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/NCT06027957</url>
    </required_header>
    <id_info>
      <org_study_id>ISC19.26</org_study_id>
      <nct_id>NCT06027957</nct_id>
    </id_info>
    <brief_title>CD19 CAR T-Cell Therapy for R/R Non-Hodgkin Lymphoma and Acute Lymphoblastic Leukemia</brief_title>
    <official_title>Phase I Clinical Trial Evaluating the Safety and Efficacy of Point-of-care CAR-T-cell Therapy in the Treatment of Relapsed/Refractory CD19+ Non-Hodgkin Lymphoma and Acute Lymphoblastic Leukemia</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Vinmec Research Institute of Stem Cell and Gene Technology</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>National Institute of Hematology and Blood Transfusion, Vietnam</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Vinmec Research Institute of Stem Cell and Gene Technology</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        -  Brief Summary: Cluster of differentiation 19 (CD19) is expressed on B cells. CD19+ tumor&#xD;
             cells in patients with non-Hodgkin lymphoma and acute lymphoblastic leukemia can be&#xD;
             targeted using T cells expressing CD19-specific chimeric antigen receptor (CAR).&#xD;
  &#xD;
          -  Objective: This study aims to evaluate the safety and efficacy of single-dose anti-CD19&#xD;
             CAR T-cell therapy in the treatment of relapsed/refractory CD19+ non-Hodgkin lymphoma&#xD;
             and acute lymphoblastic leukemia.&#xD;
  &#xD;
          -  Eligibility: People aged 1 to 60 years with relapsed/refractory CD19+ non-Hodgkin&#xD;
             lymphoma and acute lymphoblastic leukemia.&#xD;
  &#xD;
          -  Design: Phase 1 clinical trial, uncontrolled, single dose of CD19 CAR T-cells.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Objectives:&#xD;
  &#xD;
          -  Evaluate the frequency and severity of adverse events and serious adverse events&#xD;
             (AEs/SAEs) of the therapy.&#xD;
  &#xD;
          -  Evaluate the response rate after CD19 CAR T-cell infusion according to the following&#xD;
             criteria:&#xD;
  &#xD;
               -  Proportion of patients with complete response and partial response after CD19 CAR&#xD;
                  T-cell infusion&#xD;
  &#xD;
               -  Progression-free survival (PFS) after infusion of CD19 CAR T-cells&#xD;
  &#xD;
               -  Event-free survival (EFS) after infusion of CD19 CAR T-cells&#xD;
  &#xD;
               -  Overall survival (OS) after infusion of CD19 CAR T-cells&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">August 2, 2023</start_date>
    <completion_date type="Anticipated">July 31, 2025</completion_date>
    <primary_completion_date type="Anticipated">July 31, 2025</primary_completion_date>
    <phase>Phase 1</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Assessment of the frequency and severity of adverse events and serious adverse events (AEs/SAEs) of the therapy</measure>
      <time_frame>6 months</time_frame>
      <description>The incidence of adverse events (AEs) and serious adverse events (SAEs) will be recorded and classified according to CTCAE v5 (grade 1-5). CRS and ICANs will be classified using the ASTCT criteria (grade 1-5). These parameters will be used to assess the safety of the therapy.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Proportion of patients with complete response and partial response after CD19 CAR T-cell infusion (%)</measure>
      <time_frame>Day 30 and day 90 after CAR-T infusion for B-ALL; day 90 after CAR-T infusion for NHL</time_frame>
      <description>Patients with B-ALL will receive bone marrow biopsy assessed on day 30 and day 90 to check blast frequency and MRD. The response will be classified according to NCCN guidelines.&#xD;
  Patients with NHL will be examined PET-CT or CT on day 90. The response will be classified according to Cheson guidelines.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progression-free survival (PFS) (months)</measure>
      <time_frame>6 months</time_frame>
      <description>PFS is defined as the time from CAR T-cell infusion, until disease progression or death from any cause. Progression is defined as an increase of tumor load, the development of new lesions.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Event-free survival (EFS) (months)</measure>
