xml: <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/NCT05969002</url>
    </required_header>
    <id_info>
      <org_study_id>10001620</org_study_id>
      <secondary_id>001620-C</secondary_id>
      <nct_id>NCT05969002</nct_id>
    </id_info>
    <brief_title>Pilot Prospective Study for PET-CT Imaging in Participants With Relapsed/Refractory Acute Leukemias</brief_title>
    <official_title>Pilot Prospective Study for PET-CT Imaging in Participants With Relapsed/Refractory Acute Leukemias</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>National Cancer Institute (NCI)</agency>
        <agency_class>NIH</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>National Institutes of Health Clinical Center (CC)</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Background&#xD;
  &#xD;
        Acute lymphoblastic leukemia (ALL) accounts for about 25% of childhood cancers and for about&#xD;
        20% of adult leukemias. The disease can be treated with CAR T-cell infusion but non-central&#xD;
        nervous system (CNS) extramedullary disease (EMD) is associated with lower rates of complete&#xD;
        remission. 18-fludeoxyglucose (18F-FDG) positron emission tomography-computed tomography&#xD;
        (PET-CT) has been shown to be effective for detection of non-CNS EMD in ALL. Pre and post CAR&#xD;
        T-cell infusion may help to predict outcomes and risk of early progression.&#xD;
  &#xD;
        Objectives&#xD;
  &#xD;
        To describe the number of adults with relapsed/refractory B-cell ALL who proceed to CAR&#xD;
        T-cell therapy.&#xD;
  &#xD;
        Eligibility&#xD;
  &#xD;
        Participants &gt;=18 years with relapsed/refractory B-cell ALL who are being screened for CAR&#xD;
        T-cell clinical trial enrollment, and&#xD;
  &#xD;
        Participants &lt;18 with relapsed/refractory B cell ALL who are being screened for CAR T-cell&#xD;
        clinical trial enrollment and have a clinical indication for FDG PET-CT prior to CAR&#xD;
        infusion.&#xD;
  &#xD;
        Design&#xD;
  &#xD;
        Pilot study to add screening FDG PET-CT as part of the pre-CAR T-cell baseline evaluation&#xD;
        with additional imaging at day 28 and future timepoints pending evidence of non-CNS EMD on&#xD;
        initial scan....&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Background&#xD;
  &#xD;
          -  Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy, accounting&#xD;
             for approximately 25% of all childhood cancer. ALL also spans the age spectrum and&#xD;
             represents approximately 20% of adult leukemias.&#xD;
  &#xD;
          -  Despite improved survival rates for pediatric, adolescent, and adult ALL, relapse&#xD;
             following upfront therapy is common. The recent introduction of chimeric antigen&#xD;
             receptor (CAR) T-cell therapies has improved outcomes compared to other available&#xD;
             salvage regimens, but limitations to its efficacy exist.&#xD;
  &#xD;
          -  The presence of non-central nervous system (CNS) extramedullary disease (EMD) at the&#xD;
             time of CAR T-cell infusion is associated with lower complete remission (CR) rates&#xD;
             compared to isolated medullary disease even with evidence of CAR trafficking to EMD&#xD;
             sites. Despite implications for CAR therapy, the true incidence of non-CNS EMD for&#xD;
             patients proceeding to CAR is unknown. Our retrospective study estimates the EMD rate to&#xD;
             be as high as 21%.&#xD;
  &#xD;
          -  Although 18-fludeoxyglucose (18F-FDG) positron emission tomography-computed tomography&#xD;
             (PET-CT) is feasible and has been shown to be high yield for detection of non-CNS EMD in&#xD;
             ALL, it is not part of standard evaluation pre-CAR T-cell therapy.&#xD;
  &#xD;
          -  Recent studies examining the use of pre and post-infusion FDG PET-CT in patients with&#xD;
             large cell lymphoma treated with CAR have shown Deauville response criteria, total&#xD;
             metabolic tumor volume, and change of standardized uptake values (SUV) to be predictive&#xD;
             of CAR T outcomes and risk of early progression. In addition to the use of PET-CT in&#xD;
             monitoring CAR T response, circulating tumor DNA (ctDNA) has been shown risk stratify&#xD;
             and predict outcomes in large cell lymphoma and can be detected prior to radiographic&#xD;
             evidence of relapse.&#xD;
  &#xD;
        Objectives&#xD;
  &#xD;
        -Describe the proportion of non-CNS EMD in adult participants with relapsed/refractory BALL&#xD;
        proceeding to CAR T-cell therapy&#xD;
  &#xD;
        Eligibility&#xD;
  &#xD;
          -  Participants &gt;=18 years with relapsed/refractory B cell ALL who are being screened for&#xD;
             CAR T-cell clinical trial enrollment, and&#xD;
  &#xD;
          -  Participants &lt;18 with relapsed/refractory B cell ALL who are being screened for CAR&#xD;
             T-cell clinical trial enrollment and have a clinical indication for FDG PET-CT prior to&#xD;
             CAR infusion.&#xD;
  &#xD;
        Design&#xD;
  &#xD;
        -Pilot study to add screening FDG PET-CT as part of the pre-CAR T-cell baseline evaluation&#xD;
        with additional imaging at day 28 and future timepoints pending evidence of non-CNS EMD on&#xD;
        initial scan.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">August 25, 2023</start_date>
    <completion_date type="Anticipated">April 30, 2026</completion_date>
    <primary_completion_date type="Anticipated">December 31, 2025</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>Proportion of non-CNS EMD in adult participants with relapsed/refractory B-ALL proceeding to CAR T-cell therapy</measure>
      <time_frame>3 months</time_frame>
      <description>Estimate the fraction of adult participants who are PET positive for non-CNS EMD</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Correlation of bone marrow CAR T-cell response by flow cytometry with ctDNA</measure>
      <time_frame>day 28</time_frame>
