<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/NCT03825731</url>
  </required_header>
  <id_info>
    <org_study_id>PGC0003</org_study_id>
    <nct_id>NCT03825731</nct_id>
  </id_info>
  <brief_title>A Study of GC022 CAR-T Cell Immunotherapy for Relapsed or Refractory B- ALL</brief_title>
  <official_title>A Study of GC022 CAR-T Cell Immunotherapy for Relapsed or Refractory B- ALL</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hebei Yanda Ludaopei Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Gracell Biotechnology Ltd.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Hebei Yanda Ludaopei Hospital</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>
      The study is an early, open, single-centered trial. The aim of this study is to evaluate the&#xD;
      safety and tolerance of GC022 CAR-T cell immunotherapy in relapsed or refractory B-ALL. The&#xD;
      investigators plan to include 20 subjects to receive GC022 therapy.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">January 17, 2019</start_date>
  <completion_date type="Anticipated">September 16, 2019</completion_date>
  <primary_completion_date type="Anticipated">September 16, 2019</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 Patients with Dose Limiting Toxicity</measure>
    <time_frame>12 weeks</time_frame>
    <description>A dose limiting toxicity is defined as any toxicity that is considered to be primarily related to the GC022 cells, which is irreversible, or life threatening or hematologic or non-hematologic Grade 3-5</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of adverse events</measure>
    <time_frame>12 weeks</time_frame>
    <description>After GC022 infusion, adverse events will be graded as CTCAE 4.0</description>
  </primary_outcome>
  <primary_outcome>
    <measure>GC022 persistence</measure>
    <time_frame>12 weeks</time_frame>
    <description>After GC022 infusion, GC022 CAR copies in peripheral blood. bone marrow and CSF will be measured by qPCR in 12 weeks</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percents of Patients with best response as complete remission and MRD negative complete remission</measure>
    <time_frame>12 weeks</time_frame>
    <description>Response rates will be estimated as the percents of patients whose best response is complete remission and MRD negative complete remission</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>B-cell Acute Lymphoblastic Leukemia</condition>
  <arm_group>
    <arm_group_label>GC022</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The patients will receive GC022 CAR-T treatment. GC022 dosage ranges from 3×10^5 to 1×10^7 CAR+T/Kg.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>GC022</intervention_name>
    <description>GC022 is a bispecific CAR-T cell immunotherapy that targeted CD19 and CD22. The subjects will receive one dose of GC022 infusion. The dosage ranges from 3×10^5 to 1×10^7 CAR+T/Kg.</description>
    <arm_group_label>GC022</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Relapsed or refractory paediatric B-cell ALL 1) 2nd or greater bone marrow (BM)&#xD;
             relapse or 2) Relapse after remission for the first time in 12 months or 3) The&#xD;
             interval between relapse after allogeneic hematopoietic stem cell transplantation and&#xD;
             CAR-T cells transfusion≥100 days or 4) Primary refractory as defined by not achieving&#xD;
             a CR after 2 cycles of a standard chemotherapy regimen or chemorefractory as defined&#xD;
             by not achieving a CR after 1 cycle of standard chemotherapy for relapsed leukaemia or&#xD;
             5) Patients with Philadelphia chromosome positive ALL were eligible if they were&#xD;
             intolerant to or had failed two lines of tyrosine kinase inhibitor (TKI) therapy, or&#xD;
             if TKI therapy was contraindicated or 6) Ineligible for allogeneic SCT because of: i.&#xD;
             Comorbid disease ii. Other contraindications to allogeneic SCT conditioning regimen&#xD;
             iii. Lack of suitable donor iv. Prior SCT v. Declined allogeneic SCT as a therapeutic&#xD;
