<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/NCT04483778</url>
  </required_header>
  <id_info>
    <org_study_id>STRIvE-02</org_study_id>
    <nct_id>NCT04483778</nct_id>
  </id_info>
  <brief_title>B7H3 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults</brief_title>
  <official_title>Phase I Study of B7H3 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Seattle Children's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Seattle Children's Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a phase I, open-label, non-randomized study that will enroll pediatric and young&#xD;
      adult research participants with relapsed or refractory non-CNS solid tumors to evaluate the&#xD;
      safety, feasibility, and efficacy of administering T cell products derived from the research&#xD;
      participant's blood that have been genetically modified to express a B7H3-specific receptor&#xD;
      (chimeric antigen receptor, or CAR) that will target and kill solid tumors that express B7H3.&#xD;
      On Arm A of the study, research participants will receive B7H3-specific CAR T cells only. On&#xD;
      Arm B of the study, research participants will receive CAR T cells directed at B7H3 and CD19,&#xD;
      a marker on the surface of B lymphocytes, following the hypothesis that CD19+ B cells serving&#xD;
      in their normal role as antigen presenting cells to T cells will promote the expansion and&#xD;
      persistence of the CAR T cells. Arm A CAR T cells include the protein EGFRt and Arm B CAR T&#xD;
      cells include the protein HER2tG. These proteins can be used to both track and destroy the&#xD;
      CAR T cells in case of undue toxicity. The primary objectives of the study will be to&#xD;
      determine the feasibility of manufacturing the cell products, the safety of the T cell&#xD;
      product infusion, to determine the maximum tolerated dose of the CAR T cells products, to&#xD;
      describe the full toxicity profile of each product, and determine the persistence of the&#xD;
      modified cell in the participant's body on each arm. Participants will receive a single dose&#xD;
      of T cells comprised of two different subtypes of T cells (CD4 and CD8 T cells) felt to&#xD;
      benefit one another once administered to the research participants for improved potential&#xD;
      therapeutic effect. The secondary objectives of this protocol are to study the number of&#xD;
      modified cells in the patients and the duration they continue to be at detectable levels. The&#xD;
      investigators will also quantitate anti-tumor efficacy on each arm. Participants who&#xD;
      experience significant and potentially life-threatening toxicities (other than clinically&#xD;
      manageable toxicities related to T cells working, called cytokine release syndrome) will&#xD;
      receive infusions of cetuximab (an antibody commercially available that targets EGFRt) or&#xD;
      trastuzumab (an antibody commercially available that targets HER2tG) to assess the ability of&#xD;
      the EGFRt on the T cells to be an effective suicide mechanism for the elimination of the&#xD;
      transferred T cell products.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">July 13, 2020</start_date>
  <completion_date type="Anticipated">December 2040</completion_date>
  <primary_completion_date type="Anticipated">December 2025</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Assess the safety and tolerability of cellular immunotherapy utilizing ex-vivo expanded autologous T cells genetically modified to express B7H3-specific CAR (Arm A)</measure>
    <time_frame>28 days</time_frame>
    <description>Type, frequency, severity, and duration of adverse events will be tabulated and summarized</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Assess the safety and tolerability of cellular immunotherapy utilizing ex-vivo expanded autologous T cells genetically modified to express a bispecific B7H3xCD19 CAR (Arm B)</measure>
    <time_frame>28 days</time_frame>
    <description>Type, frequency, severity, and duration of adverse events will be tabulated and summarized</description>
  </primary_outcome>
  <primary_outcome>
    <measure>To assess the safety and tolerability of cellular immunotherapy utilizing ex-vivo expanded autologous T cells genetically modified to express a bispecific B7H3xCD19 CAR given in combination with pembrolizumab (Arm C)</measure>
    <time_frame>28 days</time_frame>
    <description>Type, frequency, severity, and duration of adverse events will be tabulated and summarized to determine maximal tolerated dose</description>