      <description>Bone marrow response by flow cytometry with ctDNA</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Determine proportion of non-CNS EMD with concurrent CNS disease or history of CNS disease</measure>
      <time_frame>At time of LP</time_frame>
      <description>Incidence of concurrent CNS disease with non-CNS EMD.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Identify risk factors associated with presence of non-CNS EMD pre-CAR</measure>
      <time_frame>through 3 months post CAR T</time_frame>
      <description>Risk factors associated with presence of non-CNS EMD</description>
    </secondary_outcome>
    <number_of_groups>2</number_of_groups>
    <enrollment type="Anticipated">36</enrollment>
    <condition>B Cell</condition>
    <condition>Acute Lymphoblastic Leukemia</condition>
    <condition>Relapsed/Refractory</condition>
    <arm_group>
      <arm_group_label>Adult</arm_group_label>
      <description>Participants &gt;/=18 years old with relapsed/refractory B cell ALL proceeding to CAR therapy at the NIH</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Pediatric</arm_group_label>
      <description>Participants &lt;18 proceeding to CAR therapy at the NIH with a clinical indication for FDG PET-CT prior to CAR infusion</description>
    </arm_group>
    <eligibility>
      <study_pop>
        <textblock>
          Primary care clinic&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          -  INCLUSION CRITERIA:&#xD;
  &#xD;
            -  Diagnosis: Participants must have a B cell ALL (inclusive of CML with ALL&#xD;
               transformation)&#xD;
  &#xD;
            -  Age: 5-39 years&#xD;
  &#xD;
                 -  All participants &gt;=18 years old with relapsed/refractory B cell ALL potentially&#xD;
                    proceeding to CAR therapy at the NIH, or&#xD;
  &#xD;
                 -  Any participant &lt;18 potentially proceeding to CAR therapy at the NIH with a&#xD;
                    clinical indication for FDG PET-CT prior to CAR infusion:&#xD;
  &#xD;
                      -  History of prior EMD&#xD;
  &#xD;
                      -  History of post-HSCT relapse&#xD;
  &#xD;
                      -  Clinical signs or incidental findings suspicious for EMD&#xD;
  &#xD;
                      -  Peripheral disease out of proportion of bone marrow disease burden&#xD;
  &#xD;
            -  Participants who are breastfeeding or plan to breastfeed must agree to&#xD;
               discontinue/postpone breastfeeding within 24 hours of any PET-CT scan&#xD;
  &#xD;
            -  Ability and willingness of participant or Legally Authorized Representative (LAR) to&#xD;
               coenroll on protocol 10-C-0086 &quot;Comprehensive Omics Analysis of Pediatric Solid Tumors&#xD;
               and Establishment of a Repository for Related Biological Studies&quot;.&#xD;
  &#xD;
            -  Ability of participant or Legally Authorized Representative (LAR) to understand and&#xD;
               the willingness to sign a written informed consent document.&#xD;
  &#xD;
          EXCLUSION CRITERIA:&#xD;
  &#xD;
            -  Pregnant women are excluded from this study&#xD;
  &#xD;
            -  History of severe, immediate hypersensitivity reaction attributed to compounds of&#xD;
               similar chemical or biologic composition to any agents used in study (e.g., FDG&#xD;
               injection)&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>5 Years</minimum_age>
      <maximum_age>39 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Nirali N Shah, M.D.</last_name>
      <role>Principal Investigator</role>
      <affiliation>National Cancer Institute (NCI)</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>NCI Pediatric Leukemia, Lymphoma Transpl</last_name>
      <phone>(240) 760-6970</phone>
      <email>ncilltct@mail.nih.gov</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Nirali N Shah, M.D.</last_name>
      <phone>(240) 760-6970</phone>
      <email>shahnn@mail.nih.gov</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>National Institutes of Health Clinical Center</name>
        <address>
          <city>Bethesda</city>
          <state>Maryland</state>
          <zip>20892</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>National Cancer Institute Referral Office</last_name>
        <phone>888-624-1937</phone>
      </contact>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <link>
      <url>https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_001620-C.html</url>
      <description>NIH Clinical Center Detailed Web Page</description>
    </link>
    <verification_date>September 6, 2023</verification_date>
    <study_first_submitted>July 31, 2023</study_first_submitted>
    <study_first_submitted_qc>July 31, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 1, 2023</study_first_posted>
    <last_update_submitted>September 7, 2023</last_update_submitted>
    <last_update_submitted_qc>September 7, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 8, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Imaging</keyword>
    <keyword>Natural History</keyword>
    <keyword>ACUTE LEUKEMIA</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Leukemia</mesh_term>
      <mesh_term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>.All IPD recorded in the medical record will be shared with intramural investigators upon request. In addition, all large scale genomic sequencing will be shared with subscribers to dbGAP.</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
      <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
      <ipd_time_frame>Clinical data will be made available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active.</ipd_time_frame>
      <ipd_access_criteria>Clinical data will be made available upon request and with the permission of the study PI. Genomic data are made available via dbGAP through requests to the data custodians.</ipd_access_criteria>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05969002
  org study id: 10001620
  secondary id: 001620-C
  nct id: NCT05969002
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  Background
  
