<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/NCT03765177</url>
  </required_header>
  <id_info>
    <org_study_id>CLIC-01 Study</org_study_id>
    <nct_id>NCT03765177</nct_id>
  </id_info>
  <brief_title>CLIC-1901 for the Treatment of Patients With Relapsed/Refractory CD19 Positive Hematologic Malignancies</brief_title>
  <acronym>CLIC-01</acronym>
  <official_title>Canadian-Led Immunotherapies in Cancer: CLIC-1901 for the Treatment of Patients With Relapsed/Refractory CD19 Positive Hematologic Malignancies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ottawa Hospital Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ottawa Hospital Research Institute</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>
      The investigators propose an early phase study defined as a phase I/II trial assessing&#xD;
      safety, feasibility and efficacy of CLIC-1901 autologous anti-CD19 Chimeric Antigen Receptor&#xD;
      T cells (CAR-T) cells for participants with relapsed/refractory CD19 positive (CD19+) Acute&#xD;
      Lymphoblastic Leukemia (ALL) and non-Hodgkin's Lymphoma (NHL). The Initial Stage of the study&#xD;
      (n=20 participants) will focus on feasibility and safety while the Extended Stage will&#xD;
      include all participants enrolled in the study (n=additional 40 participants for a total of&#xD;
      60) and will focus on efficacy and safety outcomes. In the proposed trial, we will administer&#xD;
      our CAR-T cell product to these participants as a single infusion. Participants will undergo&#xD;
      (a) lymphodepletion with cyclophosphamide and fludarabine, followed by (b) infusion of&#xD;
      autologous CLIC-1901 CAR-T cells. All treatments will be delivered intravenously.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigators have designed a two-stage, single-arm, open-label early phase study to&#xD;
      determine the safety and efficacy of CLIC-1901 cell therapy in patients with CD19+ ALL and&#xD;
      NHL. The primary objective in the initial stage of 20 participants will be to evaluate the&#xD;
      feasibility of our protocol and the safety and tolerability of infusing autologous CLIC-1901&#xD;
      cells into patients with relapsed/refractory CD19+ ALL or NHL. Once 20 participants have been&#xD;
      treated and the treatment is deemed safe, up to 40 more participants will be enrolled in an&#xD;
      extension stage where the primary objective will be overall response rate (defined as&#xD;
      complete or partial response) at 6 months after CLIC-1901 infusion.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 16, 2019</start_date>
  <completion_date type="Anticipated">October 31, 2022</completion_date>
  <primary_completion_date type="Anticipated">October 2022</primary_completion_date>
  <phase>Phase 1/Phase 2</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>Proportion of participants experiencing either Grade 3 or 4 cytokine release syndrome.</measure>
    <time_frame>Within the first 28 days of CAR-T infusion</time_frame>
    <description>Grade 3 or 4 neurological toxicity, other Grade 3 or 4 toxicity (by CTCAE 4.03) or non-relapse related death.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Proportion of participants with complete (CR) or partial response (PR) to CLIC-1901</measure>
    <time_frame>6 months after CAR-T cell infusion</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Meeting enrollment targets</measure>
    <time_frame>First 20 participants within 12 months and next 40 participants within 2 years of opening the second stage.</time_frame>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Acute Lymphoblastic Leukemia</condition>
  <condition>Non-Hodgkin's Lymphoma</condition>
  <condition>Chronic Lymphocytic Leukemia</condition>
  <arm_group>
    <arm_group_label>CLIC-1901</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A single Intravenous infusion of CLIC-1901 will be given.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>CLIC-1901</intervention_name>
    <description>Participants will undergo (a) lymphodepletion with cyclophosphamide and fludarabine, followed by (b) infusion of autologous CLIC-1901 CAR-T cells. All treatments will be delivered intravenously.</description>
    <arm_group_label>CLIC-1901</arm_group_label>