      <time_frame>6 months</time_frame>
      <description>EFS is defined as time to treatment failure (including complete remission with incomplete hematologic or platelet recovery), relapse from complete remission, or death from any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall survival (OS) (months)</measure>
      <time_frame>6 months</time_frame>
      <description>EFS is defined as time to death</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">16</enrollment>
    <condition>B-Cell Non Hodgkin Lymphoma</condition>
    <condition>B-Cell Acute Lymphoblastic Leukemia</condition>
    <arm_group>
      <arm_group_label>Treatment Regimen</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Experimental: Treatment Regimen.&#xD;
  Leukapheresis to collect white blood cells using Spectra Optia Apheresis system.&#xD;
  T cells selection, transduction, and CAR T-cell manufacturing using CliniMACS Prodigy. During this process, T cells will be genetically modified to express CD19 CAR.&#xD;
  Lymphodepleting chemotherapy conditioning regimen for 3 days.&#xD;
  CAR T-cells targeting CD19 will be infused intravenously at a dose between 1 and 2x10e6 cells/kg for 15-30 minutes.&#xD;
  Following the T-cell infusion, patients will stay in the clinic for approximately 21-28 days to monitor toxicity.&#xD;
  Outpatient follow-up will take place after 1 month, 3 months, and 6 months after infusion.</description>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>anti-CD19 CAR T-cells</intervention_name>
      <description>For Biological: CD19 CAR T-cells&#xD;
  Dose: 1-2.10e6 cells/kg of weight&#xD;
  Route: intravenous infusion&#xD;
  For Chemotherapy Drug:&#xD;
  Fludarabine (30 mg/m2/day) given intravenously (IV) on day -5 to -3.&#xD;
  Cyclophosphamide 500 mg/m2/day for NHL and 250 mg/m2/day for ALL given IV from day -5 to -3.&#xD;
  Mesna 500 mg/m2/day for NHL and 250 mg/m2/day for ALL, divided in three infusions: one day before the cyclophosphamide infusion, and 4 and 8 hours after.</description>
      <arm_group_label>Treatment Regimen</arm_group_label>
      <other_name>Chemotherapy Drug</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion criteria:&#xD;
  &#xD;
            -  B-cell acute lymphoblastic leukemia: refractory to two cycles of chemotherapy,&#xD;
               relapsed after chemotherapy, or hematopoietic stem cell transplantation.&#xD;
  &#xD;
            -  B-cell non-Hodgkin lymphoma: refractory to two lines of chemotherapy, relapsed after&#xD;
               chemotherapy, or hematopoietic stem cell transplantation.&#xD;
  &#xD;
            -  Age: From 1 to 60 years old (both males and females)&#xD;
  &#xD;
            -  Adequate organ functions:&#xD;
  &#xD;
                 -  Serum creatinine ≤ 1.5 x ULN or eGFR ≥ 60 mL/min/1.73 m2&#xD;
  &#xD;
                 -  ALT and AST ≤ 5 x ULN; Bilirubin ≤ 2.0 mg/dl&#xD;
  &#xD;
                 -  No chronic lung diseases, such as obstructive pulmonary disease or bronchial&#xD;
                    asthma, required continuous medications without respiratory failure (SpO2 oxygen&#xD;
                    saturation &gt; 92% at room temperature).&#xD;
  &#xD;
                 -  No arrhythmia, no intracardiac thrombus or vascular wall, no heart failure, LVEF&#xD;
                    ≥ 45%&#xD;
  &#xD;
            -  Blood test:&#xD;
  &#xD;
                 -  Absolute neutrophil count (ANC) ≥ 1,000/mm3 (1 G/l) without filgrastim&#xD;
  &#xD;
                 -  Absolute lymphocyte count ≥ 100/mm3 (0.1 G/l)&#xD;
  &#xD;
                 -  Absolute platelet count ≥ 75,000/mm3 (75 G/l)&#xD;
  &#xD;
                 -  Hemoglobin ≥ 8.0 g/dl&#xD;
  &#xD;
            -  Positive for CD19 measured by immunohistochemistry or flow cytometry.&#xD;
  &#xD;
            -  Agree to participate in the study&#xD;
  &#xD;
            -  Agree to use safe methods of contraception for female patients.&#xD;
  &#xD;
          Exclusion criteria:&#xD;
  &#xD;
            -  Involved central nervous system invasion at the time of screening.&#xD;
  &#xD;
            -  Medical history of veno-occlusive disease (VOD).&#xD;
  &#xD;
            -  Required acute treatment due to tumors such as intestinal obstructions, vascular&#xD;
               compression, or respiratory failure.&#xD;
  &#xD;