        Acute lymphoblastic leukemia (ALL) accounts for about 25% of childhood cancers and for about
        20% of adult leukemias. The disease can be treated with CAR T-cell infusion but non-central
        nervous system (CNS) extramedullary disease (EMD) is associated with lower rates of complete
        remission. 18-fludeoxyglucose (18F-FDG) positron emission tomography-computed tomography
        (PET-CT) has been shown to be effective for detection of non-CNS EMD in ALL. Pre and post CAR
        T-cell infusion may help to predict outcomes and risk of early progression.
  
        Objectives
  
        To describe the number of adults with relapsed/refractory B-cell ALL who proceed to CAR
        T-cell therapy.
  
        Eligibility
  
        Participants >=18 years with relapsed/refractory B-cell ALL who are being screened for CAR
        T-cell clinical trial enrollment, and
  
        Participants <18 with relapsed/refractory B cell ALL who are being screened for CAR T-cell
        clinical trial enrollment and have a clinical indication for FDG PET-CT prior to CAR
        infusion.
  
        Design
  
        Pilot study to add screening FDG PET-CT as part of the pre-CAR T-cell baseline evaluation
        with additional imaging at day 28 and future timepoints pending evidence of non-CNS EMD on
        initial scan....
  Background
  
          -  Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy, accounting
             for approximately 25% of all childhood cancer. ALL also spans the age spectrum and
             represents approximately 20% of adult leukemias.
  
          -  Despite improved survival rates for pediatric, adolescent, and adult ALL, relapse
             following upfront therapy is common. The recent introduction of chimeric antigen
             receptor (CAR) T-cell therapies has improved outcomes compared to other available
             salvage regimens, but limitations to its efficacy exist.
  
