<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/NCT03236220</url>
  </required_header>
  <id_info>
    <org_study_id>2015PHB220</org_study_id>
    <nct_id>NCT03236220</nct_id>
  </id_info>
  <brief_title>Effect of NAC on the Hematopoietic Reconstitution After Haploidentical Hematopoietic Stem Cell Transplantation</brief_title>
  <official_title>Effect of the Prophylactic Intervention of N-acetyl-L-cysteine (NAC) on the Incidence of Poor Graft Function and Prolonged Isolated Thrombocytopenia in Acute Leukemia Patients After Haploidentical Hematopoietic Stem Cell Transplantation</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>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>
      The aim of the study is to evaluate the efficacy of the prophylactic administration of&#xD;
      N-acetyl-L-cysteine (NAC) in acute leukemia patients with complete remission pre- and&#xD;
      post-allotransplant on the occurrence of poor graft function (PGF) and prolonged isolated&#xD;
      thrombocytopenia (PT) after haploidentical hematopoietic stem cell transplantation.&#xD;
      Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment of&#xD;
      malignant hematopoietic diseases. However, the delayed hematopoietic reconstitution,&#xD;
      including PGF and PT, remain serious complication after allo-HSCT, and the effective&#xD;
      therapeutic strategies are limited. In murine studies, endothelial cells have been identified&#xD;
      as a key cellular component supporting hematopoietic stem cells in the bone marrow&#xD;
      microenvironment. Our previous prospective nested case-control study suggested that the&#xD;
      frequency of bone marrow endothelial cells was markedly reduced in patients with PGF or PT.&#xD;
      Moreover, our recent study further identified reduced bone marrow endothelial cells (&lt;0.1%)&#xD;
      pre-allotransplant was associated with significant higher incidences of PGF or PT after&#xD;
      allo-HSCT. In addition, NAC treatment in vitro could quantitatively and functionally improve&#xD;
      bone marrow endothelial cells derived from the patients with PGF or PT. Therefore, bone&#xD;
      marrow endothelial cells (&lt;0.1%) pre-allotransplant can be used to identify patients with a&#xD;
      higher incidence of PGF or PT to provide timely prophylactic intervention of NAC to prevent&#xD;
      the occurrence of delayed hematopoietic reconstitution post-transplant. The study hypothesis:&#xD;
      Prophylactic intervention of NAC pre- and post-allotransplant could reduce the incidence of&#xD;
      PGF and PT in acute leukemia patients after haploidentical hematopoietic stem cell&#xD;
      transplantation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Acute leukemia patients with complete remission, whose bone marrow endothelial cells were&#xD;
      less than 0.1% detected before haploidentical hematopoietic stem cell transplantation,&#xD;
      receive NAC (orally at dosages of 400mg 3 times per day). NAC treatment begins from 14 days&#xD;
      pre-allotransplant to 2 months after-allotransplant continuously in the absence of disease&#xD;
      progression or unacceptable toxicity. The effect of NAC on hematopoietic stem cells,&#xD;
      megakaryocytes, immunologic subsets, and the elements of bone marrow microenvironment will be&#xD;
      monitored pre- and post-allotransplant.&#xD;
&#xD;
      Drug：N-acetyl-L-cysteine (NAC) is orally administrated at dosages of 400mg 3 times per day.&#xD;
      NAC treatment begins from 14 days pre-allotransplant to 2 months after-allotransplant&#xD;
      continuously in the absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      Participant：Acute leukemia patients with CR, whose bone marrow endothelial cells were less&#xD;
      than 0.1% detected before haploidentical hematopoietic stem cell transplantation.&#xD;
&#xD;
      Eligibility Ages Eligible for Study: 15-60 Years Genders Eligible for Study: Both Accepts The&#xD;
      trial will be terminated in following situation&#xD;
&#xD;
        1. Severe toxicity occurrence&#xD;
&#xD;
        2. Cumulative incidence of relapse increased) (≥ 30%)&#xD;
&#xD;
        3. Cumulative incidence of mortality increased (≥ 30%)&#xD;
&#xD;
        4. Cumulative incidence of severe graft-versus-host disease increased (≥ 30%)&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 1, 2017</start_date>
  <completion_date type="Actual">December 1, 2018</completion_date>
  <primary_completion_date type="Actual">July 1, 2018</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>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Open Label</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of poor graft function and prolonged isolated thrombocytopenia</measure>
    <time_frame>Participants will be followed for 2 months post-HSCT.</time_frame>
    <description>Number of participants with poor graft function and prolonged isolated thrombocytopenia will be calculated at 2-month post-HSCT.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of participants with treatment-related adverse events will be assessed by CTCAE v4.0 during oral administration of NAC.</measure>
    <time_frame>From 14 days pre-HSCT to 2 months post-HSCT.</time_frame>
    <description>Participants will be closely observed for NAC-related toxicities during the NAC administration until 2-month post-HSCT.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of NAC on hematopoietic stem cells, megakaryocytes and the elements of bone marrow microenvironment.</measure>
    <time_frame>Participants will be followed for 100 days post-HSCT.</time_frame>
    <description>Examine hematopoietic stem cells, megakaryocytes and the elements of bone&#xD;
marrow microenvironment by flow cytometry and bone marrow histological examination.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of GVHD</measure>
    <time_frame>Participants will be followed for 100 days post-HSCT.</time_frame>
    <description>Number of participants with I-IV aGVHD will be observed for 100 days post-HSCT.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of relapse</measure>
    <time_frame>Participants will be followed for 1 year post-HSCT.</time_frame>
    <description>Number of participants with morphologic relapse will be calculated at one year post-HSCT.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of viral infection</measure>
