<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/NCT02193724</url>
  </required_header>
  <id_info>
    <org_study_id>RETCELL</org_study_id>
    <nct_id>NCT02193724</nct_id>
  </id_info>
  <brief_title>Feasibility of Generating Pluripotent Stem Cells From Patients With Familial Retinoblastoma</brief_title>
  <official_title>Feasibility, Validation and Differentiation of Induced Pluripotent Stem Cells Produced From Patients With Heritable Retinoblastoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>St. Jude Children's Research Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Wisconsin, Madison</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>St. Jude Children's Research 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>
      The goal of this study is to determine if human RB1-deficient induced pluripotent stem cells&#xD;
      (iPSCs) can produce retina, and, furthermore, can give rise to retinoblastoma in culture.&#xD;
      This unique opportunity to study the initiation of retinoblastoma in the developing retina&#xD;
      will shed light on the cell of origin for retinoblastoma and allow the investigators to study&#xD;
      the earliest molecular and cellular events in retinoblastoma tumorigenesis.&#xD;
&#xD;
      OBJECTIVES:&#xD;
&#xD;
        -  To establish the feasibility of producing induced pluripotent stem cells (iPSCs) from&#xD;
           retinoblastoma patients with germline RB1 mutations (RB1-deficient iPSCs).&#xD;
&#xD;
        -  To validate human RB1-deficient iPSCs by confirming karyotype, pluripotency and RB1&#xD;
           mutation.&#xD;
&#xD;
        -  To differentiate the RB1-deficient iPSCs into retina as a model of the initiation of&#xD;
           retinoblastoma in the developing retina.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an observational study where a small skin cell sample or peripheral blood sample will&#xD;
      be used to produce iPSCs. After RB1-deficient iPSCs are produced, their karyotype and RB1&#xD;
      mutation will be confirmed and their pluripotency will be tested by studying the expression&#xD;
      of pluripotent genes and proteins according to standardized guidelines established for human&#xD;
      iPSCs. After validation of the RB1-deficient iPSCs, they will be differentiated in the&#xD;
      laboratory into retina following established protocols.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 4, 2014</start_date>
  <completion_date type="Actual">August 23, 2019</completion_date>
  <primary_completion_date type="Actual">August 23, 2019</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>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Number of samples which successfully produced iPSCs</measure>
    <time_frame>Once at enrollment</time_frame>
    <description>Skin biopsy or peripheral blood mononuclear cells will be collected from eligible, consenting participants and shipped directly to the University of Wisconsin for processing. All samples will be returned to the St. Jude investigator within two months of reprogramming for further analysis.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of samples with validated RB1-deficient iPSCs</measure>
    <time_frame>Once at enrollment</time_frame>
    <description>Samples will be analyzed for standard G band karyotype and FISH analysis (RB1 probe), targeted RB1 mutation (based on known mutation of patient from whom the sample was derived), and validation of pluripotency based on standard protocols.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of samples that differentiate human iPSCs toward an eye field fate</measure>
    <time_frame>Once at enrollment</time_frame>
    <description>The best available methodology will be utilized for analyses of the RB1-deficient iPSCs.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">15</enrollment>
  <condition>Retinoblastoma</condition>
  <arm_group>
    <arm_group_label>Retinoblastoma</arm_group_label>
    <description>Participants identified with heritable retinoblastoma will undergo a skin biopsy or blood draw to collect cells for processing and analysis.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Skin Biopsy</intervention_name>
    <description>A very small skin sample will be taken from the participant's arm. This will only be performed while the patient is under sedation for clinical purposes (e.g. exam under anesthesia, MRI, or other procedure requiring sedation).</description>
    <arm_group_label>Retinoblastoma</arm_group_label>
    <other_name>Punch Biopsy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Blood Draw</intervention_name>
    <description>About 1 teaspoon of blood will be drawn from the participant's arm or from a central line catheter if present. Blood collection will be done at the same time the participant has blood drawn for routine clinical care.</description>
    <arm_group_label>Retinoblastoma</arm_group_label>
    <other_name>Blood Sample</other_name>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Skin samples or peripheral blood samples to be used to generate pluripotent stem cells.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Participants will have a diagnosis of heritable retinoblastoma.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Research participant with heritable retinoblastoma and one of the following criteria:&#xD;
&#xD;
               -  Family history with RB1 mutation identified&#xD;
&#xD;
               -  Diagnosis of bilateral retinoblastoma&#xD;
&#xD;
               -  Diagnosis of unilateral retinoblastoma with RB1 mutation or MYCN amplification&#xD;
                  identified&#xD;
&#xD;
          -  Participant or legal guardian/representative is able and willing to provide written&#xD;
             informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participants who do not meet the inclusion criteria will be excluded.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Rachel C. Brennan, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>St. Jude Children's Research Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>St. Jude Children's Research Hospital</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.stjude.org</url>
    <description>St. Jude Children's Research Hospital</description>
  </link>
  <link>
    <url>http://www.stjude.org/protocols</url>
    <description>Clinical Trials Open at St. Jude</description>
  </link>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>July 16, 2014</study_first_submitted>
  <study_first_submitted_qc>July 16, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 18, 2014</study_first_posted>
  <last_update_submitted>October 21, 2020</last_update_submitted>
  <last_update_submitted_qc>October 21, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 23, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Heritable Retinoblastoma</keyword>
  <keyword>Familial Retinoblastoma</keyword>
  <keyword>Pluripotent Stem Cells</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Retinoblastoma</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/NCT02193724
org study id: RETCELL
nct id: NCT02193724
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The goal of this study is to determine if human RB1-deficient induced pluripotent stem cells
      (iPSCs) can produce retina, and, furthermore, can give rise to retinoblastoma in culture.
      This unique opportunity to study the initiation of retinoblastoma in the developing retina
      will shed light on the cell of origin for retinoblastoma and allow the investigators to study
      the earliest molecular and cellular events in retinoblastoma tumorigenesis.

      OBJECTIVES:

        -  To establish the feasibility of producing induced pluripotent stem cells (iPSCs) from
           retinoblastoma patients with germline RB1 mutations (RB1-deficient iPSCs).

        -  To validate human RB1-deficient iPSCs by confirming karyotype, pluripotency and RB1
           mutation.

        -  To differentiate the RB1-deficient iPSCs into retina as a model of the initiation of
           retinoblastoma in the developing retina.
This is an observational study where a small skin cell sample or peripheral blood sample will
      be used to produce iPSCs. After RB1-deficient iPSCs are produced, their karyotype and RB1
      mutation will be confirmed and their pluripotency will be tested by studying the expression
      of pluripotent genes and proteins according to standardized guidelines established for human
      iPSCs. After validation of the RB1-deficient iPSCs, they will be differentiated in the
      laboratory into retina following established protocols.
observational model: Cohort
time perspective: Prospective
measure: Number of samples which successfully produced iPSCs
time frame: Once at enrollment
description: Skin biopsy or peripheral blood mononuclear cells will be collected from eligible, consenting participants and shipped directly to the University of Wisconsin for processing. All samples will be returned to the St. Jude investigator within two months of reprogramming for further analysis.
measure: Number of samples with validated RB1-deficient iPSCs
time frame: Once at enrollment
description: Samples will be analyzed for standard G band karyotype and FISH analysis (RB1 probe), targeted RB1 mutation (based on known mutation of patient from whom the sample was derived), and validation of pluripotency based on standard protocols.
measure: Number of samples that differentiate human iPSCs toward an eye field fate
time frame: Once at enrollment
description: The best available methodology will be utilized for analyses of the RB1-deficient iPSCs.
arm group label: Retinoblastoma
description: Participants identified with heritable retinoblastoma will undergo a skin biopsy or blood draw to collect cells for processing and analysis.
intervention type: Other
intervention name: Skin Biopsy
description: A very small skin sample will be taken from the participant's arm. This will only be performed while the patient is under sedation for clinical purposes (e.g. exam under anesthesia, MRI, or other procedure requiring sedation).
arm group label: Retinoblastoma
other name: Punch Biopsy
intervention type: Other
intervention name: Blood Draw
description: About 1 teaspoon of blood will be drawn from the participant's arm or from a central line catheter if present. Blood collection will be done at the same time the participant has blood drawn for routine clinical care.
arm group label: Retinoblastoma
other name: Blood Sample
Skin samples or peripheral blood samples to be used to generate pluripotent stem cells.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Rachel C. Brennan, MD
role: Principal Investigator
affiliation: St. Jude Children's Research Hospital
facility: 
country: United States
url: http://www.stjude.org
description: St. Jude Children's Research Hospital
url: http://www.stjude.org/protocols
description: Clinical Trials Open at St. Jude
responsible party type: Sponsor
mesh term: Retinoblastoma