             option after documented discussion, including expected outcomes, about the role of SCT&#xD;
             with a BM transplantation physician not part of the study team&#xD;
&#xD;
          2. For relapsed patients, CD19 tumour expression demonstrated in bone marrow or&#xD;
             peripheral blood by flow cytometry within 3 months of study entry&#xD;
&#xD;
          3. Aged 2-70 years&#xD;
&#xD;
          4. Eastern cooperative oncology group (ECOG) performance status of 0 to 2&#xD;
&#xD;
          5. Life expectancy≥12 weeks&#xD;
&#xD;
          6. Adequate organ function defined as:1) Creatinine clearance (as estimated by Cockcroft&#xD;
             Gault) &gt;60 mL/min. 2) Serum ALT/AST&lt;2.5 ULN. 3) Total bilirubin&lt;1.5 mg/dl, except in&#xD;
             subjects with Gilbert's syndrome. 4) Cardiac ejection fraction≥45%, no evidence of&#xD;
             pericardial effusion as determined by an ECHO, and no clinically significant ECG&#xD;
             findings. 5) No clinically significant pleural effusion. 6) Baseline oxygen saturation&#xD;
             &gt;92% on room air. 7) pulmonary function: ventilation function is normal or is&#xD;
             restricted mildly.&#xD;
&#xD;
          7. Females of reproductive age must be in non-lactation period. Females of childbearing&#xD;
             potential must have a negative serum or urine pregnancy test. All subjects must use&#xD;
             medical-approved-contraception (such as intrauterine device and contraceptive drugs)&#xD;
             during the period of trial and in 6 months after cell transfusion therapy.&#xD;
&#xD;
          8. The subject agree to and sign informed consent form, willing and able to comply with&#xD;
             the planned visit, research, treatment planning, laboratory and other test procedures.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Isolated extra-medullary disease relapse;&#xD;
&#xD;
          2. Patients with Burkitt's lymphoma/leukaemia;&#xD;
&#xD;
          3. Central nervous system leukemia involved CNS3;&#xD;
&#xD;
          4. Concomitant malignancy other than non-melanoma skin cancer or adequately-treated&#xD;
             cervical carcinoma in situ or prostate cancer (PSA score&lt;1.0) or adequately-treated&#xD;
             low grade bladder cancer or surgery-cured ductal carcinoma in situ or diagnosis of&#xD;
             other malignancy exceeds 5 years without relapse or treatment during the 5 years;&#xD;
&#xD;
          5. Concomitant genetic diseases except Down syndrome;&#xD;
&#xD;
          6. Any result of the following virology tests is positive: HIV; HCV; HBsAg; or HBCAb&#xD;
             positive with HBV DNA copies positive(≥ 5×10^2 copies/ml); RPR+TPPA postive;&#xD;
&#xD;
          7. Live vaccine ≤4 weeks prior to apheresis;&#xD;
&#xD;
          8. Presence of grade 2 to 4 graft-versus-host disease (GVHD) after allo-HSCT;&#xD;
&#xD;
          9. The following medications were excluded: 1) Steroids: Therapeutic systemic doses of&#xD;
             steroids must be stopped &gt;72 hours prior to tisagenlecleucel infusion. However, the&#xD;
             following physiological replacement doses of steroids are allowed: &lt;12 mg/m^2/day&#xD;
             hydrocortisone or equivalent; 2) Allogeneic cellular therapy: Any donor lymphocyte&#xD;
             infusions must be completed &gt;6 weeks prior to tisagenlecleucel infusion; 3) GVHD&#xD;
             therapies: Any systemic drug used for GVHD must be stopped &gt;4 weeks prior to infusion&#xD;
             to confirm that GVHD recurrence is not observed;&#xD;
&#xD;
         10. Preventive treatments of CNS diseases must be stopped &gt;3 days prior to infusion (e.g.,&#xD;
             intrathecal injection of methotrexate) 1) Radiotherapy of non-CNS nidus must be&#xD;
             completed &gt;2 weeks prior to infusion; 2) CNS stereotactic radiotherapy must be&#xD;
             completed &gt;8 weeks prior to infusion;&#xD;
&#xD;
         11. ≥2 grade toxicities related to previous therapy are not relieved, with the exception&#xD;
             of adverse events without security risk (e.g., alopecia);&#xD;
&#xD;