    <time_frame>Participants will be followed for 100 days post-HSCT.</time_frame>
    <description>Number of participants with viral infection(CMV,EBV,et al) will be observed for 100 days post-HSCT.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Non-relapse mortality</measure>
    <time_frame>Participants will be followed for 1 year post-HSCT.</time_frame>
    <description>Number of participants with non-relapse mortality will be observed for 1 year post-HSCT.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival</measure>
    <time_frame>Participants will be followed for 1 year post-HSCT.</time_frame>
    <description>Number of participants survived with progression-free will be observed for 1 year post-HSCT.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>Participants will be followed for 1 year post-HSCT.</time_frame>
    <description>Number of participants survived for 1 year post-HSCT will be calculated.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">35</enrollment>
  <condition>Haploidentical Hematopoietic Stem Cell Transplantation</condition>
  <arm_group>
    <arm_group_label>N-acetyl-L-cysteine group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Acute leukemia patients with complete remission, whose bone marrow endothelial cells were less than 0.1% detected before haploidentical hematopoietic stem cell transplantation, receive N-acetyl-L-cysteine.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>N-acetyl-L-cysteine</intervention_name>
    <description>Acute leukemia patients with complete remission, whose bone marrow endothelial cells were less than 0.1% detected before haploidentical hematopoietic stem cell transplantation, receive N-acetyl-L-cysteine (NAC) (orally at dosages of 400mg 3 times per day). NAC treatment begins from 14 days pre-allotransplant to 2 months after-allotransplant continuously in the absence of disease progression or unacceptable toxicity.</description>
    <arm_group_label>N-acetyl-L-cysteine group</arm_group_label>
    <other_name>NAC</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Acute leukemia patients with complete remission, whose bone marrow endothelial cells were&#xD;
        less than 0.1% detected before haploidentical hematopoietic stem cell transplantation；&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Bronchial asthma;&#xD;
&#xD;
          2. Allergic to N-acetyl-L-cystein&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>15 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Xiao-Jun Huang, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Peking University People's Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Peking University People's Hospital</name>
      <address>
        <city>Beijng</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>July 23, 2017</study_first_submitted>
  <study_first_submitted_qc>July 27, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 1, 2017</study_first_posted>
  <last_update_submitted>September 15, 2020</last_update_submitted>
  <last_update_submitted_qc>September 15, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 17, 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</investigator_title>
  </responsible_party>
  <keyword>haploidentical hematopoietic stem cell transplantation</keyword>
  <keyword>poor graft function</keyword>
  <keyword>prolonged isolated thrombocytopenia</keyword>
  <keyword>bone marrow endothelial cells</keyword>
  <keyword>N-acetyl-L-cysteine</keyword>
  <keyword>Acute leukemia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thrombocytopenia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acetylcysteine</mesh_term>
    <mesh_term>N-monoacetylcystine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03236220
org study id: 2015PHB220
nct id: NCT03236220
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The aim of the study is to evaluate the efficacy of the prophylactic administration of
      N-acetyl-L-cysteine (NAC) in acute leukemia patients with complete remission pre- and
      post-allotransplant on the occurrence of poor graft function (PGF) and prolonged isolated
      thrombocytopenia (PT) after haploidentical hematopoietic stem cell transplantation.
      Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment of
      malignant hematopoietic diseases. However, the delayed hematopoietic reconstitution,
      including PGF and PT, remain serious complication after allo-HSCT, and the effective
      therapeutic strategies are limited. In murine studies, endothelial cells have been identified
      as a key cellular component supporting hematopoietic stem cells in the bone marrow
      microenvironment. Our previous prospective nested case-control study suggested that the
      frequency of bone marrow endothelial cells was markedly reduced in patients with PGF or PT.
      Moreover, our recent study further identified reduced bone marrow endothelial cells (<0.1%)
      pre-allotransplant was associated with significant higher incidences of PGF or PT after
      allo-HSCT. In addition, NAC treatment in vitro could quantitatively and functionally improve
      bone marrow endothelial cells derived from the patients with PGF or PT. Therefore, bone
      marrow endothelial cells (<0.1%) pre-allotransplant can be used to identify patients with a
      higher incidence of PGF or PT to provide timely prophylactic intervention of NAC to prevent
      the occurrence of delayed hematopoietic reconstitution post-transplant. The study hypothesis:
      Prophylactic intervention of NAC pre- and post-allotransplant could reduce the incidence of
      PGF and PT in acute leukemia patients after haploidentical hematopoietic stem cell
      transplantation.
Acute leukemia patients with complete remission, whose bone marrow endothelial cells were
      less than 0.1% detected before haploidentical hematopoietic stem cell transplantation,
      receive NAC (orally at dosages of 400mg 3 times per day). NAC treatment begins from 14 days
      pre-allotransplant to 2 months after-allotransplant continuously in the absence of disease
      progression or unacceptable toxicity. The effect of NAC on hematopoietic stem cells,
      megakaryocytes, immunologic subsets, and the elements of bone marrow microenvironment will be
      monitored pre- and post-allotransplant.

