xiao-Jun Huang</last_name>
    <phone>+86 010 88326666</phone>
    <email>yanchenhua@vip.sina.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Chen-Hua Yan</last_name>
    <phone>+86 010 88326666</phone>
    <email>yanchenhua@vip.sina.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Peking University Institute of Hematology,Beijing</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100044</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Chen-hua Yan, MD</last_name>
      <phone>86 010 88326666</phone>
      <email>yanchenhua@vip.sina.com</email>
    </contact>
    <investigator>
      <last_name>Xiao-Jun Huang, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>December 23, 2018</study_first_submitted>
  <study_first_submitted_qc>January 3, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 4, 2019</study_first_posted>
  <last_update_submitted>March 9, 2020</last_update_submitted>
  <last_update_submitted_qc>March 9, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 10, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Peking University People's Hospital</investigator_affiliation>
    <investigator_full_name>Xiaojun Huang,MD</investigator_full_name>
    <investigator_title>Director of the Hematology Department</investigator_title>
  </responsible_party>
  <keyword>high risk acute myeloid leukemia</keyword>
  <keyword>hematopoietic stem cell transplantation</keyword>
  <keyword>leukemia relapse</keyword>
  <keyword>preparation regimen</keyword>
  <keyword>decitabine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Leukemia, Myeloid</mesh_term>
    <mesh_term>Leukemia, Myeloid, Acute</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Decitabine</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/NCT03793517
org study id: decitabine pre-HSCT in MRD+ AL
nct id: NCT03793517
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Allogeneic haematopoietic stem cell transplantation (allo-HSCT) remains one of the currently
      available curative therapies for acute leukemia (AL). Leukemia relapse is one of the mainly
      causes of transplant failure. We reported previously that patients with high-risk molecular
      biomarkers who still have detectable minimal residual disease(MRD) pre-HSCT were at very high
      risk of relapse, with cumulative relapse rate of 50-80%. Decitabine has been demonstrated
      efficacy in the treatment of patients with recurrent or refractory leukemia and
      myelodysplastiv syndrome. It was reported that the combination of decitabine, with busufan
      and cyclophosphamide as a preparative regimen for allo-HSCT using HLA-matching donors was
      safe and effective. In this prospective, single-arm clinical trial, we aimed to examine the
      efficacy of combining decitabine with modified busulfan and cyclophosphamide (mBU/CY) as a
      preparative regimen for allo-HSCT in patients with very high-risk AL and detectable MRD
      pre-HSCT.
Patients enrolled in this study would receive decitabine 200mg·m-2·d-1 on day -12 and -11
      pre-HSCT. The conditioning therapy for human leukocyte antigen (HLA)-mismatched HSCT patients
      was modified BU/CY plus ATG (thymoglobulin; Sang Stat, France) consisting of cytarabine
      (Ara-C 4 g·m-2·d-1) intravenously on days -10 to -9, busulfan (BU 3.2 mg·kg-1·d-1)
      intravenously on days -8 to -6, cyclophosphamide (CY 1.8 g·m-2·d-1), intravenously on days -5
      to -4, semustine (Me-CCNU, 250 mg·m-2), orally once on day -3, and ATG (2.5 mg·kg-1·d-1)
      intravenously on days -5 to -2. In matched sibling transplantations, patients received
      hydroxycarbamide (80 mg·kg-1) orally on day -10 and a lower dose of Ara-C (2 g·m-2·d-1) on
      day -9, but otherwise an identical regimen to the HLA-mismatched patients without ATG.

      BM samples from patients were obtained to assess leukemia status after HSCT. The time points
      that we monitored BM samples included at time of allo-HSCT; 1 month, 2 months, 3 months, 4.5
      months, 6 months, 9 months, and 12 months after allo-HSCT; and every 6 months thereafter to
      the defined endpoints or for at least until 5 years after transplantation.
allocation: Non-Randomized
intervention model: Single Group Assignment
intervention model description: Patients enrolled in this study would receive decitabine 200mg·m-2·d-1 on day -12 and -11 pre-HSCT. The conditioning therapy for human leukocyte antigen (HLA)-mismatched HSCT patients was modified BU/CY plus ATG. In matched sibling transplantations, patients received hydroxycarbamide (80 mg·kg-1) orally on day -10 and a lower dose of Ara-C (2 g·m-2·d-1) on day -9, but otherwise an identical regimen to the HLA-mismatched patients without ATG.BM samples from patients would be obtained to assess leukemia status after HSCT. The time points that we monitored BM samples included at time of allo-HSCT; 1 month, 2 months, 3 months, 4.5 months, 6 months, 9 months, and 12 months after allo-HSCT; and every 6 months thereafter to the defined endpoints or for at least until 5 year after transplantation.
