<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/NCT03799224</url>
  </required_header>
  <id_info>
    <org_study_id>decitabine pre-HSCT for R/R AL</org_study_id>
    <nct_id>NCT03799224</nct_id>
  </id_info>
  <brief_title>Decitabine Plus mBU/CY Preconditioning for Relapse/Refractory Acute Leukemia</brief_title>
  <official_title>Decitabine Plus mBU/CY Preconditioning for Relapse/Refractory Acute Leukemia Patients Undergoing 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 relapse or refractory&#xD;
      AL were at very high risk of relapse post allo-HSCT, with cumulative relapse rate of 50-80%.&#xD;
      Decitabine has been demonstrated efficacy in the treatment of patients with recurrent or&#xD;
      refractory leukemia and myelodysplastic syndrome. It was reported that the combination of&#xD;
      decitabine, with busulfan and cyclophosphamide as a preparative regimen for allo-HSCT using&#xD;
      HLA-matching donors was safe and effective. In this prospective, single-arm clinical trial,&#xD;
      we aimed to examine the efficacy of combining decitabine with modified busulfan and&#xD;
      cyclophosphamide (mBU/CY) as a preparative regimen for allo-HSCT in recurrent and refractory&#xD;
      AL patients.&#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(bone marrow) samples from patients were obtained to assess leukemia status after HSCT. The&#xD;
      time points that we monitored BM samples included at time of allo-HSCT; 1 month, 2 months, 3&#xD;
      months, 4.5 months, 6 months, 9 months, and 12 months after allo-HSCT; and every 6 months&#xD;
      thereafter to 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">December 1, 2018</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2021</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] 1 year leukemia free survival</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>Relapse Leukemia</condition>
  <condition>Refractory Leukemia</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 recurrent and refractory acute leukemia at the time of HLA-mismatched HSCT&#xD;
Details:&#xD;
The conditioning therapy for human leukocyte 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, semustine (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 (minimal residual disease) 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, semustine (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 intravenously 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 Semustine (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 Semustine (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;
          -  patients with relapsed acute leukemia&#xD;
&#xD;
          -  patients with acute leukemia in the third（or more）complete remission (CR3) status&#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>
    <contact_backup>
      <last_name>Jing Liu, MD</last_name>
      <phone>86 010 88326666</phone>
      <email>liujing0245@bjmu.edu.cn</email>
    </contact_backup>
    <investigator>
      <last_name>Xiao-Jun Huang, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>May 2019</verification_date>
  <study_first_submitted>January 8, 2019</study_first_submitted>
  <study_first_submitted_qc>January 8, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 10, 2019</study_first_posted>
  <last_update_submitted>May 27, 2019</last_update_submitted>
  <last_update_submitted_qc>May 27, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">May 29, 2019</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>recurrent acute leukemia</keyword>
  <keyword>refractory acute leukemia</keyword>
  <keyword>preconditioning regimen</keyword>
  <keyword>allogeneic stem cell transplantation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</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/NCT03799224
org study id: decitabine pre-HSCT for R/R AL
nct id: NCT03799224
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 relapse or refractory
      AL were at very high risk of relapse post allo-HSCT, with cumulative relapse rate of 50-80%.
      Decitabine has been demonstrated efficacy in the treatment of patients with recurrent or
      refractory leukemia and myelodysplastic syndrome. It was reported that the combination of
      decitabine, with busulfan 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 recurrent and refractory
      AL patients.
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(bone marrow) 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] 1 year leukemia free survival
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 recurrent and refractory acute leukemia at the time of HLA-mismatched HSCT
Details:
The conditioning therapy for human leukocyte 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, semustine (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 (minimal residual disease) 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, semustine (Me-CCNU, 250 mg/m2), orally once on day -3.
intervention type: Drug
intervention name: Decitabine
description: Decitabine 200mg.m-2.d-1 intravenously 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 Semustine (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 Semustine (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: 
contact backup: 
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: Recurrence
mesh term: Decitabine
sharing ipd: No