          -  The presence of non-central nervous system (CNS) extramedullary disease (EMD) at the
             time of CAR T-cell infusion is associated with lower complete remission (CR) rates
             compared to isolated medullary disease even with evidence of CAR trafficking to EMD
             sites. Despite implications for CAR therapy, the true incidence of non-CNS EMD for
             patients proceeding to CAR is unknown. Our retrospective study estimates the EMD rate to
             be as high as 21%.
  
          -  Although 18-fludeoxyglucose (18F-FDG) positron emission tomography-computed tomography
             (PET-CT) is feasible and has been shown to be high yield for detection of non-CNS EMD in
             ALL, it is not part of standard evaluation pre-CAR T-cell therapy.
  
          -  Recent studies examining the use of pre and post-infusion FDG PET-CT in patients with
             large cell lymphoma treated with CAR have shown Deauville response criteria, total
             metabolic tumor volume, and change of standardized uptake values (SUV) to be predictive
             of CAR T outcomes and risk of early progression. In addition to the use of PET-CT in
             monitoring CAR T response, circulating tumor DNA (ctDNA) has been shown risk stratify
             and predict outcomes in large cell lymphoma and can be detected prior to radiographic
             evidence of relapse.
  
        Objectives
  
        -Describe the proportion of non-CNS EMD in adult participants with relapsed/refractory BALL
        proceeding to CAR T-cell therapy
  
        Eligibility
  
          -  Participants >=18 years with relapsed/refractory B cell ALL who are being screened for
             CAR T-cell clinical trial enrollment, and
  
          -  Participants <18 with relapsed/refractory B cell ALL who are being screened for CAR
             T-cell clinical trial enrollment and have a clinical indication for FDG PET-CT prior to
             CAR infusion.
  
        Design
  
        -Pilot study to add screening FDG PET-CT as part of the pre-CAR T-cell baseline evaluation
        with additional imaging at day 28 and future timepoints pending evidence of non-CNS EMD on
        initial scan.
  observational model: Cohort
  time perspective: Prospective
  measure: Proportion of non-CNS EMD in adult participants with relapsed/refractory B-ALL proceeding to CAR T-cell therapy
  time frame: 3 months
  description: Estimate the fraction of adult participants who are PET positive for non-CNS EMD
  measure: Correlation of bone marrow CAR T-cell response by flow cytometry with ctDNA
  time frame: day 28
  description: Bone marrow response by flow cytometry with ctDNA
  measure: Determine proportion of non-CNS EMD with concurrent CNS disease or history of CNS disease
  time frame: At time of LP
  description: Incidence of concurrent CNS disease with non-CNS EMD.
  measure: Identify risk factors associated with presence of non-CNS EMD pre-CAR
  time frame: through 3 months post CAR T
  description: Risk factors associated with presence of non-CNS EMD
  arm group label: Adult
  description: Participants >/=18 years old with relapsed/refractory B cell ALL proceeding to CAR therapy at the NIH
  arm group label: Pediatric
  description: Participants <18 proceeding to CAR therapy at the NIH with a clinical indication for FDG PET-CT prior to CAR infusion
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 5 Years
  maximum age: 39 Years
  healthy volunteers: No
  last name: Nirali N Shah, M.D.
  role: Principal Investigator
  affiliation: National Cancer Institute (NCI)
  last name: NCI Pediatric Leukemia, Lymphoma Transpl
  phone: (240) 760-6970
  email: ncilltct@mail.nih.gov
  last name: Nirali N Shah, M.D.
  phone: (240) 760-6970
  email: shahnn@mail.nih.gov
  facility: 
  status: Recruiting
  contact: 
  country: United States
  url: https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_001620-C.html
  description: NIH Clinical Center Detailed Web Page
  responsible party type: Sponsor
  mesh term: Leukemia
  mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
  sharing ipd: Yes
  ipd description: .All IPD recorded in the medical record will be shared with intramural investigators upon request. In addition, all large scale genomic sequencing will be shared with subscribers to dbGAP.
  ipd info type: Study Protocol
  ipd info type: Statistical Analysis Plan (SAP)
  ipd info type: Informed Consent Form (ICF)
  ipd time frame: Clinical data will be made available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active.
  ipd access criteria: Clinical data will be made available upon request and with the permission of the study PI. Genomic data are made available via dbGAP through requests to the data custodians.