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/NCT05963217</url>
    </required_header>
    <id_info>
      <org_study_id>TBI-200101</org_study_id>
      <nct_id>NCT05963217</nct_id>
    </id_info>
    <brief_title>Study of TBI-2001(Autologous CD19 Specific Chimeric Antigen Receptor (CAR) Gene-transduced T Lymphocytes) for Relapsed or Refractory CD19+ B-cell Lymphoma, CLL/SLL</brief_title>
    <official_title>Phase I/Ib Study of TBI-2001 for Patients With Relapsed or Refractory CD19+ B-cell Lymphoma, Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University Health Network, Toronto</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Takara Bio Inc.</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>University Health Network, Toronto</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>
        This is a Phase 1/1b, open-label, dose-escalation study to evaluate the safety and the&#xD;
        efficacy of anti-CD19 chimeric antigen receptor (CAR) (TBI-2001) for relapsed or refractory&#xD;
        CD19+ B-cell lymphoma Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL).&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        TBI-2001 is a next-generation CAR-T product including costimulatory sequences that lead to&#xD;
        the activation of cytokine-related JAK/STAT signaling pathways. This is a first-in-human&#xD;
        study of TBI-2001 and will follow a 3+3 design of dose-escalation cohorts. Additional&#xD;
        subjects will be treated with TBI-2001 at the determined recommended phase 2 dose (RP2D)&#xD;
        following cyclophosphamide and fludarabine pre-treatment. Long-term follow-up is conducted&#xD;
        for 5 years following the infusion of TBI-2001&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">July 26, 2023</start_date>
    <completion_date type="Anticipated">November 30, 2025</completion_date>
    <primary_completion_date type="Anticipated">November 30, 2024</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>Safety of TBI-2001</measure>
      <time_frame>One month</time_frame>
      <description>Dose Limiting Toxicities (DLTs)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Safety of TBI-2001</measure>
      <time_frame>One year</time_frame>
      <description>Adverse event (AEs)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Safety of TBI-2001</measure>
      <time_frame>One year</time_frame>
      <description>Laboratory testing- RCR appearance and Clonality</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Recommended phase 2 dose (RP2D) of TBI-2001</measure>
      <time_frame>One year</time_frame>
      <description>RP2D to be determined during the dose escalation cohort</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Efficacy of TBI-2001; Overall Response Rate (ORR)</measure>
      <time_frame>One year</time_frame>
      <description>Overall Response Rate (ORR) (Complete Response (CR)+Partial Response(PR))</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Efficacy of TBI-2001; Durable Response Rate (DRR)</measure>
      <time_frame>One year</time_frame>
      <description>Durable Response Rate (DRR) as defined as CR or PR sustained for at least 6 months</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Efficacy of TBI-2001; Progression free survival (PFS)</measure>
      <time_frame>One year</time_frame>
      <description>Progression free survival</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Efficacy of TBI-2001; Overall survival (OS)</measure>
      <time_frame>One year</time_frame>
      <description>Overall survival</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Persistence of TBI-2001</measure>
      <time_frame>One year</time_frame>
      <description>Percentage of CAR T in peripheral blood and bone marrow using PCR and Flow cytometry.</description>
    </other_outcome>
    <other_outcome>
      <measure>Minimal residual disease (MRD) negative rate (in CLL patients)</measure>
      <time_frame>One year</time_frame>
      <description>MRD negative rate</description>
    </other_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">19</enrollment>
    <condition>Relapsed or Refractory CD19+ B-cell Lymphoma</condition>
    <condition>Relapsed or Refractory Chronic Lymphocytic Leukemia</condition>
    <condition>Relapsed or Refractory Small Lymphocytic Lymphoma</condition>
    <arm_group>
      <arm_group_label>Experimental: Dose Level 1 to 3</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>0.3 to 3 x 10^6 autologous CD19-CAR-T cells/kg per patient will be administered intravenously after a conditioning chemotherapy with cyclophosphamide and fludarabine.</description>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>TBI-2001</intervention_name>
      <description>Phase-I portion:&#xD;
  cohort 1: 3×10^5 cells/kg, cohort 2: 1×10^6 cells/kg, cohort 3: 3×10^6 cells/kg). Phase-Ib portion: The dose of Phase-Ib will be determined during the phase I portion.</description>
      <arm_group_label>Experimental: Dose Level 1 to 3</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Cyclophosphamide</intervention_name>
      <description>IV Cyclophosphamide (for 3 days) will be administered as conditioning before cell infusion with TBI-2001.</description>
      <arm_group_label>Experimental: Dose Level 1 to 3</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Fludarabine</intervention_name>
      <description>IV Fludarabine (for 3 days) will be administered as conditioning before cell infusion with TBI-2001.</description>
      <arm_group_label>Experimental: Dose Level 1 to 3</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Patients with histologically or cytologically confirmed CD19 positive B cell&#xD;
               Non-Hodgkin Lymphoma (NHL), Chronic Lymphocytic Leukemia (CLL), or Small Lymphocytic&#xD;
