<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/NCT04420494</url>
  </required_header>
  <id_info>
    <org_study_id>ZS-2433</org_study_id>
    <nct_id>NCT04420494</nct_id>
  </id_info>
  <brief_title>Umbilical Cord Blood Treatment for Refractory Immune Cytopenia</brief_title>
  <official_title>Umbilical Cord Blood Treatment for Refractory Immune Cytopenia: a Single-arm Prospective Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Peking Union Medical College Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Peking Union Medical College Hospital</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>
      Immune-related hematocytopenia is a type of immunity Inflammatory cytopenia-mediated&#xD;
      diseases, hormones and immunosuppressants are its first-line treatment. However, conventional&#xD;
      immunosuppressants are ineffective or have a high recurrence rate. And some patients are not&#xD;
      effective for these treatments, due to infection of blood cells, bleeding, decreased quality&#xD;
      of life, and even severe death. There is currently no effective method for such patients.&#xD;
      This study intends to recruit IRIC patients, give cord blood infusion, observe its efficacy&#xD;
      and safety, and detect changes in inflammation-related indicators before and after treatment.&#xD;
      There are no relevant reports at China and abroad. This study can provide new treatment&#xD;
      options for patients with IRIC.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Immune-related hematocytopenia (IRC- autoimmune hemolytic anemia (AIHA), Evans syndrome,&#xD;
      acquired acquired pure red aplastic anemia (PRCA), autoimmune disease with cytopenia, etc.)&#xD;
      is a type of immunity Inflammatory cytopenia-mediated diseases, hormones and&#xD;
      immunosuppressants are its first-line treatment. However, conventional immunosuppressants are&#xD;
      ineffective or have a high recurrence rate, known as refractory immune-related cytopenia&#xD;
      (IRIC). Subsequent other second-line treatments such as other immunosuppressive agents, CD20&#xD;
      monoclonal antibodies, anti-human lymphocyte immunoglobulin (ATG ), And even splenectomy have&#xD;
      problems such as high side effects, high price, slow onset of effect, and low efficiency. And&#xD;
      some patients are not effective for these treatments, due to infection of blood cells,&#xD;
      bleeding, decreased quality of life, and even severe death. There is currently no effective&#xD;
      method for such patients.&#xD;
&#xD;
      Studies have shown that certain factors induce the loss of autoimmune tolerance in IRC&#xD;
      patients, and the autoantigens of bone marrow hematopoietic cells are presented by dendritic&#xD;
      cells, stimulating T cells, resulting in B cell activation and hyperfunction to produce&#xD;
      specific autoantibodies; among them, helper T cells ( Th) Abnormal activation of 17 and&#xD;
      follicular helper T cells (Tfh), the negative regulatory function of regulatory T cells and&#xD;
      regulatory B cells weakens, and also promotes the production of autoantibodies. However, the&#xD;
      bone marrow hematopoietic function caused by autoantibodies destroying or inhibiting&#xD;
      hematopoietic cells is low or ineffective. Studies have pointed out that hematopoietic&#xD;
      therapy is the key to curative treatment. At present, the safety and effectiveness of&#xD;
      umbilical cord blood in the treatment of malignant / non-malignant hematological diseases&#xD;
      have been confirmed and are widely used. In non-myeloablative therapy, the common adverse&#xD;
      reactions of umbilical cord blood transfusion are increased body temperature, hemoglobinuria&#xD;
      and DMSO side effects, and these adverse reactions can be adjusted by themselves and can be&#xD;
      eliminated within 48 hours. Umbilical cord blood is rich in hematopoietic stem / progenitor&#xD;
      cells, NK, regulatory T cells, and MSC can all have therapeutic effects on IRC to varying&#xD;
      degrees, and the immune cells in cord blood are mostly naive, immature immune cells,&#xD;
      Therefore, the incidence and severity of graft-versus-host disease (GVHD) after clinical&#xD;
      application of unrelated umbilical cord blood are low, avoiding a series of complications and&#xD;
      high costs caused by complex GVHD prevention and treatment technology. At the same time,&#xD;
      regulatory T cells (Treg) in umbilical cord blood account for about 10% of all lymphocytes.&#xD;
      They are a group of lymphocytes with negative regulatory immune responses. They usually play&#xD;
      an important role in maintaining self-tolerance and avoiding excessive immune responses to&#xD;
      damage the body. Function, its infusion can directly treat IRC. The number of NK cells in IRC&#xD;
      patients is reduced, the immune monitoring effect is weakened, the homeostasis of the immune&#xD;
      system cannot be maintained, and the immune cell function is hyperactive, leading to&#xD;
      morbidity. However, CD16 + CD56 + NK cells are abundant in cord blood, and the amount of CD3&#xD;
      + T cells is the same as that in bone marrow. Most researchers believe that NK cells play an&#xD;
      important role in immune surveillance in the body's immune system. They can regulate&#xD;
      downstream immune cells by secreting cytokines or cytotoxicity, and thus play a protective&#xD;
      role in autoimmune diseases. In addition, mesenchymal stem cells (MSC) contained in cord&#xD;
