<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/NCT03795779</url>
  </required_header>
  <id_info>
    <org_study_id>ICG141-001</org_study_id>
    <nct_id>NCT03795779</nct_id>
  </id_info>
  <brief_title>CLL1-CD33 cCAR in Patients With Relapsed and/or Refractory, High Risk Hematologic Malignancies</brief_title>
  <official_title>Phase I, Interventional, Single Arm, Open Label, Treatment Study to Evaluate The Safety and Tolerability of CLL1-CD33 cCAR in Patients With Relapsed and/or Refractory, High Risk Hematologic Malignancies.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>iCell Gene Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The General Hospital of Western Theater Command</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>iCAR Bio Therapeutics Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Peking University Shenzhen Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>iCell Gene Therapeutics</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>
      Phase I, interventional, single arm, open label, treatment study to evaluate the safety and&#xD;
      tolerability of CLL1-CD33 cCAR in patients with relapsed and/or refractory, high risk&#xD;
      hematologic malignancies.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      AML bears heterogeneous cells that can consequently offset killing by single-CAR-based&#xD;
      therapy, which results in disease relapse. Leukemic stem cells (LSCs) associated with CLL1&#xD;
      expression comprise a rare population that also plays an important role in disease&#xD;
      progression and relapse for myeloid malignancies. CD33 is widely expressed in AML, high risk&#xD;
      myelodysplastic syndromes (MDS) and myeloproliferative neoplasms. Targeting both CD33 and&#xD;
      CLL1 surface antigens together may offer two distinct benefits. First, targeting both bulk&#xD;
      disease and leukemic stem cells together allows for a more comprehensive ablation of the&#xD;
      disease. Second, dual targeting of myeloid malignancies by both CD33 and CLL1 directed&#xD;
      therapy overcomes the pitfalls of single-antigen therapy by preventing relapse due to antigen&#xD;
      loss. While loss of a single antigen under antigen-specific selection pressure is possible,&#xD;
      loss of two antigens simultaneously is much less likely.&#xD;
&#xD;
      CLL1-CD33 cCAR is a compound Chimeric Antigen Receptor (cCAR) immunotherapy with two distinct&#xD;
      functional CAR molecules expressed on a T-cell, directed against the surface proteins CLL1&#xD;
      and CD33. cCAR intends to target the mechanisms of single-CAR relapse, specifically antigen&#xD;
      escape and leukemic stem cells.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">March 1, 2018</start_date>
  <completion_date type="Anticipated">September 30, 2022</completion_date>
  <primary_completion_date type="Anticipated">September 30, 2022</primary_completion_date>
  <phase>Early 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>Number of participants with dose limiting toxicity (DLT) as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0</measure>
    <time_frame>28 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Type of dose-limiting toxicity (DLT)</measure>
    <time_frame>28 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with adverse event by severity as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0</measure>
    <time_frame>2 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Response Rate (ORR)</measure>
    <time_frame>1 year</time_frame>
    <description>Assessment of morphologic complete remission (CR), complete remission with incomplete recovery of counts (CR1), no residual disease as analyzed by flow cytometry analysis, and molecular remission by molecular studies</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Hematologic Malignancy</condition>
  <condition>Acute Myeloid Leukemia</condition>
  <condition>Myelodysplastic Syndromes</condition>
  <condition>Myeloproliferative Neoplasm</condition>
  <condition>Chronic Myeloid Leukemia</condition>
  <arm_group>
    <arm_group_label>CLL1-CD33 cCAR T cells</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>CLL1-CD33cCAR T cells transduced with a lentiviral vector to express two distinct units of anti-CLL1 and CD33 CARs</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>CLL1-CD33 cCAR T cells</intervention_name>
    <description>CLL1-CD33 cCAR T cells transduced with a lentiviral vector to express two distinct units of anti-CLL1 and CD33 CARs.</description>
    <arm_group_label>CLL1-CD33 cCAR T cells</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Prior HSCT relapse beyond 6 months without active GVHD; systematic usage of&#xD;
             immunosuppressive drug or corticosteroid must have been stopped for more than 4 weeks&#xD;
&#xD;
          2. De novo AML&#xD;
&#xD;
          3. Transformed AML&#xD;
&#xD;
          4. MDS with excess blasts (RAEB-2)&#xD;
&#xD;
          5. MDS that is not a candidate for induction chemotherapy.&#xD;
&#xD;
          6. Myeloproliferative neoplasms with blastic transformation&#xD;
&#xD;
          7. Patients have exhausted standard therapeutic options&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Prior solid organ transplantation&#xD;
&#xD;
          2. Potentially curative therapy including hematopoietic cell transplant&#xD;
&#xD;
          3. Prior treatment with CD123xCD3 or CLL1x3 bispecific agents, T cells expressing CD123&#xD;
