<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/NCT03827343</url>
  </required_header>
  <id_info>
    <org_study_id>999919044</org_study_id>
    <secondary_id>19-C-N044</secondary_id>
    <nct_id>NCT03827343</nct_id>
  </id_info>
  <brief_title>Retrospective Study of Immunotherapy Related Toxicities and Factors Impacting Outcomes in Children and Adults With Cancer</brief_title>
  <official_title>Retrospective Study of Immunotherapy Related Toxicities and Factors Impacting Outcomes in Children and Adults With Cancer</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>
      Immunotherapy is changing the landscape of cancer therapy. Particularly unique to&#xD;
      immunotherapy is the toxicity profile, which differs from chemotherapy-based strategies and&#xD;
      can be associated with inflammatory responses and/or autoimmune type reactions resulting from&#xD;
      activation of the immune system. Referred to as immune related adverse events (irAEs), these&#xD;
      adverse events may require systemic immunosuppression or have other consequences and present&#xD;
      unique management challenges. Specific to CAR T-cell and other adoptive cell therapies is the&#xD;
      constellation of symptoms referred to as cytokine release syndrome (CRS), which can range in&#xD;
      severity from mild to severe, and can require both cytokine directed blockade and/or systemic&#xD;
      immunosuppression to ameliorate the side effects. While side effects may be unique to each&#xD;
      individual immunotherapy, and may also be patient specific, cumulative experience will help&#xD;
      to inform toxicity profiles and improve management of side effects and overall outcomes.&#xD;
&#xD;
      Given the number of immunotherapeutic approaches at the NCI, the primary goal of this&#xD;
      protocol is to facilitate retrospective chart review of various immunotherapy trials at the&#xD;
      NCI used in the treatment of cancer to comprehensively study toxicity profiles. This study&#xD;
      will not involve the use of specimens or participant contact. All data that is needed has&#xD;
      already been collected on the individual treatment protocols and is available in CRIS records&#xD;
      or protocol specific databases.&#xD;
&#xD;
      Data will only be collected from treatment protocols where the PI has given permission for&#xD;
      use of the data on the trial the subject was enrolled on. This protocol will be amended to&#xD;
      incorporate new research objectives and new protocols as necessary....&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Immunotherapy is changing the landscape of cancer therapy. Particularly unique to&#xD;
      immunotherapy is the toxicity profile, which differs from chemotherapy-based strategies and&#xD;
      can be associated with inflammatory responses and/or autoimmune type reactions resulting from&#xD;
      activation of the immune system. Referred to as immune related adverse events (irAEs), these&#xD;
      adverse events may require systemic immunosuppression or have other consequences and present&#xD;
      unique management challenges. Specific to CAR T-cell and other adoptive cell therapies is the&#xD;
      constellation of symptoms referred to as cytokine release syndrome (CRS), which can range in&#xD;
      severity from mild to severe, and can require both cytokine directed blockade and/or systemic&#xD;
      immunosuppression to ameliorate the side effects. While side effects may be unique to each&#xD;
      individual immunotherapy, and may also be patient specific, cumulative experience will help&#xD;
      to inform toxicity profiles and improve management of side effects and overall outcomes.&#xD;
&#xD;
      Given the number of immunotherapeutic approaches at the NCI, the primary goal of this&#xD;
      protocol is to facilitate retrospective chart review of various immunotherapy trials at the&#xD;
      NCI used in the treatment of cancer to comprehensively study toxicity profiles. This study&#xD;
      will not involve the use of specimens or participant contact. All data that is needed has&#xD;
      already been collected on the individual treatment protocols and is available in CRIS records&#xD;
      or protocol specific databases. Data will only be collected from treatment protocols where&#xD;
      the PI has given permission for use of the data on the trial the subject was enrolled on or&#xD;
      from standard of care protocols. This protocol will be amended to incorporate new research&#xD;
      objectives and new protocols as necessary.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 23, 2019</start_date>
  <completion_date type="Anticipated">December 31, 2025</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>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>To develop a retrospective study to allow for comparison of immunotherapy related toxicity profiles and risk factors across a set of protocols in the NCI.</measure>
    <time_frame>2 years</time_frame>
    <description>Summary of immunotherapy related toxicity profiles and risk factors across a set of protocols in the NCI.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Evaluate infectious complications and their risk factors in patients who receive CAR-T cell therapy for cancer</measure>
    <time_frame>2 years</time_frame>
    <description>Summary of infectious complications and their risk factors in patients who receive CAR-T cell therapy for cancer</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate the incidence, risk factors for, and treatment of HLH/MAS in patients who receive CAR-T cell therapy</measure>
    <time_frame>2 years</time_frame>