      Drug：N-acetyl-L-cysteine (NAC) is orally administrated at dosages of 400mg 3 times per day.
      NAC treatment begins from 14 days pre-allotransplant to 2 months after-allotransplant
      continuously in the absence of disease progression or unacceptable toxicity.

      Participant：Acute leukemia patients with CR, whose bone marrow endothelial cells were less
      than 0.1% detected before haploidentical hematopoietic stem cell transplantation.

      Eligibility Ages Eligible for Study: 15-60 Years Genders Eligible for Study: Both Accepts The
      trial will be terminated in following situation

        1. Severe toxicity occurrence

        2. Cumulative incidence of relapse increased) (≥ 30%)

        3. Cumulative incidence of mortality increased (≥ 30%)

        4. Cumulative incidence of severe graft-versus-host disease increased (≥ 30%)
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Prevention
masking: None (Open Label)
masking description: Open Label
measure: Incidence of poor graft function and prolonged isolated thrombocytopenia
time frame: Participants will be followed for 2 months post-HSCT.
description: Number of participants with poor graft function and prolonged isolated thrombocytopenia will be calculated at 2-month post-HSCT.
measure: Number of participants with treatment-related adverse events will be assessed by CTCAE v4.0 during oral administration of NAC.
time frame: From 14 days pre-HSCT to 2 months post-HSCT.
description: Participants will be closely observed for NAC-related toxicities during the NAC administration until 2-month post-HSCT.
measure: Effect of NAC on hematopoietic stem cells, megakaryocytes and the elements of bone marrow microenvironment.
time frame: Participants will be followed for 100 days post-HSCT.
description: Examine hematopoietic stem cells, megakaryocytes and the elements of bone
marrow microenvironment by flow cytometry and bone marrow histological examination.
measure: Incidence of GVHD
time frame: Participants will be followed for 100 days post-HSCT.
description: Number of participants with I-IV aGVHD will be observed for 100 days post-HSCT.
measure: Incidence of relapse
time frame: Participants will be followed for 1 year post-HSCT.
description: Number of participants with morphologic relapse will be calculated at one year post-HSCT.
measure: Incidence of viral infection
time frame: Participants will be followed for 100 days post-HSCT.
description: Number of participants with viral infection(CMV,EBV,et al) will be observed for 100 days post-HSCT.
measure: Non-relapse mortality
time frame: Participants will be followed for 1 year post-HSCT.
description: Number of participants with non-relapse mortality will be observed for 1 year post-HSCT.
measure: Progression-free survival
time frame: Participants will be followed for 1 year post-HSCT.
description: Number of participants survived with progression-free will be observed for 1 year post-HSCT.
measure: Overall survival
time frame: Participants will be followed for 1 year post-HSCT.
description: Number of participants survived for 1 year post-HSCT will be calculated.
arm group label: N-acetyl-L-cysteine group
arm group type: Experimental
description: Acute leukemia patients with complete remission, whose bone marrow endothelial cells were less than 0.1% detected before haploidentical hematopoietic stem cell transplantation, receive N-acetyl-L-cysteine.
intervention type: Drug
intervention name: N-acetyl-L-cysteine
description: Acute leukemia patients with complete remission, whose bone marrow endothelial cells were less than 0.1% detected before haploidentical hematopoietic stem cell transplantation, receive N-acetyl-L-cysteine (NAC) (orally at dosages of 400mg 3 times per day). NAC treatment begins from 14 days pre-allotransplant to 2 months after-allotransplant continuously in the absence of disease progression or unacceptable toxicity.
arm group label: N-acetyl-L-cysteine group
other name: NAC
criteria: 
gender: All
minimum age: 15 Years
maximum age: 60 Years
healthy volunteers: No
last name: Xiao-Jun Huang, MD
role: Principal Investigator
affiliation: Peking University People's Hospital
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Peking University People's Hospital
investigator full name: Xiaojun Huang,MD
investigator title: Director
mesh term: Thrombocytopenia
mesh term: Acetylcysteine
mesh term: N-monoacetylcystine
sharing ipd: Undecided