  </primary_outcome>
  <primary_outcome>
    <measure>To determine the maximum tolerated dose (MTD) of B7H3-specific CAR (Arm A)</measure>
    <time_frame>28 days</time_frame>
    <description>Type, frequency, severity, and duration of adverse events will be tabulated and summarized to determine maximal tolerated dose</description>
  </primary_outcome>
  <primary_outcome>
    <measure>To determine the maximum tolerated dose of bispecific B7H3xCD19 CAR (Arm B)</measure>
    <time_frame>28 days</time_frame>
    <description>Type, frequency, severity, and duration of adverse events will be tabulated and summarized</description>
  </primary_outcome>
  <primary_outcome>
    <measure>To determine the feasibility of administration of pembrolizumab in combination with bispecific B7H3xCD19 CAR (Arm C)</measure>
    <time_frame>28 days</time_frame>
    <description>Type, frequency, severity, and duration of adverse events will be tabulated and summarized</description>
  </primary_outcome>
  <primary_outcome>
    <measure>To assess the dose limiting toxicities (DLTs) and describe the full toxicity profile for each study arm</measure>
    <time_frame>28 days</time_frame>
    <description>Type, frequency, severity, and duration of adverse events will be tabulated and summarized</description>
  </primary_outcome>
  <primary_outcome>
    <measure>To assess the feasibility of manufacturing B7H3 specific CARs from patient-derived lymphocytes</measure>
    <time_frame>28 days</time_frame>
    <description>Type, frequency, severity, and duration of adverse events will be tabulated and summarized</description>
  </primary_outcome>
  <primary_outcome>
    <measure>To assess the feasibility of manufacturing B7H3xCD19 bispecific CARs from patient-derived lymphocytes</measure>
    <time_frame>28 days</time_frame>
    <description>Type, frequency, severity, and duration of adverse events will be tabulated and summarized</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Determine the duration of in vivo persistence of adoptively transferred T cells in the peripheral blood and compare engraftment between T cell products and treatment arms</measure>
    <time_frame>84 days</time_frame>
    <description>Presence of CAR T cells in the peripheral blood will be assessed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determine the magnitude of in vivo persistence of adoptively transferred T cells in the peripheral blood and compare engraftment between T cell products</measure>
    <time_frame>84 days</time_frame>
    <description>Number of CAR T cells in the peripheral blood will be assessed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quantitate anti-tumor responses by measuring changes in tumor burden using disease-specific evaluations</measure>
    <time_frame>84 days</time_frame>
    <description>Presence of CAR T cells in the peripheral blood will be assessed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Describe the relative expansion and persistence of the CAR T cell product and retention of function for B7H3xCD19 bispecific CARs determined by maintenance of B cell aplasia (BCA) with and without pembrolizumab</measure>
    <time_frame>84 days</time_frame>
    <description>Presence of CAR T cells in the peripheral blood will be assessed</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Evaluate for the presence of B7H3 CAR T cells in tumor tissue and/or normal tissue if a tissue biopsy, tumor biopsy, or resection is clinically indicated post-treatment</measure>
    <time_frame>84 days</time_frame>
    <description>Tumor tissue, when obtained, will be assessed for the presence of adoptively transferred CAR T cells</description>
  </other_outcome>
  <other_outcome>
    <measure>Evaluate B7H3 antigen expression in tumor tissue and/or normal tissue if a tissue biopsy, tumor biopsy, or resection is available</measure>
    <time_frame>84 days</time_frame>
    <description>Tumor tissue, when obtained, will be assessed for the presence of B7H3 antigen</description>
  </other_outcome>
  <other_outcome>
    <measure>Analyze blood, bone marrow, CSF, normal tissue, and/or tumor tissue for biomarkers of safety and/or anti-tumor activity</measure>
    <time_frame>84 days</time_frame>
    <description>If a tissue biopsy, tumor biopsy, or resection is clinically indicated post-treatment, pathology will be assessed for the presence of B7H3 CAR T cells</description>
  </other_outcome>
  <other_outcome>
    <measure>Assess the efficacy of infusional cetuximab and/or trastuzumab in ablating transferred T cells and ameliorating acute toxicities in treated participants</measure>
