<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/NCT04409314</url>
  </required_header>
  <id_info>
    <org_study_id>20921</org_study_id>
    <secondary_id>NCI-2020-03216</secondary_id>
    <nct_id>NCT04409314</nct_id>
  </id_info>
  <brief_title>Hypoxia-Specific Imaging to Predict Outcomes of Chimeric Antigen Receptor T-cell Therapy</brief_title>
  <official_title>Pilot Study of Hypoxia-Specific Imaging to Predict Outcomes of Chimeric Antigen Receptor T-Cell Therapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, San Francisco</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of California, San Francisco</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study evaluates whether tumors present in patients with cancer who are planned to get&#xD;
      CAR T-cells have low amounts of oxygen (hypoxia). PET scans may be used to check the amounts&#xD;
      of oxygen within areas of cancer with a special radioactive tracer called FAZA that&#xD;
      specifically looks for areas of low oxygen. This study is being done to help researchers&#xD;
      determine how the amount of oxygen within areas of cancer affect how well CAR T-cells kill&#xD;
      cancer cells.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVE:&#xD;
&#xD;
      I. To evaluate the incidence of intratumoral hypoxia in patients with relapsed or refractory&#xD;
      (R/R) malignancies before treatment with chimeric antigen receptor (CAR) T-cell therapy.&#xD;
&#xD;
      SECONDARY OBJECTIVE:&#xD;
&#xD;
      I. To evaluate the association between intratumoral hypoxia and clinical responses to CAR&#xD;
      T-cell therapy.&#xD;
&#xD;
      EXPLORATORY OBJECTIVES:&#xD;
&#xD;
      I. To correlate intratumoral hypoxia with markers of CAR T-cell activity and toxicity.&#xD;
&#xD;
      2. To correlate pre-therapy fluorine F 18-fluoroazomycin arabinoside (18F-FAZA) uptake with&#xD;
      pre-therapy 18Ffluorodeoxyglucose (FDG) positron emission tomography (PET) uptake (if&#xD;
      available).&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Prior to CAR T-cell therapy, patients receive 18F-FAZA intravenously (IV). Beginning 2 hours&#xD;
      after injection, patients undergo a single PET scan. Patients are followed for up to 6 months&#xD;
      after CAR T-cell therapy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 16, 2020</start_date>
  <completion_date type="Actual">August 9, 2023</completion_date>
  <primary_completion_date type="Actual">August 9, 2023</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 fluorine F 18-fluoroazomycin arabinoside (18F-FAZA) positron emission tomography (PET) scans with positive hypoxic volume (HV)</measure>
    <time_frame>After completion of one-time 18F-FAZA PET scan, 1 day</time_frame>
    <description>Will calculate the uniformly minimum-variance unbiased estimator, p-value and 95% confidence interval (CI) for the response rates.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall response (OR)</measure>
    <time_frame>At 30, 90, and 180 days after chimeric antigen receptor (CAR) T-cell therapy, up to 6 months</time_frame>
    <description>Will determine OR at any time point as attainment of either complete response (CR) or partial response (PR). Logistic regressions will be used to evaluate the association between OR and intratumoral hypoxia, where hypoxia is analyzed as a binary and a continuous covariate.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Change in Mean Serum Ferritin levels</measure>
    <time_frame>Up to 6 months after CAR T-cell therapy</time_frame>
    <description>Will use descriptive statistical methods to present data, including frequencies/percentages for categorical variables and means, medians, standard deviations, and ranges for continuous variables. Will evaluate the effect of intratumoral hypoxia and other exploratory endpoints using chi-squared tests and logistic regressions for categorical variables and two-sample t-tests and linear regressions for continuous variables.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in Mean C-reactive protein (CRP) levels</measure>
    <time_frame>Up to 6 months after CAR T-cell therapy</time_frame>