    <other_name>autologous anti-CD19 CAR-T cells</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Participant must have relapsed or refractory CD19+ disease as defined by one of the&#xD;
             following:&#xD;
&#xD;
             a. Relapsed or refractory acute lymphoblastic leukemia or chronic lymphocytic leukemia&#xD;
             as defined by one of the following: i. Second or greater relapse ii. Any relapse after&#xD;
             allogeneic stem cell transplantation (SCT) iii. Chemorefractory as defined by not&#xD;
             achieving CR after 2 cycles of a standard induction chemotherapy or one cycle of&#xD;
             salvage therapy b. Histologically confirmed B-cell non-Hodgkin's lymphoma including&#xD;
             but not limited to diffuse large B-cell lymphoma (DLBCL) not otherwise specified,&#xD;
             primary mediastinal large B-cell lymphoma, or transformed follicular lymphoma,&#xD;
             Richter's, Burkitt's or Mantle Cell lymphoma with one of the following: i. Second or&#xD;
             greater relapse ii. Any relapse after autologous or allogeneic SCT iii.&#xD;
             Chemorefractory as defined by not achieving CR after 2 cycles of a standard&#xD;
             chemotherapy or one cycle of salvage therapy&#xD;
&#xD;
          2. All eligible participants must have documentation of CD19 tumour expression&#xD;
             demonstrated in tissue biopsy, bone marrow or peripheral blood within the 3 months&#xD;
             prior to study screening.&#xD;
&#xD;
          3. Adequate organ function&#xD;
&#xD;
          4. Participant age: 18 to 75 years.&#xD;
&#xD;
          5. Provide written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        An individual who meets any of the following criteria will be excluded from participation&#xD;
        in this study:&#xD;
&#xD;
          1. Isolated extra-medullary disease.&#xD;
&#xD;
          2. Participants with concomitant genetic syndrome, such as Fanconi anemia, Kostmann&#xD;
             syndrome, Shwachman syndrome or any other known familial bone marrow failure syndrome.&#xD;
&#xD;
          3. Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative&#xD;
             intent and with no evidence of active disease.&#xD;
&#xD;
          4. Prior treatment with any gene therapy product.&#xD;
&#xD;
          5. Participants with polymerase chain reaction (PCR) positive hepatitis B, hepatitis C,&#xD;
             or Human Immunodeficiency Virus (tested within 8 weeks of screening), or any&#xD;
             uncontrolled infection at screening.&#xD;
&#xD;
          6. Presence of active Graft Versus Host Disease requiring systemic therapy.&#xD;
&#xD;
          7. Participants who have undergone allogeneic SCT less than 6 months prior to CLIC-1901&#xD;
             cell infusion or who have undergone donor lymphocyte infusion less than 6 weeks prior&#xD;
             to CLIC-1901 cell infusion.&#xD;
&#xD;
          8. Active Central Nervous System (CNS) involvement by malignancy, defined by CNS-3 per&#xD;
             National Comprehensive Cancer Network guidelines.&#xD;
&#xD;
          9. History of anaphylaxis to gentamicin or its derivatives.&#xD;
&#xD;
         10. Participant has received an investigational agent within the 30 days prior to&#xD;
             enrolment visit.&#xD;
&#xD;
         11. Pregnant or nursing women.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Natasha Kekre, MD</last_name>
    <phone>613-737-8899</phone>
    <phone_ext>71064</phone_ext>
    <email>nkekre@toh.on.ca</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Alice Black</last_name>
    <phone>613-737-8899</phone>
    <phone_ext>71064</phone_ext>
    <email>aliblack@ohri.ca</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Vancouver General Hospital</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <zip>V5Z1M9</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kevin Hay, MD</last_name>
      <phone>604-675-8266</phone>
      <email>Kevin.Hay@bccancer.bc.ca</email>
    </contact>
    <contact_backup>
      <last_name>Justine Dimou, BSc</last_name>
      <phone>604-875-4111</phone>
      <phone_ext>61971</phone_ext>
      <email>justine.dimou@bccancer.bc.ca</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>The Ottawa Hospital - General Campus</name>
      <address>
        <city>Ottawa</city>
        <state>Ontario</state>
        <zip>K1H 8L6</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Natasha Kekre, MD, MPH, FRCP</last_name>