    <time_frame>84 days</time_frame>
    <description>Biologic specimens, when obtained, will be assessed for biomarkers of safety and/or anti-tumor efficacy</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">68</enrollment>
  <condition>Pediatric Solid Tumor</condition>
  <condition>Germ Cell Tumor</condition>
  <condition>Retinoblastoma</condition>
  <condition>Hepatoblastoma</condition>
  <condition>Wilms Tumor</condition>
  <condition>Rhabdoid Tumor</condition>
  <condition>Carcinoma</condition>
  <condition>Osteosarcoma</condition>
  <condition>Ewing Sarcoma</condition>
  <condition>Rhabdomyosarcoma</condition>
  <condition>Synovial Sarcoma</condition>
  <condition>Clear Cell Sarcoma</condition>
  <condition>Malignant Peripheral Nerve Sheath Tumors</condition>
  <condition>Desmoplastic Small Round Cell Tumor</condition>
  <condition>Soft Tissue Sarcoma</condition>
  <condition>Neuroblastoma</condition>
  <condition>Melanoma</condition>
  <arm_group>
    <arm_group_label>SCRI-CARB7H3(s)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Autologous CD4+ and CD8+ T-cells genetically modified to express an B7H3-specific CAR</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SCRI-CARB7H3(s)x19</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Autologous CD4+ and CD8+ T-cells genetically modified to a bispecific B7H3xCD19 CAR</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SCRI-CARB7H3(s)x19 plus pembrolizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Autologous CD4+ and CD8+ T-cells genetically modified to express a bispecific B7H3xCD19 CAR given in combination with pembrolizumab</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>second generation 4-1BBζ B7H3-EGFRt-DHFR</intervention_name>
    <description>Autologous CD4+ and CD8+ T-cells lentivirally transduced to express a second generation 4-1BBζ B7H3-EGFRt-DHFR</description>
    <arm_group_label>SCRI-CARB7H3(s)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>second generation 4-1BBζ B7H3-EGFRt-DHFR(selected) and a second generation 4-1BBζ CD19-Her2tG</intervention_name>
    <description>Autologous CD4+ and CD8+ T-cells lentivirally transduced to express a second generation 4-1BBζ B7H3-EGFRt-DHFR(selected) and a second generation 4-1BBζ CD19-Her2tG</description>
    <arm_group_label>SCRI-CARB7H3(s)x19</arm_group_label>
    <arm_group_label>SCRI-CARB7H3(s)x19 plus pembrolizumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>SCRI-CARB7H3(s)x19 plus pembrolizumab</description>
    <arm_group_label>SCRI-CARB7H3(s)x19 plus pembrolizumab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participants age ≤ 26 years at the time of consent for study participation; the first&#xD;
             2 participants enrolled and treated with CAR T cells in both Arms A and B will be ≥ 15&#xD;
             years. and ≤ 26 years at time of consent for study participation&#xD;
&#xD;
          -  Histologically diagnosed malignant, non-primary CNS solid tumor&#xD;
&#xD;
          -  Evidence of refractory or recurrent disease&#xD;
&#xD;
          -  Lansky or Karnofsky score ≥ 50&#xD;
&#xD;
          -  Life expectancy ≥ 8 weeks&#xD;
&#xD;
          -  Recovered from significant acute toxic effects of all prior chemotherapy,&#xD;
             immunotherapy and radiotherapy&#xD;
&#xD;
          -  If no apheresis product or usable T cell product is available, all chemotherapy has&#xD;
             been discontinued ≥ 7 days prior to enrollment&#xD;
&#xD;
          -  If no apheresis or usable T cell product is available, all biologic therapy has been&#xD;
             discontinued ≥ 7 days prior to enrollment&#xD;
&#xD;
          -  If no apheresis product or T cell product is available, all systemic corticosteroid&#xD;
             therapy has been discontinued ≥ 7 days prior to enrollment (physiologic replacement&#xD;
             dosing is allowed)&#xD;
&#xD;
          -  If no apheresis product or usable T cell product is available, at least 3 half-lives&#xD;
             or 30 days (whichever is shorter) from time of last dose of anti-tumor directed&#xD;
             antibody therapy (including checkpoint inhibitor) at time of enrollment&#xD;
&#xD;
          -  If no apheresis product or usable T cell product is available, at least 6 weeks post&#xD;
             last dose of myeloablative therapy and autologous and/or allogeneic stem cell&#xD;
             transplant, or non-myeloablative therapy and allogeneic stem cell transplant (all&#xD;