    <description>Will use descriptive statistical methods to present data, including frequencies/percentages for categorical variables and means, medians, standard deviations, and ranges for continuous variables. Will evaluate the effect of intratumoral hypoxia and other exploratory endpoints using chi-squared tests and logistic regressions for categorical variables and two-sample t-tests and linear regressions for continuous variables.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in Mean Fibrinogen Levels</measure>
    <time_frame>Up to 6 months after CAR T-cell therapy</time_frame>
    <description>Will use descriptive statistical methods to present data, including frequencies/percentages for categorical variables and means, medians, standard deviations, and ranges for continuous variables. Will evaluate the effect of intratumoral hypoxia and other exploratory endpoints using chi-squared tests and logistic regressions for categorical variables and two-sample t-tests and linear regressions for continuous variables.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in Hepatic aminotransferase Levels</measure>
    <time_frame>Up to 6 months after CAR T-cell therapy</time_frame>
    <description>Will use descriptive statistical methods to present data, including frequencies/percentages for categorical variables and means, medians, standard deviations, and ranges for continuous variables. Will evaluate the effect of intratumoral hypoxia and other exploratory endpoints using chi-squared tests and logistic regressions for categorical variables and two-sample t-tests and linear regressions for continuous variables.</description>
  </other_outcome>
  <other_outcome>
    <measure>Incidence of cytokine release syndrome (CRS), neurotoxicity, or other adverse events (AEs) attributed to CAR T-cell therapy</measure>
    <time_frame>Up to 6 months after CAR T-cell therapy</time_frame>
    <description>Will use descriptive statistical methods to present data, including frequencies/percentages for categorical variables and means, medians, standard deviations, and ranges for continuous variables. Will evaluate the effect of intratumoral hypoxia and other exploratory endpoints using chi-squared tests and logistic regressions for categorical variables and two-sample t-tests and linear regressions for continuous variables.</description>
  </other_outcome>
  <other_outcome>
    <measure>Standardized uptake value maximum (SUVmax) calculations for tumor sites based on 18F-FAZA versus fludeoxyglucose F-18 (18F-FDG) uptake</measure>
    <time_frame>Up to 6 months after CAR T-cell therapy</time_frame>
    <description>Will use descriptive statistical methods to present data, including frequencies/percentages for categorical variables and means, medians, standard deviations, and ranges for continuous variables. Will evaluate the effect of intratumoral hypoxia and other exploratory endpoints using chi-squared tests and logistic regressions for categorical variables and two-sample t-tests and linear regressions for continuous variables.</description>
  </other_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">23</enrollment>
  <condition>Recurrent Aggressive Non-Hodgkin Lymphoma</condition>
  <condition>Recurrent Diffuse Large B-Cell Lymphoma</condition>
  <condition>Recurrent High Grade B-Cell Lymphoma</condition>
  <condition>Recurrent Malignant Neoplasm</condition>
  <condition>Recurrent Plasma Cell Myeloma</condition>
  <condition>Recurrent Primary Mediastinal (Thymic) Large B-Cell Cell Lymphoma</condition>
  <condition>Refractory Aggressive Non-Hodgkin Lymphoma</condition>
  <condition>Refractory Diffuse Large B-Cell Lymphoma</condition>
  <condition>Refractory High Grade B-Cell Lymphoma</condition>
  <condition>Refractory Malignant Neoplasm</condition>
  <condition>Refractory Plasma Cell Myeloma</condition>
  <condition>Refractory Primary Mediastinal (Thymic) Large B-Cell Cell Lymphoma</condition>
  <arm_group>
    <arm_group_label>Diagnostic (18F-FAZA PET scan)</arm_group_label>