         12. Known life-threatening allergy, hypersensitivity or intolerance to GC022 cells and&#xD;
             adjuvant, including DMSO (see investigator's brochure);&#xD;
&#xD;
         13. Patients with active autoimmune disease (e.g., systemic lupus erythematosus, sjogren&#xD;
             syndrome, rheumatoid arthritis, psoriasis, multiple sclerosis, inflammatory bowel&#xD;
             disease) receive immunosuppressive therapy in 4 weeks before inclusion. thyroid&#xD;
             hormone replacement therapy is an exception;&#xD;
&#xD;
         14. For patients that underwent major surgical operation before CAR-T treatment, or&#xD;
             anticipated to undergo a major surgical operation during the study process, they need&#xD;
             to be fully recovered and clinically stable before inclusion.&#xD;
&#xD;
         15. Participate in other clinical trial and received study drugs &lt;28 days prior to&#xD;
             inclusion;&#xD;
&#xD;
         16. Concomitant disease that may or severe medical condition that may affect patients'&#xD;
             safety, including active viral or bacterial infection, uncontrollable systemic fungal&#xD;
             infection, uncontrollable cardiac disease, hypertension, abuse of psychoactive drugs,&#xD;
             et al.&#xD;
&#xD;
         17. Any other condition that may increase subjects' risk or interfere with trial's&#xD;
             results.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Hebei Yanda Ludaopei Hospital</name>
      <address>
        <city>Sanhe</city>
        <state>Hebei</state>
        <zip>065200</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Peihua Lu, PhD&amp;MD</last_name>
      <phone>+86-0316-3306393</phone>
      <email>Peihua_lu@126.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 22, 2019</study_first_submitted>
  <study_first_submitted_qc>January 30, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 31, 2019</study_first_posted>
  <last_update_submitted>January 30, 2019</last_update_submitted>
  <last_update_submitted_qc>January 30, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 31, 2019</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>Precursor Cell Lymphoblastic Leukemia-Lymphoma</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/NCT03825731
org study id: PGC0003
nct id: NCT03825731
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
The study is an early, open, single-centered trial. The aim of this study is to evaluate the
      safety and tolerance of GC022 CAR-T cell immunotherapy in relapsed or refractory B-ALL. The
      investigators plan to include 20 subjects to receive GC022 therapy.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Patients with Dose Limiting Toxicity
time frame: 12 weeks
description: A dose limiting toxicity is defined as any toxicity that is considered to be primarily related to the GC022 cells, which is irreversible, or life threatening or hematologic or non-hematologic Grade 3-5
measure: Incidence of adverse events
time frame: 12 weeks
description: After GC022 infusion, adverse events will be graded as CTCAE 4.0
measure: GC022 persistence
time frame: 12 weeks
description: After GC022 infusion, GC022 CAR copies in peripheral blood. bone marrow and CSF will be measured by qPCR in 12 weeks
measure: Percents of Patients with best response as complete remission and MRD negative complete remission
time frame: 12 weeks
description: Response rates will be estimated as the percents of patients whose best response is complete remission and MRD negative complete remission
arm group label: GC022
arm group type: Experimental
description: The patients will receive GC022 CAR-T treatment. GC022 dosage ranges from 3×10^5 to 1×10^7 CAR+T/Kg.
intervention type: Biological
intervention name: GC022
description: GC022 is a bispecific CAR-T cell immunotherapy that targeted CD19 and CD22. The subjects will receive one dose of GC022 infusion. The dosage ranges from 3×10^5 to 1×10^7 CAR+T/Kg.
arm group label: GC022
criteria: 
gender: All
minimum age: 2 Years
maximum age: 70 Years
healthy volunteers: No
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
sharing ipd: No