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/NCT05993949</url>
    </required_header>
    <id_info>
      <org_study_id>IRB-68603</org_study_id>
      <nct_id>NCT05993949</nct_id>
    </id_info>
    <brief_title>Study of Brexucabtagene Autoleucel Plus Dasatinib in Adults With Acute Lymphoblastic Leukemia</brief_title>
    <official_title>Phase 1b Study of Brexucabtagene Autoleucel Plus Dasatinib in Adults With Acute Lymphoblastic Leukemia</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Stanford University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Kite Pharma</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Stanford University</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>
        To assess the feasibility of oral dasatinib pulses (3 consecutive days per week) during the&#xD;
        first month following infusion of brexucabtagene autoleucel (Tecartus) in adults with&#xD;
        relapsed or refractory B-cell acute lymphoblastic leukemia.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 15, 2023</start_date>
    <completion_date type="Anticipated">August 2025</completion_date>
    <primary_completion_date type="Anticipated">August 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>Single Group Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Feasibility of dasatinib pulses</measure>
      <time_frame>1 month</time_frame>
      <description>Feasibility of administering oral dasatinib pulses (3 consecutive doses per week) during the first month following Tecartus infusion. Feasibility will be defined as the ability of 8 out of 20 subjects to miss no more than one cycle (defined as one week of at least three consecutive days of dasatinib) within the first month following Tecartus infusion.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Safety of oral dasatinib pulses</measure>
      <time_frame>2 years</time_frame>
      <description>Defined by a description of adverse events and serious adverse events at least possibly related to dasatinib following CAR T cell therapy; it will include an analysis of the sequential toxicity boundaries in that the analysis does not lead to a pause in the study; further defined as no reports of suspected death on study.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall response rate</measure>
      <time_frame>3 months</time_frame>
      <description>The definitions for response are primarily based on the standardized response criteria defined by National Comprehensive Cancer Network (NCCN) Guidelines (NCCN, 2021 v.2).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Complete Response (CR)</measure>
      <time_frame>3 months</time_frame>
      <description>The definitions for response are primarily based on the standardized response criteria defined by National Comprehensive Cancer Network (NCCN) Guidelines (NCCN, 2021 v.2).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>MRD-negative Complete Response (CR)</measure>
      <time_frame>3 months</time_frame>
      <description>The definitions for response are primarily based on the standardized response criteria defined by National Comprehensive Cancer Network (NCCN) Guidelines (NCCN, 2021 v.2).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of CR in responders</measure>
      <time_frame>2 years</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progression Free Survival (PFS) following Tecartus plus dasatinib</measure>
      <time_frame>2 years</time_frame>
      <description>PFS is defined as the time from the start of the investigational therapy to the date of radiographic progression</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall Survival (OS) following Tecartus plus dasatinib</measure>
      <time_frame>2 years</time_frame>
      <description>OS is defined as the time from the date of initial disease diagnosis to the date of death from any cause</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">20</enrollment>
    <condition>Lymphoblastic Leukemia</condition>
    <arm_group>
      <arm_group_label>Dasatinib</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Oral dasatinib 100mg</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Dasatinib</intervention_name>
      <description>3 pulses of oral dasatinib (100 mg daily) beginning on Day 4 (+up to 2 days) for 3 days (with 4 days off), repeated weekly. The weekly 3-day pulse schedule of dasatinib may continue for up to 3 months in subjects who continue to meet the dasatinib eligibility criteria and who do not meet off treatment/off study criteria</description>
      <arm_group_label>Dasatinib</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Relapsed or refractory B-precursor ALL defined as one of the following:&#xD;
  &#xD;
                 -  Primary refractory disease (&gt;=5% blasts or persistent extramedullary disease&#xD;
                    following induction therapy)&#xD;
  &#xD;