             timed from stem cell infusion). Participants who receive autologous stem cell infusion&#xD;
             following non-myeloablative therapy are eligible once all other eligibility&#xD;
             requirements are met.&#xD;
&#xD;
          -  If no apheresis product or usable T cell product is available, participants who have&#xD;
             received genetically modified cell therapy must be at least 30 days from most recent&#xD;
             cell infusion prior to enrollment&#xD;
&#xD;
          -  If no apheresis product or usable T cell product is available, participants with&#xD;
             neuroblastoma must be at least 12 weeks from I131 MIBG therapy.&#xD;
&#xD;
          -  Adequate organ function&#xD;
&#xD;
          -  Adequate laboratory values&#xD;
&#xD;
          -  Participant is able to tolerate apheresis (including placement of temporary apheresis&#xD;
             catheter, if necessary), or already has an apheresis product available for use in&#xD;
             manufacturing.&#xD;
&#xD;
          -  Participants of childbearing potential must agree to use highly effective&#xD;
             contraception&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Presence of active malignancy other than primary malignant solid tumor diagnosis&#xD;
&#xD;
          -  Current relevant CNS pathology&#xD;
&#xD;
          -  Receiving external beam radiation therapy at time of enrollment&#xD;
&#xD;
          -  Presence of active GVHD, or receiving immunosuppressive therapy for treatment or&#xD;
             prevention of GVHD within 4 weeks prior to enrollment&#xD;
&#xD;
          -  Participant is pregnant or breastfeeding&#xD;
&#xD;
          -  Participant has presence of active severe infection&#xD;
&#xD;
          -  Participant has presence of any condition that, in the option of an investigator,&#xD;
             would prohibit the participant from undergoing treatment under this protocol&#xD;
&#xD;
          -  Participant has primary immunodeficiency syndrome&#xD;
&#xD;
          -  Unwilling or unable to provide consent/assent for participation in the study and 15&#xD;
             year follow up period&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>0 Years</minimum_age>
    <maximum_age>26 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Navin Pinto, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Seattle Children's Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Seattle Children's Hospital</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>July 14, 2020</study_first_submitted>
  <study_first_submitted_qc>July 20, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 23, 2020</study_first_posted>
  <last_update_submitted>July 6, 2023</last_update_submitted>
  <last_update_submitted_qc>July 6, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 10, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Seattle Children's Hospital</investigator_affiliation>
    <investigator_full_name>Colleen Annesley</investigator_full_name>
    <investigator_title>Medical Director, Seattle Children's Therapeutics</investigator_title>
  </responsible_party>
  <keyword>CAR T cell</keyword>
  <keyword>Pediatric</keyword>
  <keyword>Young adults</keyword>
  <keyword>Non-CNS solid tumor</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Sarcoma</mesh_term>
    <mesh_term>Neuroblastoma</mesh_term>
    <mesh_term>Osteosarcoma</mesh_term>
    <mesh_term>Rhabdomyosarcoma</mesh_term>
    <mesh_term>Sarcoma, Ewing</mesh_term>
    <mesh_term>Wilms Tumor</mesh_term>
    <mesh_term>Retinoblastoma</mesh_term>
    <mesh_term>Rhabdoid Tumor</mesh_term>
    <mesh_term>Sarcoma, Synovial</mesh_term>
    <mesh_term>Hepatoblastoma</mesh_term>
    <mesh_term>Nerve Sheath Neoplasms</mesh_term>
    <mesh_term>Neurofibrosarcoma</mesh_term>
    <mesh_term>Desmoplastic Small Round Cell Tumor</mesh_term>
    <mesh_term>Sarcoma, Clear Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pembrolizumab</mesh_term>
  </intervention_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/NCT04483778
org study id: STRIvE-02
nct id: NCT04483778
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a phase I, open-label, non-randomized study that will enroll pediatric and young
      adult research participants with relapsed or refractory non-CNS solid tumors to evaluate the
      safety, feasibility, and efficacy of administering T cell products derived from the research
      participant's blood that have been genetically modified to express a B7H3-specific receptor
      (chimeric antigen receptor, or CAR) that will target and kill solid tumors that express B7H3.