primary purpose: Treatment
masking: None (Open Label)
measure: 1 year cumulative incidence of relapse
time frame: 1 year post allo-HSCT
description: The cumulative incidence of relapse at 1 year post allo-HSCT
measure: 2 year cumulative incidence of relapse
time frame: 2 years post allo-HSCT
description: The cumulative incidence of relapse at 2 years post allo-HSCT
measure: Non-relapse mortality
time frame: 1 year post allo-HSCT
description: The cumulative incidence of non-relapse mortality at 1 year post allo-HSCT
measure: 1 year overall survival
time frame: 1 year post allo-HSCT
description: The overall survival at 1 year post allo-HSCT
measure: 5 years overall survival
time frame: 5 years post allo-HSCT
description: The overall survival at 5 years post allo-HSCT
measure: 1 year leukemia free survival
time frame: 1 year post allo-HSCT
description: The leukemia free survival at 1 years post allo-HSCT
measure: 5 years leukemia free survival
time frame: 5 years post allo-HSCT
description: The leukemia free survival at 5 years post allo-HSCT
measure: engraftment
time frame: 100 days post allo-HSCT
description: The total neutrophil and platelet engraftment rate
measure: Acute graft versus host disease
time frame: 100 days post allo-HSCT
description: The cumulative incidence of grade II-IV acute graft versus host disease
measure: Chronic graft versus host disease
time frame: 1 years post allo-HSCT
description: The cumulative incidence of intermediate to severe chronic graft versus host disease
arm group label: Decitabine plus mBU/CY for HLA-mismatched HSCT
arm group type: Experimental
description: Decitabine plus mBU/CY as precondition regimen for High Risk Acute Leukemia With MRD at the time of HLA-mismatched HSCT.
Details:
The conditioning therapy for human eukocyte antigen (HLA)-mismatched HSCT patients was decitabine plus modified BU/CY and ATG,consisting of decitabine 100mg·m-2·d-1 q12h on days-12 and -11,cytarabine (Ara-C 4 g·m-2·d-1) intravenously on days -10 to -9, busulfan (BU 3.2 mg·kg-1·d-1) intravenously on days -8 to -6, cyclophosphamide (CY 1.8 g·m-2·d-1), intravenously on days -5 to -4, simustine (Me-CCNU, 250 mg/m2), orally once on day -3, and ATG (2.5 mg·kg-1·d-1) intravenously on days -5 to -2.
arm group label: Decitabine plus mBU/CY for matched sibling transplant
arm group type: Experimental
description: Decitabine plus mBU/CY as precondition regimen for High Risk Acute Leukemia With MRD at the time of matched sibling transplant.
Details:
In matched sibling transplantations, patients received decitabine 100mg·m-2·d-1 q12h on days-12 and -11,hydroxycarbamide (80 mg/kg) orally on day -10 and a lower dose of Ara-C (2 g·m-2·d-1) on day -9, busulfan (BU 3.2 mg·kg-1·d-1) intravenously on days -8 to -6, cyclophosphamide (CY 1.8 g·m-2·d-1), intravenously on days -5 to -4, simustine (Me-CCNU, 250 mg/m2), orally once on day -3.
intervention type: Drug
intervention name: Decitabine
description: Decitabine 200mg.m-2.d-1 intervanously on days -12 and -11
arm group label: Decitabine plus mBU/CY for HLA-mismatched HSCT
arm group label: Decitabine plus mBU/CY for matched sibling transplant
intervention type: Drug
intervention name: mBU/CY and ATG
description: Ara-C 4 g·m-2·d-1 intravenously on days -10 to -9 Busulfan (BU 3.2 mg·kg-1·d-1) intravenously on days -8 to -6, Cyclophosphamide (CY 1.8 g·m-2·d-1) intravenously on days -5 to -4 Simustine (Me-CCNU, 250 mg·m-2) orally once on day -3 ATG (2.5 mg·kg-1·d-1) intravenously on days -5 to -2
arm group label: Decitabine plus mBU/CY for HLA-mismatched HSCT
intervention type: Drug
intervention name: mBU/CY
description: hydroxycarbamide (80 mg·kg-1) orally on day -10 Ara-C (2 g·m-2·d-1) on day -9 Busulfan (BU 3.2 mg·kg-1·d-1) intravenously on days -8 to -6, Cyclophosphamide (CY 1.8 g·m-2·d-1) intravenously on days -5 to -4 Simustine (Me-CCNU, 250 mg·m-2) orally once on day -3
arm group label: Decitabine plus mBU/CY for matched sibling transplant
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: No
last name: Xiao-Jun Huang
role: Study Chair
affiliation: Peking University People's Hospital
last name: Xiao-Jun Huang
phone: +86 010 88326666
email: yanchenhua@vip.sina.com
last name: Chen-Hua Yan
phone: +86 010 88326666
email: yanchenhua@vip.sina.com
facility: 
status: Recruiting
contact: 
investigator: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Peking University People's Hospital
investigator full name: Xiaojun Huang,MD
investigator title: Director of the Hematology Department
mesh term: Leukemia
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myeloid, Acute
mesh term: Recurrence
mesh term: Decitabine
sharing ipd: No