<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/NCT03810196</url>
  </required_header>
  <id_info>
    <org_study_id>18-015286</org_study_id>
    <nct_id>NCT03810196</nct_id>
  </id_info>
  <brief_title>CD45RA Depleted Peripheral Stem Cell Addback for Viral or Fungal Infections Post TCRαβ/CD19 Depleted HSCT</brief_title>
  <official_title>CD45RA Depleted Peripheral Stem Cell Addback for Patients at Risk for Viral or Fungal Infections Post TCRαβ/CD19 Depleted Hematopoietic Stem Cell Transplant</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>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The major morbidities of allogeneic hematopoietic stem cell transplant with non-human&#xD;
      leukocyte antigen (HLA) matched siblings are graft vs host disease (GVHD) and life&#xD;
      threatening infections. T depletion of the donor hematopoietic stem cell graft is effective&#xD;
      in preventing GVHD, but immune reconstitution is slow, increasing the risk of infections. An&#xD;
      addback of donor CD45RA (naive T cells) depleted cells may improve immune reconstitution and&#xD;
      help decrease the risk of infections.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The risk of severe graft versus host disease (GVHD) is increased with the use of unrelated&#xD;
      and partially matched related donors. T cell depletion reduces the risk of severe GVHD, but&#xD;
      immune reconstitution is delayed. Important memory T cells that may protect patients from&#xD;
      fungal and viral infections are also removed in the T depletion process. CD45RA depletion has&#xD;
      been studied both as a single step to reduce the risk of GVHD, and also, in conjunction with&#xD;
      αβTCR depleted hematopoietic stem cell grafts to accelerate immune reconstitution. This is a&#xD;
      single institutional pilot trial of this T cell depletion technique. Patients with acute&#xD;
      leukemias at high risk for relapse are eligible to participate. Patients will be given CD45RA&#xD;
      depleted donor peripheral stem cells (PSCs) following T depleted hematopoietic stem cell&#xD;
      transplant (HSCT). A short course of GVHD prophylaxis will be used after CD45RA depletion.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 1, 2019</start_date>
  <completion_date type="Anticipated">January 2024</completion_date>
  <primary_completion_date type="Anticipated">January 2024</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of acute graft vs. host disease (GVHD)</measure>
    <time_frame>Up to 100 days post-transplantation</time_frame>
    <description>Incidence of acute graft vs. host disease (GVHD) (reaction of donor immune cells against host tissues)</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Acute Leukemia</condition>
  <condition>Acute Myeloid Leukemia</condition>
  <condition>Myelodysplastic Syndromes</condition>
  <condition>Acute Lymphoblastic Leukemia</condition>
  <condition>Mixed Lineage Leukemia</condition>
  <condition>Lymphoblastic Lymphoma</condition>
  <condition>Burkitt Lymphoma</condition>
  <condition>Juvenile Myelomonocytic Leukemia</condition>
  <arm_group>
    <arm_group_label>TBI regimen</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Standard of care myeloablative regimens will be used based on disease type and clinical status at time of transplant. Patients with acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma will receive total body irradiation (TBI) regimen (thiotepa, cyclophosphamide, TBI).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>TBI or busulfan regimen</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Standard of care myeloablative regimens will be used based on disease type and clinical status at time of transplant. Patients not diagnosed with ALL or lymphoblastic lymphoma may receive either total body irradiation (TBI) regimen (thiotepa, cyclophosphamide, TBI) or busulfan containing regimen (thiotepa, cyclophosphamide, busulfan).</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>CliniMACS Cell Processing System for TCRαβ + T Cell and CD45RA Depleted Peripheral Stem Cell Addback</intervention_name>
    <description>Peripheral stem cell (PSC) product will be processed using the CliniMACS device for TCRαβ and T cell depletion. Approximately 10% of the PSCs will undergo CD45RA depletion and cryopreservation. Patients will receive CD45RA depleted infusion after the TCRab PSCT.</description>
    <arm_group_label>TBI or busulfan regimen</arm_group_label>
    <arm_group_label>TBI regimen</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age: Patients &lt;25 years.&#xD;
&#xD;
          2. First allogeneic HSCT only.&#xD;
&#xD;
          3. Disease eligibility: Acute leukemias at high risk for relapse including positive&#xD;
             minimal residual disease at end consolidation, high risk cytogenetics, or relapse.&#xD;
             Hematologic malignancies including: acute myeloid leukemia, myelodysplastic syndromes,&#xD;
             acute lymphoblastic leukemia, mixed lineage or bi-phenotypic leukemia, lymphoblastic&#xD;
             or Burkitts, juvenile myelomonocytic leukemia&#xD;
&#xD;
          4. Evaluation of organ and infectious status as per our Bone Marrow Transplant standard&#xD;
             operating procedure (BMT SOP).&#xD;
&#xD;
          5. Signed consent by parent/guardian or able to give consent if &gt;18 years.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients who do not meet institutional disease, organ or infectious criteria&#xD;
