<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/NCT02990819</url>
  </required_header>
  <id_info>
    <org_study_id>15-011733</org_study_id>
    <secondary_id>15BT022</secondary_id>
    <nct_id>NCT02990819</nct_id>
  </id_info>
  <brief_title>Alpha/Beta T and CD19+ Depleted Peripheral Stem Cells for Patients With Primary Immunodeficiencies</brief_title>
  <official_title>Phase II Study for Patients With Primary Immunodeficiencies Using and Cd19+ Depleted Unrelated Donor or Partially Matched Related Donor Peripheral Stem Cells</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Children's Hospital of Philadelphia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Children's Hospital of Philadelphia</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase II trial to determine the ability of a reduced intensity conditioning regimen&#xD;
      to allow successful engraftment with alpha/beta T and CD19+ depleted peripheral stem cell&#xD;
      grafts from unrelated or partially matched related donors. There are two conditioning&#xD;
      regimens depending upon patient diagnosis and age.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase II trial to determine the ability of a reduced intensity conditioning regimen&#xD;
      to allow successful engraftment with alpha/beta T and CD19+ depleted peripheral stem cell&#xD;
      grafts from unrelated or partially matched related donors. There are two conditioning&#xD;
      regimens depending upon patient diagnosis and age.&#xD;
&#xD;
      The study will include patients 0-25 years with PID, including immune dysregulation syndromes&#xD;
      for which hematopoietic stem cell transplant is indicated.&#xD;
&#xD;
      Treatment: Either conditioning regimen (listed below) followed by alpha/beta T and CD19+&#xD;
      depleted donor peripheral stem cells&#xD;
&#xD;
        1. Reduced intensity conditioning with busulfan x 8 doses, fludarabine 40 mg/m2 x 4,&#xD;
           thiotepa 5 mg/kg x 2, anti-thymocyte globulin (ATG) 3 mg/kg x 3.&#xD;
&#xD;
           OR&#xD;
&#xD;
        2. Myeloablative regimen with busulfan x 16 doses or Daily for four days, fludarabine 30&#xD;
           mg/m2 x 5, thiotepa 5 mg/kg x 2, ATG 3 mg/kg x 2.&#xD;
&#xD;
           OR&#xD;
&#xD;
        3. Immunotherapy regimen on days -9, 8, 7 with anti-thymocyte globulin 3 mg/kg/day (for&#xD;
           severe combined immunodeficiency patients only).&#xD;
&#xD;
        4. Infusion of alpha/beta T and CD19+ depleted donor peripheral stem cells.&#xD;
&#xD;
        5. Follow up, including evaluation of chimerism and immune reconstitution.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date>December 2016</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">December 2023</primary_completion_date>
  <phase>Phase 2</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>T-depleted stem cell infusion</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Event free survival</measure>
    <time_frame>One year</time_frame>
    <description>Event free survival in greater than 20 percent donor cells at one year for patients with primary immunodeficiencies (PID) who receive unrelated or partially matched related donor peripheral stem cell grafts which have been alpha/beta T depleted and CD19 depleted</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Stable engraftment</measure>
    <time_frame>One year</time_frame>
    <description>Stable engraftment in greater than 20 percent donor cells at one year for patients with primary immunodeficiencies (PID) who receive unrelated or partially matched related donor peripheral stem cell grafts which have been alpha/beta T depleted and CD19 depleted</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Severity of graft vs. host disease (GVHD)</measure>
    <time_frame>One and two years</time_frame>
    <description>Severity of acute and chronic graft vs host disease (GVHD), incidence of mixed chimerism, primary and secondary graft rejection, and immune reconstitution at one and two years</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of graft vs. host disease (GVHD)</measure>
    <time_frame>One and two years</time_frame>
    <description>Evaluation of incidence of chronic graft vs host disease (GVHD), incidence of mixed chimerism, primary and secondary graft rejection, and immune reconstitution at one and two years</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Immunodeficiencies</condition>
  <condition>Immune Dysregulation Syndromes</condition>
  <arm_group>
    <arm_group_label>Reduced intensity regimen</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Conditioning regimen is dependent on patient diagnosis and age. Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete alpha/beta T and CD19+ peripheral stem cells. Standard of care reduced intensity conditioning will include Busulfan, Fludarabine, Thiotepa followed by stem cell infusion.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Myeloablative regimen</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Conditioning regimen is dependent on patient diagnosis and age. Patients with chronic granulomatous disease or Wiskott-Aldrich syndrome will receive cyclophosphamide in lieu of thiotepa to ensure engraftment.&#xD;
Myeloablative regimen with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete alpha/beta T and CD19+ peripheral stem cells. Standard of care myeloablative regimen will include Busulfan, Fludarabine, Thiotepa, or Cyclophosphamide followed by stem cell infusion.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Immunotherapy</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Conditioning regimen is dependent on patient diagnosis and age. Severe combined immunodeficiency (SCID) patients will be conditioned with immunotherapy only followed by stem cell transplant using the CliniMACs device to deplete alpha/beta T and CD19+ peripheral stem cells. Immunotherapy regimen will include anti-thymocyte globulin followed by stem cell infusion.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Apha/beta T and CD19+ cell depletion using CliniMACS device</intervention_name>