               Lymphoma (SLL) who have received at least 2 prior therapies.&#xD;
  &#xD;
            2. Phase Ib cohort will enroll CLL/SLL patients only.&#xD;
  &#xD;
            3. ECOG Performance Status 0 or 1.&#xD;
  &#xD;
            4. Age ≥18 years at time of consent.&#xD;
  &#xD;
            5. Life expectancy greater than 4 months.&#xD;
  &#xD;
            6. No anti-cancer chemotherapy, radiation therapy or immunotherapy within 2 weeks prior&#xD;
               to apheresis for generation of TBI-2001.&#xD;
  &#xD;
            7. Patients must have adequate key organ function (bone marrow, heart, lung, liver,&#xD;
               renal, etc)&#xD;
  &#xD;
            8. Consent must be appropriately obtained in accordance with applicable local and&#xD;
               regulatory requirements.&#xD;
  &#xD;
            9. The treating investigator should consider the patient to have disease that is&#xD;
               incurable, and that the patient would be a reasonable candidate for future treatment&#xD;
               with TBI-2001 within the next 3 months&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Uncontrolled intercurrent illnesses or medical conditions that may interfere with&#xD;
               trial participation.&#xD;
  &#xD;
            2. Active or prior documented autoimmune disease within the past 2 years.&#xD;
  &#xD;
            3. History of primary immunodeficiency.&#xD;
  &#xD;
            4. History of organ transplant that requires use of immunosuppressive medications.&#xD;
  &#xD;
            5. History hypersensitivity to components of manufacture or excipients of investigational&#xD;
               drug.&#xD;
  &#xD;
            6. Untreated central nervous system (CNS) metastases requiring concurrent treatment,&#xD;
               inclusive of but not limited to surgery, radiation, and/or corticosteroids.&#xD;
  &#xD;
            7. Other invasive malignancy within 2 years except for noninvasive malignancies&#xD;
  &#xD;
            8. Current or prior use of immunosuppressive medication within 14 days before apheresis.&#xD;
  &#xD;
            9. Any condition that, in the opinion of the investigator, would interfere with the&#xD;
               evaluation of TBI-2001 or interpretation of subject safety or study results.&#xD;
  &#xD;
           10. Known history of untreated active tuberculosis.&#xD;
  &#xD;
           11. HIV positivity.&#xD;
  &#xD;
           12. Active HTLV or syphilis infection.&#xD;
  &#xD;
           13. Active hepatitis B or active hepatitis C. Subjects with a negative PCR assay for viral&#xD;
               load for hepatitis B or C are permitted.&#xD;
  &#xD;
           14. Pregnant or lactating women.&#xD;
  &#xD;
           15. Received allogeneic-HSCT.&#xD;
  &#xD;
           16. Any prior CD19 directed therapy.&#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>Marcus Butler, M.D.</last_name>
      <role>Principal Investigator</role>
      <affiliation>Princess Margaret Cancer Centre</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Marcus Butler, M.D.</last_name>
      <phone>416-946-4501</phone>
      <phone_ext>2911</phone_ext>
      <email>tip@uhn.ca</email>
    </overall_contact>
    <location>
      <facility>
        <name>Princess Margaret Cancer Centre</name>
        <address>
          <city>Toronto</city>
          <state>Ontario</state>
          <zip>M5G 2M9</zip>
          <country>Canada</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Marcus Butler, M.D.</last_name>
        <phone>416-946-4501</phone>
        <phone_ext>5485</phone_ext>
        <email>marcus.butler@uhn.ca</email>
      </contact>
      <investigator>
        <last_name>Marcus Butler, M.D.</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>Canada</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>June 27, 2023</study_first_submitted>
    <study_first_submitted_qc>July 26, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">July 27, 2023</study_first_posted>
    <last_update_submitted>July 26, 2023</last_update_submitted>
    <last_update_submitted_qc>July 26, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">July 27, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>CD19+ B-cell Lymphoma</keyword>
    <keyword>Chronic Lymphocytic Leukemia</keyword>
    <keyword>CLL</keyword>
    <keyword>Small Lymphocytic Lymphoma</keyword>
    <keyword>SLL</keyword>
    <keyword>Lymphoma</keyword>
    <keyword>TBI-2001</keyword>
    <keyword>Anti-CD19 CAR Expressing T cell Therapy</keyword>
    <keyword>CD19 CAR Gene-Transduced Lymphocyte</keyword>
    <keyword>Adoptive Immunotherapy</keyword>
    <keyword>Genetically Engineered Lymphocyte Therapy</keyword>
    <keyword>Retroviral Vector</keyword>
    <keyword>Neoplasms by Histologic Type</keyword>
    <keyword>Neoplasms</keyword>
    <keyword>Neoplasms, Experimental</keyword>
    <keyword>Immune System Diseases</keyword>
    <keyword>Chimeric Antigen Receptor</keyword>
    <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>Leukemia, Lymphoid</mesh_term>
      <mesh_term>Lymphoma, B-Cell</mesh_term>
      <mesh_term>Leukemia, Lymphocytic, Chronic, B-Cell</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Cyclophosphamide</mesh_term>
      <mesh_term>Fludarabine</mesh_term>
    </intervention_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/NCT05963217
  org study id: TBI-200101
  nct id: NCT05963217
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  This is a Phase 1/1b, open-label, dose-escalation study to evaluate the safety and the
        efficacy of anti-CD19 chimeric antigen receptor (CAR) (TBI-2001) for relapsed or refractory
        CD19+ B-cell lymphoma Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL).