            -  Having active hemolytic anemia.&#xD;
  &#xD;
            -  Diagnosed with primary immunodeficiency.&#xD;
  &#xD;
            -  Medical history of autoimmune neurological diseases or neuromyelitis.&#xD;
  &#xD;
            -  Receiving immunosuppressive medication, except for ≤ 30 mg prednisolone or equivalent&#xD;
               at the time of CAR-T-cell transfusion.&#xD;
  &#xD;
            -  Having acute, progressive, or chronic graft-versus-host disease (GvHD).&#xD;
  &#xD;
            -  Having active infectious diseases determined by clinical, imaging, or other laboratory&#xD;
               tests (blood culture, PCR, etc.)&#xD;
  &#xD;
            -  Patients who are critically ill or at risk of premature death characterized by:&#xD;
  &#xD;
                 -  Acute liver failure requiring dialysis&#xD;
  &#xD;
                 -  Heart failure requiring vasopressors&#xD;
  &#xD;
                 -  Systemic infection unresponsive to antibiotics&#xD;
  &#xD;
                 -  ECOG performance status ≥ 3 points at the time of screening&#xD;
  &#xD;
            -  Having other severe concomitant diseases (e.g., uncontrolled arterial hypertension,&#xD;
               heart failure NYHA III-IV).&#xD;
  &#xD;
            -  Unstable angina within 3 months prior to screening.&#xD;
  &#xD;
            -  Any previous or concurrent malignancy was not B-cell lymphoma or B-ALL.&#xD;
  &#xD;
            -  Medical history of clinically relevant central nervous system disease, such as&#xD;
               epilepsy, convulsions, paralysis, aphasia, uncontrolled cerebrovascular disease,&#xD;
               traumatic brain injury, and Parkinson's disease.&#xD;
  &#xD;
            -  Intolerance to excipients from cellular products.&#xD;
  &#xD;
            -  Pregnant women or those who expect to be pregnant or reastfeeding.&#xD;
  &#xD;
            -  Other diseases or other conditions and circumstances that, according to the&#xD;
               investigator's assessment, make it difficult to ensure compliance with study&#xD;
               treatment.&#xD;
  &#xD;
            -  Participation in another clinical trial at the time of screening&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>1 Year</minimum_age>
      <maximum_age>60 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Thanh Liem Nguyen, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Vinmec Research Institute of Stem Cell and Gene Technology</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Thanh Liem Nguyen, PhD</last_name>
      <phone>+84 4 3974 3556</phone>
      <phone_ext>1420</phone_ext>
      <email>v.liemnt@vinmec.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Van T. Hoang, PhD</last_name>
      <phone>+84 93 644 94 81</phone>
      <email>v.vanht8@vinmec.com</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Vinmec Research Institute of Stem Cell and Gene Technology</name>
        <address>
          <city>Hanoi</city>
          <zip>100000</zip>
          <country>Vietnam</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Nguyen T Liem, Prof</last_name>
      </contact>
    </location>
    <location_countries>
      <country>Vietnam</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>July 28, 2023</study_first_submitted>
    <study_first_submitted_qc>September 5, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 7, 2023</study_first_posted>
    <last_update_submitted>September 5, 2023</last_update_submitted>
    <last_update_submitted_qc>September 5, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 7, 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>Leukemia</mesh_term>
      <mesh_term>Lymphoma, Non-Hodgkin</mesh_term>
      <mesh_term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</mesh_term>
      <mesh_term>Leukemia, Lymphoid</mesh_term>
      <mesh_term>Lymphoma, B-Cell</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </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/NCT06027957
  org study id: ISC19.26
  nct id: NCT06027957
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  -  Brief Summary: Cluster of differentiation 19 (CD19) is expressed on B cells. CD19+ tumor
             cells in patients with non-Hodgkin lymphoma and acute lymphoblastic leukemia can be
             targeted using T cells expressing CD19-specific chimeric antigen receptor (CAR).
  