             CAR or CLL1 CAR, or toxin-conjugated to CD123 or CLL1 antibodies.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hongyu Zhang, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Peking University Shenzhen Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Fang Liu, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The General Hospital of Western Theater Command</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Kevin Pinz</last_name>
    <phone>6315386218</phone>
    <email>kevin.pinz@icellgene.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>The General Hospital of Western Theater Command</name>
      <address>
        <city>Chengdu</city>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Fang Liu, MD, PhD</last_name>
    </contact>
    <contact_backup>
      <email>lfyh2006@yahoo.com</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Peking University Shenzhen Hospital</name>
      <address>
        <city>Shenzhen</city>
        <country>China</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Hongyu Zhang, MD, PhD</last_name>
    </contact>
    <contact_backup>
      <email>HongyuZhang@pkuszh.com</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>January 2, 2019</study_first_submitted>
  <study_first_submitted_qc>January 4, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 8, 2019</study_first_posted>
  <last_update_submitted>May 17, 2021</last_update_submitted>
  <last_update_submitted_qc>May 17, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 19, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>CLL1</keyword>
  <keyword>CD33</keyword>
  <keyword>CLL1-CD33 cCAR</keyword>
  <keyword>Leukemia</keyword>
  <keyword>Hematologic Malignancies</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Leukemia, Myeloid</mesh_term>
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Hematologic Neoplasms</mesh_term>
    <mesh_term>Leukemia, Myelogenous, Chronic, BCR-ABL Positive</mesh_term>
    <mesh_term>Myelodysplastic Syndromes</mesh_term>
    <mesh_term>Myeloproliferative Disorders</mesh_term>
  </condition_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/NCT03795779
org study id: ICG141-001
nct id: NCT03795779
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Phase I, interventional, single arm, open label, treatment study to evaluate the safety and
      tolerability of CLL1-CD33 cCAR in patients with relapsed and/or refractory, high risk
      hematologic malignancies.
AML bears heterogeneous cells that can consequently offset killing by single-CAR-based
      therapy, which results in disease relapse. Leukemic stem cells (LSCs) associated with CLL1
      expression comprise a rare population that also plays an important role in disease
      progression and relapse for myeloid malignancies. CD33 is widely expressed in AML, high risk
      myelodysplastic syndromes (MDS) and myeloproliferative neoplasms. Targeting both CD33 and
      CLL1 surface antigens together may offer two distinct benefits. First, targeting both bulk
      disease and leukemic stem cells together allows for a more comprehensive ablation of the
      disease. Second, dual targeting of myeloid malignancies by both CD33 and CLL1 directed
      therapy overcomes the pitfalls of single-antigen therapy by preventing relapse due to antigen
      loss. While loss of a single antigen under antigen-specific selection pressure is possible,
      loss of two antigens simultaneously is much less likely.

      CLL1-CD33 cCAR is a compound Chimeric Antigen Receptor (cCAR) immunotherapy with two distinct
      functional CAR molecules expressed on a T-cell, directed against the surface proteins CLL1
      and CD33. cCAR intends to target the mechanisms of single-CAR relapse, specifically antigen
      escape and leukemic stem cells.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of participants with dose limiting toxicity (DLT) as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
time frame: 28 days
measure: Type of dose-limiting toxicity (DLT)
time frame: 28 days
measure: Number of participants with adverse event by severity as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
time frame: 2 years
measure: Overall Response Rate (ORR)
time frame: 1 year
description: Assessment of morphologic complete remission (CR), complete remission with incomplete recovery of counts (CR1), no residual disease as analyzed by flow cytometry analysis, and molecular remission by molecular studies
measure: Progression-free survival (PFS)
time frame: 1 year
measure: Overall survival
time frame: 1 year
arm group label: CLL1-CD33 cCAR T cells
arm group type: Experimental
description: CLL1-CD33cCAR T cells transduced with a lentiviral vector to express two distinct units of anti-CLL1 and CD33 CARs
intervention type: Biological
intervention name: CLL1-CD33 cCAR T cells
description: CLL1-CD33 cCAR T cells transduced with a lentiviral vector to express two distinct units of anti-CLL1 and CD33 CARs.
arm group label: CLL1-CD33 cCAR T cells
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Hongyu Zhang, MD, PhD
role: Principal Investigator
affiliation: Peking University Shenzhen Hospital
last name: Fang Liu, MD, PhD
role: Principal Investigator
affiliation: The General Hospital of Western Theater Command
last name: Kevin Pinz
phone: 6315386218
email: kevin.pinz@icellgene.com
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Not yet recruiting
contact: 
contact backup: 
country: China
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Leukemia, Myeloid
mesh term: Neoplasms
mesh term: Hematologic Neoplasms
mesh term: Leukemia, Myelogenous, Chronic, BCR-ABL Positive
mesh term: Myelodysplastic Syndromes
mesh term: Myeloproliferative Disorders
sharing ipd: No