    <description>Stem cells will be processed using the CliniMACS device for alpha/beta and CD19+ T cell depletion. Processing of cells using the CliniMACS will occur in accordance with the Investigator Brochure and Technical Manual following the laboratory standard operating procedures (SOPs) and using aseptic technique.</description>
    <arm_group_label>Immunotherapy</arm_group_label>
    <arm_group_label>Myeloablative regimen</arm_group_label>
    <arm_group_label>Reduced intensity regimen</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Ages 0-25 years at time of enrollment&#xD;
&#xD;
          2. Diseases:&#xD;
&#xD;
               -  Immunodeficiencies for which allogeneic hematopoietic stem cell transplant is&#xD;
                  indicated, including severe combined immunodeficiencies, immunodeficiency&#xD;
                  polyendocrinopathy X-linked syndrome (IPEX), X-linked lymphoproliferative&#xD;
                  disease, chronic granulomatous disease, Wiskott-Aldrich syndrome (WAS), hyperIgM,&#xD;
                  and other life-threatening immunodeficiencies.&#xD;
&#xD;
               -  Immune dysregulation syndromes, including refractory or recurrent hemophagocytic&#xD;
                  lymphohistiocytosis, hemophagocytic lymphohistiocytosis (HLH) with genetic&#xD;
                  mutations, refractory multisystemic Langerhans cell histiocytosis, other&#xD;
                  macrophage activating syndrome (MAS) refractory to standard therapy.&#xD;
&#xD;
          3. Clinical status&#xD;
&#xD;
               -  Lansky or Karnofsky performance &gt;=60&#xD;
&#xD;
               -  Organ Function:&#xD;
&#xD;
                    1. Serum creatinine &lt;1.5 x upper limit of normal for age Hepatic: ALT &lt;=250;&#xD;
                       AST &lt;=350&#xD;
&#xD;
                    2. Cardiac shortening fraction &gt;=27%&#xD;
&#xD;
                    3. Bilirubin &lt;2.5x normal (unless elevation due to Gilberts disease).&#xD;
&#xD;
                    4. No active untreated infection&#xD;
&#xD;
          4. Signed informed consent&#xD;
&#xD;
          5. No HLA matched related donor available.&#xD;
&#xD;
          6. Females of childbearing potential must have negative pregnancy test.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Uncontrolled bacterial, viral or fungal infections&#xD;
&#xD;
          -  HLA matched related or unrelated donor able to donate mobilized peripheral stem cells.&#xD;
&#xD;
          -  Pregnant Females&#xD;
&#xD;
          -  Matched related donor available for bone marrow donation&#xD;
&#xD;
        Donors Selection Criteria:&#xD;
&#xD;
          -  Donor selection will comply with 21 CFR 1271&#xD;
&#xD;
          -  Unrelated donor matched or up to one antigen mismatch as per National Marrow Donor&#xD;
             Program (NMDP).&#xD;
&#xD;
          -  Haploidentical parent or sibling able to undergo mobilization for peripheral stem cell&#xD;
             collection. Maternal donor preferred over paternal donor if both equally&#xD;
             haploidentical.&#xD;
&#xD;
          -  Children's Hospital of Philadelphia (CHOP) Blood and Marrow Transplant (BMT)&#xD;
             procedures apply for determining donor eligibility, including donor screening and&#xD;
             testing for relevant communicable disease agents and diseases.&#xD;
&#xD;
          -  Unrelated donor identified through the National Marrow Donor Program (NMDP) and&#xD;
             fulfills the NMDP criteria for donation. Unrelated donor willing and able to undergo&#xD;
             mobilization of peripheral stem cells and apheresis&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>25 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nancy Bunin, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Children's Hospital of Philadelphia</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Barbara McGlynn, RN, BSN</last_name>
    <email>MCGLYNN@chop.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Children's Hospital of Philadelphia</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Barbara McGlynn, RN, BSN</last_name>
      <email>MCGLYNN@chop.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>December 5, 2016</study_first_submitted>
  <study_first_submitted_qc>December 8, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 13, 2016</study_first_posted>
  <last_update_submitted>July 14, 2023</last_update_submitted>
  <last_update_submitted_qc>July 14, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Children's Hospital of Philadelphia</investigator_affiliation>
    <investigator_full_name>Nancy Bunin</investigator_full_name>
    <investigator_title>Director, Blood and Marrow Transplant</investigator_title>
  </responsible_party>
  <keyword>Immunodeficiencies</keyword>
  <keyword>Immune dysregulation syndromes</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Primary Immunodeficiency Diseases</mesh_term>
    <mesh_term>Immunologic Deficiency Syndromes</mesh_term>
  </condition_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/NCT02990819
org study id: 15-011733
secondary id: 15BT022
nct id: NCT02990819
lead sponsor: 
has dmc: Yes
This is a Phase II trial to determine the ability of a reduced intensity conditioning regimen
      to allow successful engraftment with alpha/beta T and CD19+ depleted peripheral stem cell
      grafts from unrelated or partially matched related donors. There are two conditioning
      regimens depending upon patient diagnosis and age.
This is a Phase II trial to determine the ability of a reduced intensity conditioning regimen
      to allow successful engraftment with alpha/beta T and CD19+ depleted peripheral stem cell
      grafts from unrelated or partially matched related donors. There are two conditioning
      regimens depending upon patient diagnosis and age.