      On Arm A of the study, research participants will receive B7H3-specific CAR T cells only. On
      Arm B of the study, research participants will receive CAR T cells directed at B7H3 and CD19,
      a marker on the surface of B lymphocytes, following the hypothesis that CD19+ B cells serving
      in their normal role as antigen presenting cells to T cells will promote the expansion and
      persistence of the CAR T cells. Arm A CAR T cells include the protein EGFRt and Arm B CAR T
      cells include the protein HER2tG. These proteins can be used to both track and destroy the
      CAR T cells in case of undue toxicity. The primary objectives of the study will be to
      determine the feasibility of manufacturing the cell products, the safety of the T cell
      product infusion, to determine the maximum tolerated dose of the CAR T cells products, to
      describe the full toxicity profile of each product, and determine the persistence of the
      modified cell in the participant's body on each arm. Participants will receive a single dose
      of T cells comprised of two different subtypes of T cells (CD4 and CD8 T cells) felt to
      benefit one another once administered to the research participants for improved potential
      therapeutic effect. The secondary objectives of this protocol are to study the number of
      modified cells in the patients and the duration they continue to be at detectable levels. The
      investigators will also quantitate anti-tumor efficacy on each arm. Participants who
      experience significant and potentially life-threatening toxicities (other than clinically
      manageable toxicities related to T cells working, called cytokine release syndrome) will
      receive infusions of cetuximab (an antibody commercially available that targets EGFRt) or
      trastuzumab (an antibody commercially available that targets HER2tG) to assess the ability of
      the EGFRt on the T cells to be an effective suicide mechanism for the elimination of the
      transferred T cell products.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Assess the safety and tolerability of cellular immunotherapy utilizing ex-vivo expanded autologous T cells genetically modified to express B7H3-specific CAR (Arm A)
time frame: 28 days
description: Type, frequency, severity, and duration of adverse events will be tabulated and summarized
measure: Assess the safety and tolerability of cellular immunotherapy utilizing ex-vivo expanded autologous T cells genetically modified to express a bispecific B7H3xCD19 CAR (Arm B)
time frame: 28 days
description: Type, frequency, severity, and duration of adverse events will be tabulated and summarized
measure: To assess the safety and tolerability of cellular immunotherapy utilizing ex-vivo expanded autologous T cells genetically modified to express a bispecific B7H3xCD19 CAR given in combination with pembrolizumab (Arm C)
time frame: 28 days
description: Type, frequency, severity, and duration of adverse events will be tabulated and summarized to determine maximal tolerated dose
measure: To determine the maximum tolerated dose (MTD) of B7H3-specific CAR (Arm A)
time frame: 28 days
description: Type, frequency, severity, and duration of adverse events will be tabulated and summarized to determine maximal tolerated dose
measure: To determine the maximum tolerated dose of bispecific B7H3xCD19 CAR (Arm B)
time frame: 28 days
description: Type, frequency, severity, and duration of adverse events will be tabulated and summarized
measure: To determine the feasibility of administration of pembrolizumab in combination with bispecific B7H3xCD19 CAR (Arm C)
time frame: 28 days
description: Type, frequency, severity, and duration of adverse events will be tabulated and summarized
measure: To assess the dose limiting toxicities (DLTs) and describe the full toxicity profile for each study arm
time frame: 28 days
description: Type, frequency, severity, and duration of adverse events will be tabulated and summarized
measure: To assess the feasibility of manufacturing B7H3 specific CARs from patient-derived lymphocytes
time frame: 28 days
description: Type, frequency, severity, and duration of adverse events will be tabulated and summarized
measure: To assess the feasibility of manufacturing B7H3xCD19 bispecific CARs from patient-derived lymphocytes
time frame: 28 days
description: Type, frequency, severity, and duration of adverse events will be tabulated and summarized
