<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/NCT04436367</url>
  </required_header>
  <id_info>
    <org_study_id>999920118</org_study_id>
    <secondary_id>20-H-N118</secondary_id>
    <nct_id>NCT04436367</nct_id>
  </id_info>
  <brief_title>Retrospective Study of Patients With Severe Aplastic Anemia Who Developed High Risk Clonal Evolution With Chromosome 7 Abnormalities After Immunosuppressive Therapy</brief_title>
  <official_title>Retrospective Study of Patients With Severe Aplastic Anemia Who Developed High Risk Clonal Evolution With Chromosome 7 Abnormalities After Immunosuppressive Therapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institutes of Health Clinical Center (CC)</source>
  <brief_summary>
    <textblock>
      Background:&#xD;
&#xD;
      Severe aplastic anemia (SAA) is a form of bone marrow failure. It usually results from a&#xD;
&#xD;
      cytotoxic T cell attack on the marrow stem cell. Two treatments can be used for SAA. One is&#xD;
      allogeneic hematopoietic stem cell transplant (HSCT). The other is immunosuppressive&#xD;
      treatment (IST). In most cases, HSCT or IST works. But for some people, clonal evolution&#xD;
      occurs after IST. One of the most common forms of clonal evolution is chromosome 7&#xD;
      abnormalities. These have a poor prognosis. HSCT can be used to treat them. Researchers do&#xD;
      not know why clonal evolution happens. They want to look at data from past studies to learn&#xD;
      more.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      To compare the data of people with SAA who developed chromosome 7 abnormalities between those&#xD;
      who ultimately received HSCT versus those who received chemotherapy alone or supportive care.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
      Adults and children with SAA who were enrolled on NHLBI protocol 12-H-0150, 06-H-0034,&#xD;
      03-H-0249, 03-H-0193, 00-H-0032, or 90-H-0146&#xD;
&#xD;
      Design:&#xD;
&#xD;
      This study uses data from past studies. The participants in those studies have allowed their&#xD;
      data to be used in future research.&#xD;
&#xD;
      Researchers will review participants medical records. They will collect clinical data, such&#xD;
      as notes, test results, and imaging scans. They will also collect the research data gathered&#xD;
      as part of the original study.&#xD;
&#xD;
      Researchers will enter the data into an in-house database. It is password protected. All data&#xD;
      will be kept in secure network drives or in sites that comply with NIH security rules.&#xD;
&#xD;
      Other studies may be added in the future.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Severe aplastic anemia (SAA) is a form of bone marrow failure in most cases is the result of&#xD;
      a cytotoxic T cell attack on the marrow stem cell. It is effectively treated in most patients&#xD;
      with either immunosuppressive treatment (IST) or allogeneic hematopoietic stem cell&#xD;
      transplant (HSCT). However, after IST, 'clonal evolution' is a significant complication in&#xD;
      about 15% of patients, presenting as either a new cytogenetic abnormality or morphological&#xD;
      evidence of myeloid malignancy. In particular, the development of chromosome 7 abnormalities&#xD;
      is considered high risk and is associated with poor prognosis. The optimal treatment of&#xD;
      chromosome 7 abnormalities following SAA is not defined though HSCT is widely offered.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 15, 2020</start_date>
  <completion_date type="Actual">March 15, 2022</completion_date>
  <primary_completion_date type="Actual">April 22, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Characteristics and outcomes of SAA patients who developed chromosome 7 abnormalities</measure>
    <time_frame>Between the Period of 1990 to 2020</time_frame>
    <description>To compare characteristics and outcomes of SAA patients who developed chromosome 7 abnormalities between those who ultimately received HSCT versus those who received chemotherapy alone or supportive care</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical predictors for the development of chromosome 7 abnormalities such as age, gender, baseline laboratory value</measure>
    <time_frame>Between the Period of 1990 to 2020</time_frame>
    <description>To identify clinical predictors for the development of chromosome 7 abnormalities such as age, gender, baseline laboratory values, time from diagnosis to initial treatment, relapse, and number of IST treatments</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ascertain the natural history of patients with a chromosome 7 abnormality on karyotype</measure>
    <time_frame>Between the Period of 1990 to 2020</time_frame>
    <description>Ascertain the natural history of patients with a chromosome 7 abnormality on karyotype who were surveilled until the development of an overt myeloid neoplasm</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Morphological predictors in the bone marrow for progression to an overt myeloid neoplasm</measure>
    <time_frame>Between the Period of 1990 to 2020</time_frame>
    <description>To identify morphological predictors in the bone marrow for progression to an overt myeloid neoplasm in those with without an overt myeloid neoplasm at the time of development of chromosome 7 abnormalities</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">38</enrollment>
  <condition>Severe Aplastic Anemia</condition>
  <arm_group>
    <arm_group_label>SAA patients with Monosomy 7</arm_group_label>
    <description>Severe Aplastic Anemia Patients who Developed High Risk Clonal Evolution with Chromosome 7 Abnormalities after Immunosuppressive Therapy</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        SAA Subjects who developed chromosome 7 abnormalities&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        -  Subjects will not be recruited for this study. This is a retrospective chart review.&#xD;
&#xD;
        Patients who opted out of future use of data on their prior studies will be excluded from&#xD;
        this study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Emma M Groarke, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Heart, Lung, and Blood Institute (NHLBI)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Heart, Lung and Blood Institute (NHLBI)</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20892</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>June 17, 2020</study_first_submitted>
  <study_first_submitted_qc>June 17, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 18, 2020</study_first_posted>
  <last_update_submitted>September 27, 2022</last_update_submitted>
  <last_update_submitted_qc>September 27, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 29, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Cytogenic Abnormality</keyword>
  <keyword>Natural History</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anemia</mesh_term>
    <mesh_term>Anemia, Aplastic</mesh_term>
    <mesh_term>Congenital Abnormalities</mesh_term>
  </condition_browse>
  <!-- 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/NCT04436367
org study id: 999920118
secondary id: 20-H-N118
nct id: NCT04436367
lead sponsor: 
Background:

      Severe aplastic anemia (SAA) is a form of bone marrow failure. It usually results from a

      cytotoxic T cell attack on the marrow stem cell. Two treatments can be used for SAA. One is
      allogeneic hematopoietic stem cell transplant (HSCT). The other is immunosuppressive
      treatment (IST). In most cases, HSCT or IST works. But for some people, clonal evolution
      occurs after IST. One of the most common forms of clonal evolution is chromosome 7
      abnormalities. These have a poor prognosis. HSCT can be used to treat them. Researchers do
      not know why clonal evolution happens. They want to look at data from past studies to learn
      more.

      Objective:

      To compare the data of people with SAA who developed chromosome 7 abnormalities between those
      who ultimately received HSCT versus those who received chemotherapy alone or supportive care.

      Eligibility:

      Adults and children with SAA who were enrolled on NHLBI protocol 12-H-0150, 06-H-0034,
      03-H-0249, 03-H-0193, 00-H-0032, or 90-H-0146

      Design:

      This study uses data from past studies. The participants in those studies have allowed their
      data to be used in future research.

      Researchers will review participants medical records. They will collect clinical data, such
      as notes, test results, and imaging scans. They will also collect the research data gathered
      as part of the original study.

      Researchers will enter the data into an in-house database. It is password protected. All data
      will be kept in secure network drives or in sites that comply with NIH security rules.

      Other studies may be added in the future.
Severe aplastic anemia (SAA) is a form of bone marrow failure in most cases is the result of
      a cytotoxic T cell attack on the marrow stem cell. It is effectively treated in most patients
      with either immunosuppressive treatment (IST) or allogeneic hematopoietic stem cell
      transplant (HSCT). However, after IST, 'clonal evolution' is a significant complication in
      about 15% of patients, presenting as either a new cytogenetic abnormality or morphological
      evidence of myeloid malignancy. In particular, the development of chromosome 7 abnormalities
      is considered high risk and is associated with poor prognosis. The optimal treatment of
      chromosome 7 abnormalities following SAA is not defined though HSCT is widely offered.
observational model: Cohort
time perspective: Retrospective
measure: Characteristics and outcomes of SAA patients who developed chromosome 7 abnormalities
time frame: Between the Period of 1990 to 2020
description: To compare characteristics and outcomes of SAA patients who developed chromosome 7 abnormalities between those who ultimately received HSCT versus those who received chemotherapy alone or supportive care
measure: Clinical predictors for the development of chromosome 7 abnormalities such as age, gender, baseline laboratory value
time frame: Between the Period of 1990 to 2020
description: To identify clinical predictors for the development of chromosome 7 abnormalities such as age, gender, baseline laboratory values, time from diagnosis to initial treatment, relapse, and number of IST treatments
measure: Ascertain the natural history of patients with a chromosome 7 abnormality on karyotype
time frame: Between the Period of 1990 to 2020
description: Ascertain the natural history of patients with a chromosome 7 abnormality on karyotype who were surveilled until the development of an overt myeloid neoplasm
measure: Morphological predictors in the bone marrow for progression to an overt myeloid neoplasm
time frame: Between the Period of 1990 to 2020
description: To identify morphological predictors in the bone marrow for progression to an overt myeloid neoplasm in those with without an overt myeloid neoplasm at the time of development of chromosome 7 abnormalities
arm group label: SAA patients with Monosomy 7
description: Severe Aplastic Anemia Patients who Developed High Risk Clonal Evolution with Chromosome 7 Abnormalities after Immunosuppressive Therapy
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 2 Years
maximum age: N/A
healthy volunteers: No
last name: Emma M Groarke, M.D.
role: Principal Investigator
affiliation: National Heart, Lung, and Blood Institute (NHLBI)
facility: 
country: United States
responsible party type: Sponsor
mesh term: Anemia
mesh term: Anemia, Aplastic
mesh term: Congenital Abnormalities