                 -  First or later relapse of marrow or extramedullary disease&#xD;
  &#xD;
                 -  Persistence of MRD defined as detectable ALL by flow cytometry, PCR, or&#xD;
                    next-generation sequencing&#xD;
  &#xD;
                 -  Relapsed or refractory disease after allogeneic transplant provided individual is&#xD;
                    at least 100 days from transplant at time of enrollment&#xD;
  &#xD;
                 -  Patients with isolated, asymptomatic CNS relapse will be eligible&#xD;
  &#xD;
                      -  Age &gt;=18 years&#xD;
  &#xD;
                      -  Eastern cooperative oncology group (ECOG) performance status of 0-2&#xD;
  &#xD;
                      -  Adequate renal, hepatic, pulmonary and cardiac function defined as:&#xD;
  &#xD;
                 -  Creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 cc/min&#xD;
  &#xD;
                 -  Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 2.5 x&#xD;
                    upper limit of normal (ULN)&#xD;
  &#xD;
                 -  Total bilirubin ≤ 1.5 mg/dl, except in individuals with Gilbert's syndrome.&#xD;
  &#xD;
                 -  Cardiac ejection fraction ≥ 50%, no evidence of clinically significant&#xD;
                    pericardial effusion, and no clinically significant arrhythmias&#xD;
  &#xD;
                 -  Baseline oxygen saturation &gt; 92% on room air&#xD;
  &#xD;
                 -  QTc ≤ 500ms&#xD;
  &#xD;
                      -  In individuals previously treated with blinatumomab, CD19 tumor expression&#xD;
                         in bone marrow or peripheral blood by flow cytometry or extramedullary site&#xD;
                         by IHC or flow cytometry&#xD;
  &#xD;
                      -  Negative serum or urine beta-HCG test in females of childbearing potential&#xD;
                         within 3 weeks of enrollment&#xD;
  &#xD;
                      -  Subjects of childbearing or child fathering potential must be willing to&#xD;
                         practice birth control from the time of enrollment on this study Page 10 of&#xD;
                         83 Version 1.0 dated 27-April-2023 and for six (6) months after receiving&#xD;
                         the preparative conditioning regimen.&#xD;
  &#xD;
                      -  Must be able to give informed consent. Legal authorized representative (LAR)&#xD;
                         is permitted if subject is cognitively able to provide verbal assent.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  History of dasatinib intolerance&#xD;
  &#xD;
            -  Known sensitivity or allergy to aminoglycosides or any agents/reagents used in this&#xD;
               study&#xD;
  &#xD;
            -  Blast count &gt; 75% in the bone marrow.&#xD;
  &#xD;
            -  History of malignancy other than non-melanoma skin cancer or carcinoma in situ (e.g.&#xD;
               cervix, bladder, breast) unless disease free for at least 2 years&#xD;
  &#xD;
            -  Presence of CNS-3 disease with neurological changes&#xD;
  &#xD;
            -  History or presence of any CNS disorder such as a seizure disorder, cerebrovascular&#xD;
               ischemia/hemorrhage with clinical signs or symptoms&#xD;
  &#xD;
            -  History of concomitant genetic syndrome such as Fanconi anemia, Kostmann syndrome,&#xD;
               Shwachman-Diamond or any known bone marrow failure syndrome&#xD;
  &#xD;
            -  History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or&#xD;
               other clinically significant cardiac disease within 12 months of enrollment&#xD;
  &#xD;
            -  Primary immunodeficiency&#xD;
  &#xD;
            -  Known infection with HIV, hepatitis B (HBsAg positive) or untreated hepatitis C virus&#xD;
  &#xD;
            -  Presence of fungal, bacterial, viral, or other infection that is uncontrolled or&#xD;
               requiring IV antimicrobials for management.&#xD;
  &#xD;
            -  Salvage chemotherapy including TKIs for Ph+ ALL within 1 week prior to enrollment&#xD;
  &#xD;
            -  Pregnant or breast feeding&#xD;
  &#xD;
            -  Patients with known autoimmune disease requiring the use of systemic immunosuppressive&#xD;
               therapy within the last year&#xD;
  &#xD;
            -  Corticosteroid therapy within 7 days prior to enrollment&#xD;
  &#xD;
            -  Acute or chronic GVHD requiring systemic treatment within 4 weeks prior to enrollment&#xD;
  &#xD;
            -  Live vaccine ≤ 4 weeks prior to enrollment&#xD;
  &#xD;
            -  Any medical condition that in the judgement of the investigator is likely to interfere&#xD;
               with assessment of safety or efficacy of study treatment&#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>Lori Muffly, M.D.</last_name>
      <role>Principal Investigator</role>