      blood are another type of stem cells with high self-renewal and multi-directional&#xD;
      differentiation potential, which can differentiate into a variety of tissue cells other than&#xD;
      hematopoietic cells and have hematopoietic support , Immunomodulation, tissue repair and&#xD;
      other functions are conducive to the restoration of bone marrow function in patients with&#xD;
      hematopoietic disorders; at the same time, MSCs also have immunomodulatory, anti-inflammatory&#xD;
      and tissue repair functions, which can reduce graft-versus-host disease (GVHD) and other&#xD;
      transplant-related complications. Umbilical cord blood has the advantages of quick access,&#xD;
      convenient source, no harm to donors, low HLA matching requirements, low incidence of&#xD;
      graft-versus-host disease (GVHD) and low degree, making the clinical application of cord&#xD;
      blood more and more widely , Its clinical treatment advantages have become increasingly&#xD;
      prominent.&#xD;
&#xD;
      On May 1, 2009, the General Office of the Ministry of Health issued a notice on the first&#xD;
      batch of the third category of medical technology that allows clinical application,&#xD;
      clarifying that umbilical cord blood hematopoietic stem cell therapy technology is approved&#xD;
      for clinical application as a third category of medical technology. In addition, the&#xD;
      Technical Specification for Hematopoietic Stem Cell Transplantation clearly states that cord&#xD;
      blood hematopoietic stem cells for clinical application should be provided by the cord blood&#xD;
      hematopoietic stem cell bank approved by the National Health and Family Planning Commission.&#xD;
      On July 4, 2019, the National Health and Welfare Commission issued a document that clearly&#xD;
      stated that there are currently 7 cord blood hematopoietic stem cell banks that have passed&#xD;
      the national acceptance practice, namely Shandong Bank, Beijing Bank, Tianjin Bank, Shanghai&#xD;
      Bank, Zhejiang Bank, Guangdong Bank and Sichuan library.&#xD;
&#xD;
      This study intends to recruit IRIC patients, give cord blood infusion, observe its efficacy&#xD;
      and safety, and detect changes in inflammation-related indicators before and after treatment.&#xD;
      There are no relevant reports at China and abroad. This study can provide new treatment&#xD;
      options for patients with IRIC. If it proves effective, it may rewrite the treatment&#xD;
      guidelines for such diseases; in addition, this study may also provide a theoretical basis&#xD;
      for expanding the application of cord blood in the future.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Anticipated">April 20, 2022</start_date>
  <completion_date type="Anticipated">April 20, 2022</completion_date>
  <primary_completion_date type="Anticipated">April 20, 2022</primary_completion_date>
  <phase>N/A</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>Clinical remission rate Clinical remission rate Clinical remission rate Clinical remission rate: including CR and PR</measure>
    <time_frame>0.5~24 months</time_frame>
    <description>Units of Measure %</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Umbilical Cord Blood</condition>
  <condition>Refractory Immune Cytopenia</condition>
  <arm_group>
    <arm_group_label>Patients treated with umbilical cord blood</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Umbilical Cord Blood</intervention_name>
    <description>The diagnosis is definitely immune cytopenia (IRC), including autoimmune hemolytic anemia (AIHA, Hgb &lt;100g / L, acquired pure red aplastic anemia (PRCA, Hgb &lt;100g / L, EVANS syndrome , Hgb &lt;100g / L and / or platelet count &lt;30 × 109 / L, or blood cell reduction secondary to immune diseases (the same as the treatment indications, or neutrophils &lt;0.5 × 109 / L), at least after hormone therapy Patients who are ineffective (did not reach PR after 4 weeks of hormone therapy) or who have not achieved PR after 3-5 mg / kg / d of cyclosporine. These patients would be treated with umbilical cord blood.</description>
    <arm_group_label>Patients treated with umbilical cord blood</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18-80 years (adults, elderly), gender is not limited;&#xD;
&#xD;
               -  The diagnosis is definitely immune cytopenia (IRC), including autoimmune&#xD;
                  hemolytic anemia (AIHA, Hgb &lt;100g / L, acquired pure red aplastic anemia (PRCA,&#xD;
                  Hgb &lt;100g / L, EVANS syndrome ES, Hgb &lt;100g / L and / or platelet count &lt;30 × 109&#xD;
                  / L, or cytopenia secondary to immune diseases (same treatment as before, or&#xD;
                  neutrophils &lt;0.5 × 109 / L), at least after hormones If the treatment is not&#xD;
                  effective (PR has not been achieved after 4 weeks of hormone therapy) or&#xD;
                  cyclosporine 3-5mg / kg / d has not reached PR for half a year.&#xD;
&#xD;
                    -  Those without abnormal cardiac function, abnormal liver function (total&#xD;
                       bilirubin 1.5 × ULN, ALT, AST≤3.0 × ULN), and abnormal renal function (serum&#xD;
                       creatinine≤1.0 × ULN) ④ ECOG score 0, 1 or 2; ⑤ Except autoimmunity There is&#xD;
                       no other secondary disease other than the disease; ⑥ Clearly understand the&#xD;
                       content of the trial, voluntarily participate in and complete this trial,&#xD;