&#xD;
          2. No suitable donor available for mobilized peripheral stem cells&#xD;
&#xD;
          3. Patients with genetic disorders including Fanconi anemia, Kostmann syndrome,&#xD;
             dyskeratosis congenital or other DNA repair defects.&#xD;
&#xD;
          4. Patients with Hodgkin lymphoma or non-Burkitts, non-lymphoblastic lymphoma&#xD;
&#xD;
        Donor selection and eligibility&#xD;
&#xD;
          1. Unrelated donor meets National Marrow Donor Program criteria for donation&#xD;
&#xD;
          2. HLA testing/matching&#xD;
&#xD;
          3. Donor must be willing to undergo granulocyte colony stimulating factor (GCSF)&#xD;
             mobilization and peripheral blood stem cell collection&#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>
    <phone>215-590-1303</phone>
    <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>Megan Atkinson</last_name>
      <email>atkinsonm@chop.edu</email>
    </contact>
    <contact_backup>
      <last_name>Barbara McGlynn</last_name>
      <email>mcglynn@chop.edu</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>January 16, 2019</study_first_submitted>
  <study_first_submitted_qc>January 16, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 18, 2019</study_first_posted>
  <last_update_submitted>February 20, 2023</last_update_submitted>
  <last_update_submitted_qc>February 20, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 21, 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>BMT Medical Director</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Burkitt Lymphoma</mesh_term>
    <mesh_term>Mycoses</mesh_term>
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</mesh_term>
    <mesh_term>Leukemia, Myelomonocytic, Juvenile</mesh_term>
    <mesh_term>Myelodysplastic 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/NCT03810196
org study id: 18-015286
nct id: NCT03810196
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
The major morbidities of allogeneic hematopoietic stem cell transplant with non-human
      leukocyte antigen (HLA) matched siblings are graft vs host disease (GVHD) and life
      threatening infections. T depletion of the donor hematopoietic stem cell graft is effective
      in preventing GVHD, but immune reconstitution is slow, increasing the risk of infections. An
      addback of donor CD45RA (naive T cells) depleted cells may improve immune reconstitution and
      help decrease the risk of infections.
The risk of severe graft versus host disease (GVHD) is increased with the use of unrelated
      and partially matched related donors. T cell depletion reduces the risk of severe GVHD, but
      immune reconstitution is delayed. Important memory T cells that may protect patients from
      fungal and viral infections are also removed in the T depletion process. CD45RA depletion has
      been studied both as a single step to reduce the risk of GVHD, and also, in conjunction with
      αβTCR depleted hematopoietic stem cell grafts to accelerate immune reconstitution. This is a
      single institutional pilot trial of this T cell depletion technique. Patients with acute
      leukemias at high risk for relapse are eligible to participate. Patients will be given CD45RA
      depleted donor peripheral stem cells (PSCs) following T depleted hematopoietic stem cell
      transplant (HSCT). A short course of GVHD prophylaxis will be used after CD45RA depletion.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of acute graft vs. host disease (GVHD)
time frame: Up to 100 days post-transplantation
description: Incidence of acute graft vs. host disease (GVHD) (reaction of donor immune cells against host tissues)
arm group label: TBI regimen
arm group type: Other
description: Standard of care myeloablative regimens will be used based on disease type and clinical status at time of transplant. Patients with acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma will receive total body irradiation (TBI) regimen (thiotepa, cyclophosphamide, TBI).
arm group label: TBI or busulfan regimen
arm group type: Other
description: Standard of care myeloablative regimens will be used based on disease type and clinical status at time of transplant. Patients not diagnosed with ALL or lymphoblastic lymphoma may receive either total body irradiation (TBI) regimen (thiotepa, cyclophosphamide, TBI) or busulfan containing regimen (thiotepa, cyclophosphamide, busulfan).
intervention type: Device
intervention name: CliniMACS Cell Processing System for TCRαβ + T Cell and CD45RA Depleted Peripheral Stem Cell Addback
description: Peripheral stem cell (PSC) product will be processed using the CliniMACS device for TCRαβ and T cell depletion. Approximately 10% of the PSCs will undergo CD45RA depletion and cryopreservation. Patients will receive CD45RA depleted infusion after the TCRab PSCT.
arm group label: TBI or busulfan regimen
arm group label: TBI 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
phone: 215-590-1303
email: MCGLYNN@chop.edu
facility: 
status: Recruiting
contact: 
contact backup: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Children's Hospital of Philadelphia
investigator full name: Nancy Bunin
investigator title: BMT Medical Director
mesh term: Burkitt Lymphoma
mesh term: Mycoses
mesh term: Lymphoma
mesh term: Leukemia
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Leukemia, Myelomonocytic, Juvenile
mesh term: Myelodysplastic Syndromes
sharing ipd: No