          -  Objective: This study aims to evaluate the safety and efficacy of single-dose anti-CD19
             CAR T-cell therapy in the treatment of relapsed/refractory CD19+ non-Hodgkin lymphoma
             and acute lymphoblastic leukemia.
  
          -  Eligibility: People aged 1 to 60 years with relapsed/refractory CD19+ non-Hodgkin
             lymphoma and acute lymphoblastic leukemia.
  
          -  Design: Phase 1 clinical trial, uncontrolled, single dose of CD19 CAR T-cells.
  Objectives:
  
          -  Evaluate the frequency and severity of adverse events and serious adverse events
             (AEs/SAEs) of the therapy.
  
          -  Evaluate the response rate after CD19 CAR T-cell infusion according to the following
             criteria:
  
               -  Proportion of patients with complete response and partial response after CD19 CAR
                  T-cell infusion
  
               -  Progression-free survival (PFS) after infusion of CD19 CAR T-cells
  
               -  Event-free survival (EFS) after infusion of CD19 CAR T-cells
  
               -  Overall survival (OS) after infusion of CD19 CAR T-cells
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Assessment of the frequency and severity of adverse events and serious adverse events (AEs/SAEs) of the therapy
  time frame: 6 months
  description: The incidence of adverse events (AEs) and serious adverse events (SAEs) will be recorded and classified according to CTCAE v5 (grade 1-5). CRS and ICANs will be classified using the ASTCT criteria (grade 1-5). These parameters will be used to assess the safety of the therapy.
  measure: Proportion of patients with complete response and partial response after CD19 CAR T-cell infusion (%)
  time frame: Day 30 and day 90 after CAR-T infusion for B-ALL; day 90 after CAR-T infusion for NHL
  description: Patients with B-ALL will receive bone marrow biopsy assessed on day 30 and day 90 to check blast frequency and MRD. The response will be classified according to NCCN guidelines.
  Patients with NHL will be examined PET-CT or CT on day 90. The response will be classified according to Cheson guidelines.
  measure: Progression-free survival (PFS) (months)
  time frame: 6 months
  description: PFS is defined as the time from CAR T-cell infusion, until disease progression or death from any cause. Progression is defined as an increase of tumor load, the development of new lesions.
  measure: Event-free survival (EFS) (months)
  time frame: 6 months
  description: EFS is defined as time to treatment failure (including complete remission with incomplete hematologic or platelet recovery), relapse from complete remission, or death from any cause.
  measure: Overall survival (OS) (months)
  time frame: 6 months
  description: EFS is defined as time to death
  arm group label: Treatment Regimen
  arm group type: Experimental
  description: Experimental: Treatment Regimen.
  Leukapheresis to collect white blood cells using Spectra Optia Apheresis system.
  T cells selection, transduction, and CAR T-cell manufacturing using CliniMACS Prodigy. During this process, T cells will be genetically modified to express CD19 CAR.
  Lymphodepleting chemotherapy conditioning regimen for 3 days.
  CAR T-cells targeting CD19 will be infused intravenously at a dose between 1 and 2x10e6 cells/kg for 15-30 minutes.
  Following the T-cell infusion, patients will stay in the clinic for approximately 21-28 days to monitor toxicity.
  Outpatient follow-up will take place after 1 month, 3 months, and 6 months after infusion.
  intervention type: Biological
  intervention name: anti-CD19 CAR T-cells
  description: For Biological: CD19 CAR T-cells
  Dose: 1-2.10e6 cells/kg of weight
  Route: intravenous infusion
  For Chemotherapy Drug:
  Fludarabine (30 mg/m2/day) given intravenously (IV) on day -5 to -3.
  Cyclophosphamide 500 mg/m2/day for NHL and 250 mg/m2/day for ALL given IV from day -5 to -3.
  Mesna 500 mg/m2/day for NHL and 250 mg/m2/day for ALL, divided in three infusions: one day before the cyclophosphamide infusion, and 4 and 8 hours after.
  arm group label: Treatment Regimen
  other name: Chemotherapy Drug
  criteria: 
  gender: All
  minimum age: 1 Year
  maximum age: 60 Years
  healthy volunteers: No
  last name: Thanh Liem Nguyen, PhD
  role: Principal Investigator
  affiliation: Vinmec Research Institute of Stem Cell and Gene Technology
  last name: Thanh Liem Nguyen, PhD
  phone: +84 4 3974 3556
  phone ext: 1420
  email: v.liemnt@vinmec.com
  last name: Van T. Hoang, PhD
  phone: +84 93 644 94 81
  email: v.vanht8@vinmec.com
  facility: 
  status: Recruiting
  contact: 
  country: Vietnam
  responsible party type: Sponsor
  mesh term: Lymphoma
  mesh term: Leukemia
  mesh term: Lymphoma, Non-Hodgkin
  mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
  mesh term: Leukemia, Lymphoid
  mesh term: Lymphoma, B-Cell
  sharing ipd: No