      <phone>613-737-8899</phone>
      <phone_ext>71064</phone_ext>
      <email>nkekre@toh.on.ca</email>
    </contact>
    <contact_backup>
      <last_name>Alice Black</last_name>
      <phone>613-737-8899</phone>
      <phone_ext>71064</phone_ext>
      <email>aliblack@ohri.ca</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>December 4, 2018</study_first_submitted>
  <study_first_submitted_qc>December 4, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 5, 2018</study_first_posted>
  <last_update_submitted>March 26, 2022</last_update_submitted>
  <last_update_submitted_qc>March 26, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 6, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Chimeric Antigen Receptor T cells</keyword>
  <keyword>CLIC-1901</keyword>
  <keyword>anti-CD19 CAR-T cells</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, Lymphocytic, Chronic, B-Cell</mesh_term>
    <mesh_term>Hematologic Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03765177
org study id: CLIC-01 Study
nct id: NCT03765177
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The investigators propose an early phase study defined as a phase I/II trial assessing
      safety, feasibility and efficacy of CLIC-1901 autologous anti-CD19 Chimeric Antigen Receptor
      T cells (CAR-T) cells for participants with relapsed/refractory CD19 positive (CD19+) Acute
      Lymphoblastic Leukemia (ALL) and non-Hodgkin's Lymphoma (NHL). The Initial Stage of the study
      (n=20 participants) will focus on feasibility and safety while the Extended Stage will
      include all participants enrolled in the study (n=additional 40 participants for a total of
      60) and will focus on efficacy and safety outcomes. In the proposed trial, we will administer
      our CAR-T cell product to these participants as a single infusion. Participants will undergo
      (a) lymphodepletion with cyclophosphamide and fludarabine, followed by (b) infusion of
      autologous CLIC-1901 CAR-T cells. All treatments will be delivered intravenously.
The investigators have designed a two-stage, single-arm, open-label early phase study to
      determine the safety and efficacy of CLIC-1901 cell therapy in patients with CD19+ ALL and
      NHL. The primary objective in the initial stage of 20 participants will be to evaluate the
      feasibility of our protocol and the safety and tolerability of infusing autologous CLIC-1901
      cells into patients with relapsed/refractory CD19+ ALL or NHL. Once 20 participants have been
      treated and the treatment is deemed safe, up to 40 more participants will be enrolled in an
      extension stage where the primary objective will be overall response rate (defined as
      complete or partial response) at 6 months after CLIC-1901 infusion.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Proportion of participants experiencing either Grade 3 or 4 cytokine release syndrome.
time frame: Within the first 28 days of CAR-T infusion
description: Grade 3 or 4 neurological toxicity, other Grade 3 or 4 toxicity (by CTCAE 4.03) or non-relapse related death.
measure: Proportion of participants with complete (CR) or partial response (PR) to CLIC-1901
time frame: 6 months after CAR-T cell infusion
measure: Meeting enrollment targets
time frame: First 20 participants within 12 months and next 40 participants within 2 years of opening the second stage.
arm group label: CLIC-1901
arm group type: Experimental
description: A single Intravenous infusion of CLIC-1901 will be given.
intervention type: Biological
intervention name: CLIC-1901
description: Participants will undergo (a) lymphodepletion with cyclophosphamide and fludarabine, followed by (b) infusion of autologous CLIC-1901 CAR-T cells. All treatments will be delivered intravenously.
arm group label: CLIC-1901
other name: autologous anti-CD19 CAR-T cells
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Natasha Kekre, MD
phone: 613-737-8899
phone ext: 71064
email: nkekre@toh.on.ca
last name: Alice Black
phone: 613-737-8899
phone ext: 71064
email: aliblack@ohri.ca
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
contact backup: 
country: Canada
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Leukemia, Lymphocytic, Chronic, B-Cell
mesh term: Hematologic Neoplasms
sharing ipd: Undecided