      <affiliation>Stanford University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Lindsay Danley</last_name>
      <phone>(650) 736-0304</phone>
      <email>lindsmd@stanford.edu</email>
    </overall_contact>
    <location>
      <facility>
        <name>Stanford University</name>
        <address>
          <city>Palo Alto</city>
          <state>California</state>
          <zip>94305</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Lindsay Danley</last_name>
        <phone>650-736-0304</phone>
        <email>lindsmd@stanford.edu</email>
      </contact>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>July 10, 2023</study_first_submitted>
    <study_first_submitted_qc>August 14, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 15, 2023</study_first_posted>
    <last_update_submitted>September 13, 2023</last_update_submitted>
    <last_update_submitted_qc>September 13, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 15, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Leukemia</keyword>
    <keyword>CAR T cell therapy</keyword>
    <keyword>Brexucabtagene Autoleucel</keyword>
    <keyword>Dasatinib</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>
      <mesh_term>Leukemia, Lymphoid</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Dasatinib</mesh_term>
    </intervention_browse>
    <!-- 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/NCT05993949
  org study id: IRB-68603
  nct id: NCT05993949
  lead sponsor: 
  collaborator: 
  is fda regulated drug: No
  is fda regulated device: No
  To assess the feasibility of oral dasatinib pulses (3 consecutive days per week) during the
        first month following infusion of brexucabtagene autoleucel (Tecartus) in adults with
        relapsed or refractory B-cell acute lymphoblastic leukemia.
  allocation: Non-Randomized
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Feasibility of dasatinib pulses
  time frame: 1 month
  description: Feasibility of administering oral dasatinib pulses (3 consecutive doses per week) during the first month following Tecartus infusion. Feasibility will be defined as the ability of 8 out of 20 subjects to miss no more than one cycle (defined as one week of at least three consecutive days of dasatinib) within the first month following Tecartus infusion.
  measure: Safety of oral dasatinib pulses
  time frame: 2 years
  description: Defined by a description of adverse events and serious adverse events at least possibly related to dasatinib following CAR T cell therapy; it will include an analysis of the sequential toxicity boundaries in that the analysis does not lead to a pause in the study; further defined as no reports of suspected death on study.
  measure: Overall response rate
  time frame: 3 months
  description: The definitions for response are primarily based on the standardized response criteria defined by National Comprehensive Cancer Network (NCCN) Guidelines (NCCN, 2021 v.2).
  measure: Complete Response (CR)
  time frame: 3 months
  description: The definitions for response are primarily based on the standardized response criteria defined by National Comprehensive Cancer Network (NCCN) Guidelines (NCCN, 2021 v.2).
  measure: MRD-negative Complete Response (CR)
  time frame: 3 months
  description: The definitions for response are primarily based on the standardized response criteria defined by National Comprehensive Cancer Network (NCCN) Guidelines (NCCN, 2021 v.2).
  measure: Duration of CR in responders
  time frame: 2 years
  measure: Progression Free Survival (PFS) following Tecartus plus dasatinib
  time frame: 2 years
  description: PFS is defined as the time from the start of the investigational therapy to the date of radiographic progression
  measure: Overall Survival (OS) following Tecartus plus dasatinib
  time frame: 2 years
  description: OS is defined as the time from the date of initial disease diagnosis to the date of death from any cause
  arm group label: Dasatinib
  arm group type: Experimental
  description: Oral dasatinib 100mg
  intervention type: Drug
  intervention name: Dasatinib
  description: 3 pulses of oral dasatinib (100 mg daily) beginning on Day 4 (+up to 2 days) for 3 days (with 4 days off), repeated weekly. The weekly 3-day pulse schedule of dasatinib may continue for up to 3 months in subjects who continue to meet the dasatinib eligibility criteria and who do not meet off treatment/off study criteria
  arm group label: Dasatinib
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Lori Muffly, M.D.
  role: Principal Investigator
  affiliation: Stanford University
  last name: Lindsay Danley
  phone: (650) 736-0304
  email: lindsmd@stanford.edu
  facility: 
  contact: 
  country: United States
  responsible party type: Sponsor
  mesh term: Leukemia
  mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
  mesh term: Leukemia, Lymphoid
  mesh term: Dasatinib