measure: Determine the duration of in vivo persistence of adoptively transferred T cells in the peripheral blood and compare engraftment between T cell products and treatment arms
time frame: 84 days
description: Presence of CAR T cells in the peripheral blood will be assessed
measure: Determine the magnitude of in vivo persistence of adoptively transferred T cells in the peripheral blood and compare engraftment between T cell products
time frame: 84 days
description: Number of CAR T cells in the peripheral blood will be assessed
measure: Quantitate anti-tumor responses by measuring changes in tumor burden using disease-specific evaluations
time frame: 84 days
description: Presence of CAR T cells in the peripheral blood will be assessed
measure: Describe the relative expansion and persistence of the CAR T cell product and retention of function for B7H3xCD19 bispecific CARs determined by maintenance of B cell aplasia (BCA) with and without pembrolizumab
time frame: 84 days
description: Presence of CAR T cells in the peripheral blood will be assessed
measure: Evaluate for the presence of B7H3 CAR T cells in tumor tissue and/or normal tissue if a tissue biopsy, tumor biopsy, or resection is clinically indicated post-treatment
time frame: 84 days
description: Tumor tissue, when obtained, will be assessed for the presence of adoptively transferred CAR T cells
measure: Evaluate B7H3 antigen expression in tumor tissue and/or normal tissue if a tissue biopsy, tumor biopsy, or resection is available
time frame: 84 days
description: Tumor tissue, when obtained, will be assessed for the presence of B7H3 antigen
measure: Analyze blood, bone marrow, CSF, normal tissue, and/or tumor tissue for biomarkers of safety and/or anti-tumor activity
time frame: 84 days
description: If a tissue biopsy, tumor biopsy, or resection is clinically indicated post-treatment, pathology will be assessed for the presence of B7H3 CAR T cells
measure: Assess the efficacy of infusional cetuximab and/or trastuzumab in ablating transferred T cells and ameliorating acute toxicities in treated participants
time frame: 84 days
description: Biologic specimens, when obtained, will be assessed for biomarkers of safety and/or anti-tumor efficacy
arm group label: SCRI-CARB7H3(s)
arm group type: Experimental
description: Autologous CD4+ and CD8+ T-cells genetically modified to express an B7H3-specific CAR
arm group label: SCRI-CARB7H3(s)x19
arm group type: Experimental
description: Autologous CD4+ and CD8+ T-cells genetically modified to a bispecific B7H3xCD19 CAR
arm group label: SCRI-CARB7H3(s)x19 plus pembrolizumab
arm group type: Experimental
description: Autologous CD4+ and CD8+ T-cells genetically modified to express a bispecific B7H3xCD19 CAR given in combination with pembrolizumab
intervention type: Biological
intervention name: second generation 4-1BBζ B7H3-EGFRt-DHFR
description: Autologous CD4+ and CD8+ T-cells lentivirally transduced to express a second generation 4-1BBζ B7H3-EGFRt-DHFR
arm group label: SCRI-CARB7H3(s)
intervention type: Biological
intervention name: second generation 4-1BBζ B7H3-EGFRt-DHFR(selected) and a second generation 4-1BBζ CD19-Her2tG
description: Autologous CD4+ and CD8+ T-cells lentivirally transduced to express a second generation 4-1BBζ B7H3-EGFRt-DHFR(selected) and a second generation 4-1BBζ CD19-Her2tG
arm group label: SCRI-CARB7H3(s)x19
arm group label: SCRI-CARB7H3(s)x19 plus pembrolizumab
intervention type: Drug
intervention name: Pembrolizumab
description: SCRI-CARB7H3(s)x19 plus pembrolizumab
arm group label: SCRI-CARB7H3(s)x19 plus pembrolizumab
criteria: 
gender: All
minimum age: 0 Years
maximum age: 26 Years
healthy volunteers: No
last name: Navin Pinto, MD
role: Principal Investigator
affiliation: Seattle Children's Hospital
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Seattle Children's Hospital
investigator full name: Colleen Annesley
investigator title: Medical Director, Seattle Children's Therapeutics
mesh term: Neoplasms
mesh term: Sarcoma
mesh term: Neuroblastoma
mesh term: Osteosarcoma
mesh term: Rhabdomyosarcoma
mesh term: Sarcoma, Ewing
mesh term: Wilms Tumor
mesh term: Retinoblastoma
mesh term: Rhabdoid Tumor
mesh term: Sarcoma, Synovial
mesh term: Hepatoblastoma
mesh term: Nerve Sheath Neoplasms
mesh term: Neurofibrosarcoma
mesh term: Desmoplastic Small Round Cell Tumor
mesh term: Sarcoma, Clear Cell
mesh term: Pembrolizumab
sharing ipd: No