  TBI-2001 is a next-generation CAR-T product including costimulatory sequences that lead to
        the activation of cytokine-related JAK/STAT signaling pathways. This is a first-in-human
        study of TBI-2001 and will follow a 3+3 design of dose-escalation cohorts. Additional
        subjects will be treated with TBI-2001 at the determined recommended phase 2 dose (RP2D)
        following cyclophosphamide and fludarabine pre-treatment. Long-term follow-up is conducted
        for 5 years following the infusion of TBI-2001
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Safety of TBI-2001
  time frame: One month
  description: Dose Limiting Toxicities (DLTs)
  measure: Safety of TBI-2001
  time frame: One year
  description: Adverse event (AEs)
  measure: Safety of TBI-2001
  time frame: One year
  description: Laboratory testing- RCR appearance and Clonality
  measure: Recommended phase 2 dose (RP2D) of TBI-2001
  time frame: One year
  description: RP2D to be determined during the dose escalation cohort
  measure: Efficacy of TBI-2001; Overall Response Rate (ORR)
  time frame: One year
  description: Overall Response Rate (ORR) (Complete Response (CR)+Partial Response(PR))
  measure: Efficacy of TBI-2001; Durable Response Rate (DRR)
  time frame: One year
  description: Durable Response Rate (DRR) as defined as CR or PR sustained for at least 6 months
  measure: Efficacy of TBI-2001; Progression free survival (PFS)
  time frame: One year
  description: Progression free survival
  measure: Efficacy of TBI-2001; Overall survival (OS)
  time frame: One year
  description: Overall survival
  measure: Persistence of TBI-2001
  time frame: One year
  description: Percentage of CAR T in peripheral blood and bone marrow using PCR and Flow cytometry.
  measure: Minimal residual disease (MRD) negative rate (in CLL patients)
  time frame: One year
  description: MRD negative rate
  arm group label: Experimental: Dose Level 1 to 3
  arm group type: Experimental
  description: 0.3 to 3 x 10^6 autologous CD19-CAR-T cells/kg per patient will be administered intravenously after a conditioning chemotherapy with cyclophosphamide and fludarabine.
  intervention type: Biological
  intervention name: TBI-2001
  description: Phase-I portion:
  cohort 1: 3×10^5 cells/kg, cohort 2: 1×10^6 cells/kg, cohort 3: 3×10^6 cells/kg). Phase-Ib portion: The dose of Phase-Ib will be determined during the phase I portion.
  arm group label: Experimental: Dose Level 1 to 3
  intervention type: Drug
  intervention name: Cyclophosphamide
  description: IV Cyclophosphamide (for 3 days) will be administered as conditioning before cell infusion with TBI-2001.
  arm group label: Experimental: Dose Level 1 to 3
  intervention type: Drug
  intervention name: Fludarabine
  description: IV Fludarabine (for 3 days) will be administered as conditioning before cell infusion with TBI-2001.
  arm group label: Experimental: Dose Level 1 to 3
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Marcus Butler, M.D.
  role: Principal Investigator
  affiliation: Princess Margaret Cancer Centre
  last name: Marcus Butler, M.D.
  phone: 416-946-4501
  phone ext: 2911
  email: tip@uhn.ca
  facility: 
  status: Recruiting
  contact: 
  investigator: 
  country: Canada
  responsible party type: Sponsor
  mesh term: Lymphoma
  mesh term: Leukemia
  mesh term: Leukemia, Lymphoid
  mesh term: Lymphoma, B-Cell
  mesh term: Leukemia, Lymphocytic, Chronic, B-Cell
  mesh term: Cyclophosphamide
  mesh term: Fludarabine
  sharing ipd: No