    <description>Incidence and risk factors for, and treatment of HLH/MAS in patients who receive CAR-T cell therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence and time to resolution</measure>
    <time_frame>2 years</time_frame>
    <description>Incidence of and time to resolution of grade 3 and 4 cytopenias post-CAR T-cell therapy in those who achieve a complete remission.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall and relapse free survival</measure>
    <time_frame>2 years</time_frame>
    <description>Summary of overall and relapse free survival and transplant associated toxicities for patients undergoing HSCT following CAR-T cell therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of end organ toxicities</measure>
    <time_frame>2 years</time_frame>
    <description>Incidence of grade 3 and 4 end organ toxicities experienced within the first 30 days of CAR T-cell therapy and includes associations between pre-CAR organ function as well as post-CAR response to such toxicities as well as validate the CAR-Comorbidity Index as predictive model of CRS severity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate response and toxicity profile of second CAR T-cell infusions</measure>
    <time_frame>2 years</time_frame>
    <description>Summary of factors associated with response to second CAR T-cell infusion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate impact of race/ethnicity and obesity on CAR T-cell outcomes</measure>
    <time_frame>2 years</time_frame>
    <description>Summary of response and toxicity profiles in patients based on race/ethnicity and also in those who are obese compared to those who are not.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate impact of cryopreservation on outcomes following CAR T-cell infusion</measure>
    <time_frame>2 years</time_frame>
    <description>Summary of cryopreservation and patients' outcomes following CAR T-cell infusion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate outcomes for patients with ALL and Down Syndrome following CAR T-cell therapy</measure>
    <time_frame>2 years</time_frame>
    <description>Summary of outcomes of patients with ALL and Down Syndrome who have received CAR T-cell therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate absolute lymphocyte count following lymphodepleting chemotherapy</measure>
    <time_frame>2 years</time_frame>
    <description>Summary of absolute lymphocyte count across lymphodepleting regimens</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate relationship between clinical variable and apheresis and manufacturing products</measure>
    <time_frame>2 years</time_frame>
    <description>Summary of clinical variables and apheresis and manufacturing products</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate incidence of hypertension, identify risk factors for development of hypertension, summarize medical management in CAR setting, and identify complications</measure>
    <time_frame>2 years</time_frame>
    <description>Summary of incidence of hypertension, risk factors, medical management and complications</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Describe baseline demographics, prior treatment characteristics and outcomes based on patients who are referred to CAR T-cell program</measure>
    <time_frame>2 years</time_frame>
    <description>Summary of demographics, prior treatment and outcomes for patients referred to CAR T-cell program</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of pre-infusion BCA and use of BCA as a prognostic marker for CAR T-cell associated toxicity and efficacy</measure>
    <time_frame>2 years</time_frame>
    <description>Incidence of BCA pre-infusion and use as a prognostic marker for CAR T-cell associated toxicity and efficacy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Presence and durability of CD72 expression in both B-ALL and normal B-ALL/hematogones</measure>
    <time_frame>2 years</time_frame>
    <description>Summary of CD72 expression in both B-ALL and normal B-ALL/hematogones and evaluate use as prognostic marker for CAR T-cell associated toxicity and efficacy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate interventions, documentation of care goals, and use of palliative care consultation or other symptom management</measure>
    <time_frame>2 years</time_frame>
    <description>Summary of interventions, documentation of care goals, and use of palliative care consultation or other symptom management for patients treated with CAR T-cell therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate long-term outcomes of survivors who received CAR T-cell therapy</measure>
    <time_frame>2 years</time_frame>
    <description>Summary of long-term outcomes of survivors who received CAR T-cell therapy</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">500</enrollment>
  <condition>Macrophage Activation Syndrome</condition>
  <condition>Primary Hemophagocytic Lymphohistiocytosis</condition>
  <arm_group>
    <arm_group_label>1</arm_group_label>
    <description>Retrospective chart review of children and adults with cancer enrolled on immunotherapy treatment protocols in the NCI.</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Children and adults with cancer enrolled on immunotherapy treatment protocols in the NCI.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        -  Retrospective chart review of various immunotherapy trials at the NCI used in the&#xD;
             treatment of cancer to comprehensively study toxicity profiles. This study will not&#xD;
             involve the use of specimens or participant contact. All data that is needed has&#xD;