    <description>Prior to CAR T-cell therapy, patients receive administration of 18F-FAZA IV. Patients will then undergo a vertex-thigh PET scan approximately 2 hours after injection of 18FFAZA lasting 30-45 minutes.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fluorine F 18-fluoroazomycin Arabinoside</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Diagnostic (18F-FAZA PET scan)</arm_group_label>
    <other_name>18F-FAZA</other_name>
    <other_name>18F-Fluoroazomycin Arabinoside</other_name>
    <other_name>FAZA F-18</other_name>
    <other_name>Fluoroazomycin Arabinoside F-18</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Positron Emission Tomography</intervention_name>
    <description>Undergo PET scan</description>
    <arm_group_label>Diagnostic (18F-FAZA PET scan)</arm_group_label>
    <other_name>Medical Imaging, Positron Emission Tomography</other_name>
    <other_name>PET</other_name>
    <other_name>PET Scan</other_name>
    <other_name>Positron Emission Tomography Scan</other_name>
    <other_name>Positron-Emission Tomography</other_name>
    <other_name>proton magnetic resonance spectroscopic imaging</other_name>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with relapsed or refractory malignancies who are planning to receive CAR T-cell&#xD;
        therapy at University of California, San Francisco (UCSF)&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically confirmed diagnosis of:&#xD;
&#xD;
               -  Aggressive lymphoma, including: Diffuse large B-cell lymphoma (DLBCL) (including&#xD;
                  transformed disease), high-grade B-cell lymphoma, or primary mediastinal B-cell&#xD;
                  lymphoma&#xD;
&#xD;
               -  Multiple myeloma (MM), with imaging within 6 months of enrollment demonstrating&#xD;
                  &gt;= 1 plasmacytoma measuring &gt;= 5 cm along any axis&#xD;
&#xD;
               -  Other malignancy with radiographically measurable disease&#xD;
&#xD;
          -  R/R disease with planned receipt of CAR T-cell therapy at University of California,&#xD;
             San Francisco (UCSF), either through an Food and Drug Administration-approved CAR&#xD;
             construct or through a separate interventional clinical trial&#xD;
&#xD;
          -  Ability to provide informed consent prior to study entry&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any serious and/or unstable pre-existing medical, psychiatric, or other condition that&#xD;
             could interfere with participant's safety, provision of informed consent, or&#xD;
             compliance with study procedures&#xD;
&#xD;
          -  Pregnancy or active lactation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>C. Babis Andreadis, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, San Francisco</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California, San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>May 26, 2020</study_first_submitted>
  <study_first_submitted_qc>May 26, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 1, 2020</study_first_posted>
  <last_update_submitted>August 17, 2023</last_update_submitted>
  <last_update_submitted_qc>August 17, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 21, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Multiple Myeloma</mesh_term>
    <mesh_term>Neoplasms, Plasma Cell</mesh_term>
    <mesh_term>Lymphoma, Non-Hodgkin</mesh_term>
    <mesh_term>Lymphoma, B-Cell</mesh_term>
    <mesh_term>Lymphoma, Large B-Cell, Diffuse</mesh_term>
    <mesh_term>Recurrence</mesh_term>
    <mesh_term>Hypoxia</mesh_term>
    <mesh_term>Aggression</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fluoroazomycin arabinoside</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/NCT04409314
org study id: 20921
secondary id: NCI-2020-03216
nct id: NCT04409314
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This study evaluates whether tumors present in patients with cancer who are planned to get
      CAR T-cells have low amounts of oxygen (hypoxia). PET scans may be used to check the amounts
      of oxygen within areas of cancer with a special radioactive tracer called FAZA that
      specifically looks for areas of low oxygen. This study is being done to help researchers
      determine how the amount of oxygen within areas of cancer affect how well CAR T-cells kill
      cancer cells.
PRIMARY OBJECTIVE:

      I. To evaluate the incidence of intratumoral hypoxia in patients with relapsed or refractory
      (R/R) malignancies before treatment with chimeric antigen receptor (CAR) T-cell therapy.

      SECONDARY OBJECTIVE:

      I. To evaluate the association between intratumoral hypoxia and clinical responses to CAR
      T-cell therapy.

      EXPLORATORY OBJECTIVES:

      I. To correlate intratumoral hypoxia with markers of CAR T-cell activity and toxicity.

      2. To correlate pre-therapy fluorine F 18-fluoroazomycin arabinoside (18F-FAZA) uptake with
      pre-therapy 18Ffluorodeoxyglucose (FDG) positron emission tomography (PET) uptake (if
      available).

      OUTLINE:

      Prior to CAR T-cell therapy, patients receive 18F-FAZA intravenously (IV). Beginning 2 hours
      after injection, patients undergo a single PET scan. Patients are followed for up to 6 months
      after CAR T-cell therapy.
observational model: Cohort
time perspective: Prospective
measure: Proportion of fluorine F 18-fluoroazomycin arabinoside (18F-FAZA) positron emission tomography (PET) scans with positive hypoxic volume (HV)
time frame: After completion of one-time 18F-FAZA PET scan, 1 day
description: Will calculate the uniformly minimum-variance unbiased estimator, p-value and 95% confidence interval (CI) for the response rates.
measure: Overall response (OR)
time frame: At 30, 90, and 180 days after chimeric antigen receptor (CAR) T-cell therapy, up to 6 months
description: Will determine OR at any time point as attainment of either complete response (CR) or partial response (PR). Logistic regressions will be used to evaluate the association between OR and intratumoral hypoxia, where hypoxia is analyzed as a binary and a continuous covariate.
measure: Change in Mean Serum Ferritin levels
time frame: Up to 6 months after CAR T-cell therapy
description: Will use descriptive statistical methods to present data, including frequencies/percentages for categorical variables and means, medians, standard deviations, and ranges for continuous variables. Will evaluate the effect of intratumoral hypoxia and other exploratory endpoints using chi-squared tests and logistic regressions for categorical variables and two-sample t-tests and linear regressions for continuous variables.
measure: Change in Mean C-reactive protein (CRP) levels
time frame: Up to 6 months after CAR T-cell therapy
description: Will use descriptive statistical methods to present data, including frequencies/percentages for categorical variables and means, medians, standard deviations, and ranges for continuous variables. Will evaluate the effect of intratumoral hypoxia and other exploratory endpoints using chi-squared tests and logistic regressions for categorical variables and two-sample t-tests and linear regressions for continuous variables.
measure: Change in Mean Fibrinogen Levels
time frame: Up to 6 months after CAR T-cell therapy
description: Will use descriptive statistical methods to present data, including frequencies/percentages for categorical variables and means, medians, standard deviations, and ranges for continuous variables. Will evaluate the effect of intratumoral hypoxia and other exploratory endpoints using chi-squared tests and logistic regressions for categorical variables and two-sample t-tests and linear regressions for continuous variables.
measure: Change in Hepatic aminotransferase Levels
time frame: Up to 6 months after CAR T-cell therapy
description: Will use descriptive statistical methods to present data, including frequencies/percentages for categorical variables and means, medians, standard deviations, and ranges for continuous variables. Will evaluate the effect of intratumoral hypoxia and other exploratory endpoints using chi-squared tests and logistic regressions for categorical variables and two-sample t-tests and linear regressions for continuous variables.
measure: Incidence of cytokine release syndrome (CRS), neurotoxicity, or other adverse events (AEs) attributed to CAR T-cell therapy
time frame: Up to 6 months after CAR T-cell therapy
description: Will use descriptive statistical methods to present data, including frequencies/percentages for categorical variables and means, medians, standard deviations, and ranges for continuous variables. Will evaluate the effect of intratumoral hypoxia and other exploratory endpoints using chi-squared tests and logistic regressions for categorical variables and two-sample t-tests and linear regressions for continuous variables.
measure: Standardized uptake value maximum (SUVmax) calculations for tumor sites based on 18F-FAZA versus fludeoxyglucose F-18 (18F-FDG) uptake
time frame: Up to 6 months after CAR T-cell therapy
description: Will use descriptive statistical methods to present data, including frequencies/percentages for categorical variables and means, medians, standard deviations, and ranges for continuous variables. Will evaluate the effect of intratumoral hypoxia and other exploratory endpoints using chi-squared tests and logistic regressions for categorical variables and two-sample t-tests and linear regressions for continuous variables.
arm group label: Diagnostic (18F-FAZA PET scan)
description: Prior to CAR T-cell therapy, patients receive administration of 18F-FAZA IV. Patients will then undergo a vertex-thigh PET scan approximately 2 hours after injection of 18FFAZA lasting 30-45 minutes.
intervention type: Drug
intervention name: Fluorine F 18-fluoroazomycin Arabinoside
description: Given IV
arm group label: Diagnostic (18F-FAZA PET scan)
other name: 18F-FAZA
other name: 18F-Fluoroazomycin Arabinoside
other name: FAZA F-18
other name: Fluoroazomycin Arabinoside F-18
intervention type: Procedure
intervention name: Positron Emission Tomography
description: Undergo PET scan
arm group label: Diagnostic (18F-FAZA PET scan)
other name: Medical Imaging, Positron Emission Tomography
other name: PET
other name: PET Scan
other name: Positron Emission Tomography Scan
other name: Positron-Emission Tomography
other name: proton magnetic resonance spectroscopic imaging
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: C. Babis Andreadis, MD
role: Principal Investigator
affiliation: University of California, San Francisco
facility: 
country: United States
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Neoplasms
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Lymphoma, Non-Hodgkin
mesh term: Lymphoma, B-Cell
mesh term: Lymphoma, Large B-Cell, Diffuse
mesh term: Recurrence
mesh term: Hypoxia
mesh term: Aggression
mesh term: Fluoroazomycin arabinoside
sharing ipd: No