                       and voluntarily sign an informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age &lt;18 years old or&gt; 80 years old;&#xD;
&#xD;
               -  Patients with tumors (except carcinoma in situ); ③ Uncontrollable systemic&#xD;
                  infections or other serious diseases; ④ Women who are pregnant or lactating; ⑤&#xD;
                  Patients with mental illness and potential impact Those with severe mental and&#xD;
                  mental illness who signed the informed consent form and followed up with the&#xD;
                  medical consultation;&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Peking Union Medical College Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100730</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yali Y Du, master</last_name>
      <phone>+8618910575941</phone>
      <email>yali_crazy@126.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Peking Union Medical College Hospital</name>
      <address>
        <city>Beijing</city>
        <zip>100730</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yali Du, Master</last_name>
      <phone>+8618910575941</phone>
      <email>yali_crazy@126.com</email>
    </contact>
    <investigator>
      <last_name>Bing Han, Doctor</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>April 2020</verification_date>
  <study_first_submitted>April 27, 2020</study_first_submitted>
  <study_first_submitted_qc>June 5, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>June 5, 2020</last_update_submitted>
  <last_update_submitted_qc>June 5, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 9, 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>Anemia</mesh_term>
    <mesh_term>Leukopenia</mesh_term>
    <mesh_term>Thrombocytopenia</mesh_term>
  </condition_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/NCT04420494
org study id: ZS-2433
nct id: NCT04420494
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Immune-related hematocytopenia is a type of immunity Inflammatory cytopenia-mediated
      diseases, hormones and immunosuppressants are its first-line treatment. However, conventional
      immunosuppressants are ineffective or have a high recurrence rate. And some patients are not
      effective for these treatments, due to infection of blood cells, bleeding, decreased quality
      of life, and even severe death. There is currently no effective method for such patients.
      This study intends to recruit IRIC patients, give cord blood infusion, observe its efficacy
      and safety, and detect changes in inflammation-related indicators before and after treatment.
      There are no relevant reports at China and abroad. This study can provide new treatment
      options for patients with IRIC.
Immune-related hematocytopenia (IRC- autoimmune hemolytic anemia (AIHA), Evans syndrome,
      acquired acquired pure red aplastic anemia (PRCA), autoimmune disease with cytopenia, etc.)
      is a type of immunity Inflammatory cytopenia-mediated diseases, hormones and
      immunosuppressants are its first-line treatment. However, conventional immunosuppressants are
      ineffective or have a high recurrence rate, known as refractory immune-related cytopenia
      (IRIC). Subsequent other second-line treatments such as other immunosuppressive agents, CD20
      monoclonal antibodies, anti-human lymphocyte immunoglobulin (ATG ), And even splenectomy have
      problems such as high side effects, high price, slow onset of effect, and low efficiency. And
      some patients are not effective for these treatments, due to infection of blood cells,
      bleeding, decreased quality of life, and even severe death. There is currently no effective
      method for such patients.

      Studies have shown that certain factors induce the loss of autoimmune tolerance in IRC
      patients, and the autoantigens of bone marrow hematopoietic cells are presented by dendritic
      cells, stimulating T cells, resulting in B cell activation and hyperfunction to produce
      specific autoantibodies; among them, helper T cells ( Th) Abnormal activation of 17 and
      follicular helper T cells (Tfh), the negative regulatory function of regulatory T cells and
      regulatory B cells weakens, and also promotes the production of autoantibodies. However, the
      bone marrow hematopoietic function caused by autoantibodies destroying or inhibiting
      hematopoietic cells is low or ineffective. Studies have pointed out that hematopoietic
      therapy is the key to curative treatment. At present, the safety and effectiveness of
      umbilical cord blood in the treatment of malignant / non-malignant hematological diseases
      have been confirmed and are widely used. In non-myeloablative therapy, the common adverse
      reactions of umbilical cord blood transfusion are increased body temperature, hemoglobinuria
      and DMSO side effects, and these adverse reactions can be adjusted by themselves and can be
      eliminated within 48 hours. Umbilical cord blood is rich in hematopoietic stem / progenitor
      cells, NK, regulatory T cells, and MSC can all have therapeutic effects on IRC to varying
      degrees, and the immune cells in cord blood are mostly naive, immature immune cells,
      Therefore, the incidence and severity of graft-versus-host disease (GVHD) after clinical
      application of unrelated umbilical cord blood are low, avoiding a series of complications and
      high costs caused by complex GVHD prevention and treatment technology. At the same time,
      regulatory T cells (Treg) in umbilical cord blood account for about 10% of all lymphocytes.
      They are a group of lymphocytes with negative regulatory immune responses. They usually play
      an important role in maintaining self-tolerance and avoiding excessive immune responses to
      damage the body. Function, its infusion can directly treat IRC. The number of NK cells in IRC
      patients is reduced, the immune monitoring effect is weakened, the homeostasis of the immune
      system cannot be maintained, and the immune cell function is hyperactive, leading to
      morbidity. However, CD16 + CD56 + NK cells are abundant in cord blood, and the amount of CD3
      + T cells is the same as that in bone marrow. Most researchers believe that NK cells play an
      important role in immune surveillance in the body's immune system. They can regulate
      downstream immune cells by secreting cytokines or cytotoxicity, and thus play a protective
      role in autoimmune diseases. In addition, mesenchymal stem cells (MSC) contained in cord
      blood are another type of stem cells with high self-renewal and multi-directional
      differentiation potential, which can differentiate into a variety of tissue cells other than
      hematopoietic cells and have hematopoietic support , Immunomodulation, tissue repair and
      other functions are conducive to the restoration of bone marrow function in patients with
      hematopoietic disorders; at the same time, MSCs also have immunomodulatory, anti-inflammatory
      and tissue repair functions, which can reduce graft-versus-host disease (GVHD) and other
      transplant-related complications. Umbilical cord blood has the advantages of quick access,
      convenient source, no harm to donors, low HLA matching requirements, low incidence of
      graft-versus-host disease (GVHD) and low degree, making the clinical application of cord
      blood more and more widely , Its clinical treatment advantages have become increasingly
      prominent.

      On May 1, 2009, the General Office of the Ministry of Health issued a notice on the first
      batch of the third category of medical technology that allows clinical application,
      clarifying that umbilical cord blood hematopoietic stem cell therapy technology is approved
      for clinical application as a third category of medical technology. In addition, the
      Technical Specification for Hematopoietic Stem Cell Transplantation clearly states that cord
      blood hematopoietic stem cells for clinical application should be provided by the cord blood
      hematopoietic stem cell bank approved by the National Health and Family Planning Commission.
      On July 4, 2019, the National Health and Welfare Commission issued a document that clearly
      stated that there are currently 7 cord blood hematopoietic stem cell banks that have passed
      the national acceptance practice, namely Shandong Bank, Beijing Bank, Tianjin Bank, Shanghai
      Bank, Zhejiang Bank, Guangdong Bank and Sichuan library.

      This study intends to recruit IRIC patients, give cord blood infusion, observe its efficacy
      and safety, and detect changes in inflammation-related indicators before and after treatment.
      There are no relevant reports at China and abroad. This study can provide new treatment
      options for patients with IRIC. If it proves effective, it may rewrite the treatment
      guidelines for such diseases; in addition, this study may also provide a theoretical basis
      for expanding the application of cord blood in the future.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Clinical remission rate Clinical remission rate Clinical remission rate Clinical remission rate: including CR and PR
time frame: 0.5~24 months
description: Units of Measure %
arm group label: Patients treated with umbilical cord blood
arm group type: Experimental
intervention type: Other
intervention name: Umbilical Cord Blood
description: The diagnosis is definitely immune cytopenia (IRC), including autoimmune hemolytic anemia (AIHA, Hgb <100g / L, acquired pure red aplastic anemia (PRCA, Hgb <100g / L, EVANS syndrome , Hgb <100g / L and / or platelet count <30 × 109 / L, or blood cell reduction secondary to immune diseases (the same as the treatment indications, or neutrophils <0.5 × 109 / L), at least after hormone therapy Patients who are ineffective (did not reach PR after 4 weeks of hormone therapy) or who have not achieved PR after 3-5 mg / kg / d of cyclosporine. These patients would be treated with umbilical cord blood.
arm group label: Patients treated with umbilical cord blood
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
investigator: 
country: China
responsible party type: Sponsor
mesh term: Anemia
mesh term: Leukopenia
mesh term: Thrombocytopenia
sharing ipd: Undecided