             already been collected on the individual treatment protocols and is available in CRIS&#xD;
             records or protocol specific databases.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Month</minimum_age>
    <maximum_age>120 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>
  <location>
    <facility>
      <name>National Cancer Institute (NCI)</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20892</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 13, 2023</verification_date>
  <study_first_submitted>January 31, 2019</study_first_submitted>
  <study_first_submitted_qc>January 31, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 1, 2019</study_first_posted>
  <last_update_submitted>September 15, 2023</last_update_submitted>
  <last_update_submitted_qc>September 15, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>CAR-T Cell Therapy</keyword>
  <keyword>Macrophage Activation Syndrome (MAS)</keyword>
  <keyword>Hemophagocytic Lymphohistiocytosis (HLH)</keyword>
  <keyword>Natural History</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphohistiocytosis, Hemophagocytic</mesh_term>
    <mesh_term>Macrophage Activation Syndrome</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.</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 available during the study and indefinitely.</ipd_time_frame>
    <ipd_access_criteria>Clinical data will be made available via subscription to BTRIS and with the permission of the study PI.</ipd_access_criteria>
  </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/NCT03827343
org study id: 999919044
secondary id: 19-C-N044
nct id: NCT03827343
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Immunotherapy is changing the landscape of cancer therapy. Particularly unique to
      immunotherapy is the toxicity profile, which differs from chemotherapy-based strategies and
      can be associated with inflammatory responses and/or autoimmune type reactions resulting from
      activation of the immune system. Referred to as immune related adverse events (irAEs), these
      adverse events may require systemic immunosuppression or have other consequences and present
      unique management challenges. Specific to CAR T-cell and other adoptive cell therapies is the
      constellation of symptoms referred to as cytokine release syndrome (CRS), which can range in
      severity from mild to severe, and can require both cytokine directed blockade and/or systemic
      immunosuppression to ameliorate the side effects. While side effects may be unique to each
      individual immunotherapy, and may also be patient specific, cumulative experience will help
      to inform toxicity profiles and improve management of side effects and overall outcomes.

      Given the number of immunotherapeutic approaches at the NCI, the primary goal of this
      protocol is to facilitate retrospective chart review of various immunotherapy trials at the
      NCI used in the treatment of cancer to comprehensively study toxicity profiles. This study
      will not involve the use of specimens or participant contact. All data that is needed has
      already been collected on the individual treatment protocols and is available in CRIS records
      or protocol specific databases.

      Data will only be collected from treatment protocols where the PI has given permission for
      use of the data on the trial the subject was enrolled on. This protocol will be amended to
      incorporate new research objectives and new protocols as necessary....
Immunotherapy is changing the landscape of cancer therapy. Particularly unique to
      immunotherapy is the toxicity profile, which differs from chemotherapy-based strategies and
      can be associated with inflammatory responses and/or autoimmune type reactions resulting from
      activation of the immune system. Referred to as immune related adverse events (irAEs), these
      adverse events may require systemic immunosuppression or have other consequences and present
      unique management challenges. Specific to CAR T-cell and other adoptive cell therapies is the
      constellation of symptoms referred to as cytokine release syndrome (CRS), which can range in
      severity from mild to severe, and can require both cytokine directed blockade and/or systemic
      immunosuppression to ameliorate the side effects. While side effects may be unique to each
      individual immunotherapy, and may also be patient specific, cumulative experience will help
      to inform toxicity profiles and improve management of side effects and overall outcomes.

      Given the number of immunotherapeutic approaches at the NCI, the primary goal of this
      protocol is to facilitate retrospective chart review of various immunotherapy trials at the
      NCI used in the treatment of cancer to comprehensively study toxicity profiles. This study
      will not involve the use of specimens or participant contact. All data that is needed has
      already been collected on the individual treatment protocols and is available in CRIS records
      or protocol specific databases. Data will only be collected from treatment protocols where
      the PI has given permission for use of the data on the trial the subject was enrolled on or
      from standard of care protocols. This protocol will be amended to incorporate new research
      objectives and new protocols as necessary.
observational model: Cohort
time perspective: Retrospective
measure: To develop a retrospective study to allow for comparison of immunotherapy related toxicity profiles and risk factors across a set of protocols in the NCI.