      The study will include patients 0-25 years with PID, including immune dysregulation syndromes
      for which hematopoietic stem cell transplant is indicated.

      Treatment: Either conditioning regimen (listed below) followed by alpha/beta T and CD19+
      depleted donor peripheral stem cells

        1. Reduced intensity conditioning with busulfan x 8 doses, fludarabine 40 mg/m2 x 4,
           thiotepa 5 mg/kg x 2, anti-thymocyte globulin (ATG) 3 mg/kg x 3.

           OR

        2. Myeloablative regimen with busulfan x 16 doses or Daily for four days, fludarabine 30
           mg/m2 x 5, thiotepa 5 mg/kg x 2, ATG 3 mg/kg x 2.

           OR

        3. Immunotherapy regimen on days -9, 8, 7 with anti-thymocyte globulin 3 mg/kg/day (for
           severe combined immunodeficiency patients only).

        4. Infusion of alpha/beta T and CD19+ depleted donor peripheral stem cells.

        5. Follow up, including evaluation of chimerism and immune reconstitution.
allocation: Non-Randomized
intervention model: Single Group Assignment
intervention model description: T-depleted stem cell infusion
primary purpose: Treatment
masking: None (Open Label)
measure: Event free survival
time frame: One year
description: Event free survival in greater than 20 percent donor cells at one year for patients with primary immunodeficiencies (PID) who receive unrelated or partially matched related donor peripheral stem cell grafts which have been alpha/beta T depleted and CD19 depleted
measure: Stable engraftment
time frame: One year
description: Stable engraftment in greater than 20 percent donor cells at one year for patients with primary immunodeficiencies (PID) who receive unrelated or partially matched related donor peripheral stem cell grafts which have been alpha/beta T depleted and CD19 depleted
measure: Severity of graft vs. host disease (GVHD)
time frame: One and two years
description: Severity of acute and chronic graft vs host disease (GVHD), incidence of mixed chimerism, primary and secondary graft rejection, and immune reconstitution at one and two years
measure: Incidence of graft vs. host disease (GVHD)
time frame: One and two years
description: Evaluation of incidence of chronic graft vs host disease (GVHD), incidence of mixed chimerism, primary and secondary graft rejection, and immune reconstitution at one and two years
arm group label: Reduced intensity regimen
arm group type: Other
description: Conditioning regimen is dependent on patient diagnosis and age. Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete alpha/beta T and CD19+ peripheral stem cells. Standard of care reduced intensity conditioning will include Busulfan, Fludarabine, Thiotepa followed by stem cell infusion.
arm group label: Myeloablative regimen
arm group type: Other
description: Conditioning regimen is dependent on patient diagnosis and age. Patients with chronic granulomatous disease or Wiskott-Aldrich syndrome will receive cyclophosphamide in lieu of thiotepa to ensure engraftment.
Myeloablative regimen with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete alpha/beta T and CD19+ peripheral stem cells. Standard of care myeloablative regimen will include Busulfan, Fludarabine, Thiotepa, or Cyclophosphamide followed by stem cell infusion.
arm group label: Immunotherapy
arm group type: Other
description: Conditioning regimen is dependent on patient diagnosis and age. Severe combined immunodeficiency (SCID) patients will be conditioned with immunotherapy only followed by stem cell transplant using the CliniMACs device to deplete alpha/beta T and CD19+ peripheral stem cells. Immunotherapy regimen will include anti-thymocyte globulin followed by stem cell infusion.
intervention type: Device
intervention name: Apha/beta T and CD19+ cell depletion using CliniMACS device
description: Stem cells will be processed using the CliniMACS device for alpha/beta and CD19+ T cell depletion. Processing of cells using the CliniMACS will occur in accordance with the Investigator Brochure and Technical Manual following the laboratory standard operating procedures (SOPs) and using aseptic technique.
arm group label: Immunotherapy
arm group label: Myeloablative regimen
arm group label: Reduced intensity regimen
criteria: 
gender: All
minimum age: N/A
maximum age: 25 Years
healthy volunteers: No
last name: Nancy Bunin, MD
role: Principal Investigator
affiliation: Children's Hospital of Philadelphia
last name: Barbara McGlynn, RN, BSN
email: MCGLYNN@chop.edu
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Children's Hospital of Philadelphia
investigator full name: Nancy Bunin
investigator title: Director, Blood and Marrow Transplant
mesh term: Primary Immunodeficiency Diseases
mesh term: Immunologic Deficiency Syndromes
sharing ipd: No