time frame: 2 years
description: Summary of immunotherapy related toxicity profiles and risk factors across a set of protocols in the NCI.
measure: Evaluate infectious complications and their risk factors in patients who receive CAR-T cell therapy for cancer
time frame: 2 years
description: Summary of infectious complications and their risk factors in patients who receive CAR-T cell therapy for cancer
measure: Evaluate the incidence, risk factors for, and treatment of HLH/MAS in patients who receive CAR-T cell therapy
time frame: 2 years
description: Incidence and risk factors for, and treatment of HLH/MAS in patients who receive CAR-T cell therapy
measure: Incidence and time to resolution
time frame: 2 years
description: Incidence of and time to resolution of grade 3 and 4 cytopenias post-CAR T-cell therapy in those who achieve a complete remission.
measure: Overall and relapse free survival
time frame: 2 years
description: Summary of overall and relapse free survival and transplant associated toxicities for patients undergoing HSCT following CAR-T cell therapy
measure: Incidence of end organ toxicities
time frame: 2 years
description: Incidence of grade 3 and 4 end organ toxicities experienced within the first 30 days of CAR T-cell therapy and includes associations between pre-CAR organ function as well as post-CAR response to such toxicities as well as validate the CAR-Comorbidity Index as predictive model of CRS severity
measure: Evaluate response and toxicity profile of second CAR T-cell infusions
time frame: 2 years
description: Summary of factors associated with response to second CAR T-cell infusion
measure: Evaluate impact of race/ethnicity and obesity on CAR T-cell outcomes
time frame: 2 years
description: Summary of response and toxicity profiles in patients based on race/ethnicity and also in those who are obese compared to those who are not.
measure: Evaluate impact of cryopreservation on outcomes following CAR T-cell infusion
time frame: 2 years
description: Summary of cryopreservation and patients' outcomes following CAR T-cell infusion
measure: Evaluate outcomes for patients with ALL and Down Syndrome following CAR T-cell therapy
time frame: 2 years
description: Summary of outcomes of patients with ALL and Down Syndrome who have received CAR T-cell therapy
measure: Evaluate absolute lymphocyte count following lymphodepleting chemotherapy
time frame: 2 years
description: Summary of absolute lymphocyte count across lymphodepleting regimens
measure: Evaluate relationship between clinical variable and apheresis and manufacturing products
time frame: 2 years
description: Summary of clinical variables and apheresis and manufacturing products
measure: Evaluate incidence of hypertension, identify risk factors for development of hypertension, summarize medical management in CAR setting, and identify complications
time frame: 2 years
description: Summary of incidence of hypertension, risk factors, medical management and complications
measure: Describe baseline demographics, prior treatment characteristics and outcomes based on patients who are referred to CAR T-cell program
time frame: 2 years
description: Summary of demographics, prior treatment and outcomes for patients referred to CAR T-cell program
measure: Incidence of pre-infusion BCA and use of BCA as a prognostic marker for CAR T-cell associated toxicity and efficacy
time frame: 2 years
description: Incidence of BCA pre-infusion and use as a prognostic marker for CAR T-cell associated toxicity and efficacy
measure: Presence and durability of CD72 expression in both B-ALL and normal B-ALL/hematogones
time frame: 2 years
description: Summary of CD72 expression in both B-ALL and normal B-ALL/hematogones and evaluate use as prognostic marker for CAR T-cell associated toxicity and efficacy
measure: Evaluate interventions, documentation of care goals, and use of palliative care consultation or other symptom management
time frame: 2 years
description: Summary of interventions, documentation of care goals, and use of palliative care consultation or other symptom management for patients treated with CAR T-cell therapy
measure: Evaluate long-term outcomes of survivors who received CAR T-cell therapy
time frame: 2 years
description: Summary of long-term outcomes of survivors who received CAR T-cell therapy
arm group label: 1
description: Retrospective chart review of children and adults with cancer enrolled on immunotherapy treatment protocols in the NCI.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 1 Month
maximum age: 120 Years
healthy volunteers: No
last name: Nirali N Shah, M.D.
role: Principal Investigator
affiliation: National Cancer Institute (NCI)
facility: 
country: United States
responsible party type: Sponsor
mesh term: Lymphohistiocytosis, Hemophagocytic
mesh term: Macrophage Activation Syndrome
sharing ipd: Yes
ipd description: .All IPD recorded in the medical record will be shared with intramural investigators upon request.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd time frame: Clinical data available during the study and indefinitely.
ipd access criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI.