<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/NCT04412174</url>
  </required_header>
  <id_info>
    <org_study_id>PGC011</org_study_id>
    <nct_id>NCT04412174</nct_id>
  </id_info>
  <brief_title>A Study of GC022F CAR-T Cell Immunotherapy for Relapsed or Refractory B- NHL</brief_title>
  <official_title>A Study of GC022F CAR-T Cell Immunotherapy for Relapsed or Refractory B- NHL</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>
    <has_dmc>No</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 study is an early, open, single-centered trial. The aim of this study is to evaluate the&#xD;
      safety and tolerance of GC022F CAR-T cell immunotherapy in relapsed or refractory B-NHL. The&#xD;
      investigators plan to include 18 subjects to receive GC022F therapy.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">June 2020</start_date>
  <completion_date type="Anticipated">December 2022</completion_date>
  <primary_completion_date type="Anticipated">December 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>Type and incidence of DLT, incidence and severity of treatment related AE, CRS and Neurotoxicity (Safety and tolerability)</measure>
    <time_frame>2 years</time_frame>
    <description>AE will be collected and graded according to ASTCT consensus(for Cytokine Release Syndrome, CRS and Immune Effector Cell-Associated Neurotoxicity Syndrome, ICANS) and CTCAE v5.0(for AE except CRS/ICANS)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>CAR copies of GC022F in peripheral blood, bone marrow, CSF and tumor tissue (amplification and persistence)</measure>
    <time_frame>2 years</time_frame>
    <description>GC022F CAR copies in peripheral blood, tumor tissue, bone marrow and CSF will be measured by qPCR in 2 years.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CAR cells of GC022F in peripheral blood, bone marrow and CSF (amplification and persistence)</measure>
    <time_frame>2 years</time_frame>
    <description>GC022F CAR cells in peripheral blood, bone marrow and CSF will be measured by FCM in 2 years.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate (ORR) (efficacy)</measure>
    <time_frame>3 months</time_frame>
    <description>ORR will be calculated as the percents of patients who achieved CR or PR.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR) (efficacy)</measure>
    <time_frame>2 years</time_frame>
    <description>DOR will be calculated as the time from the first assessment of CR or PR to the first assessment of relapse or death from any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-Free Survival (PFS) (efficacy)</measure>
    <time_frame>2 years</time_frame>
    <description>PFS will be calculated as the time from CAR-T infusion to disease progression or death from any cause (whichever occurs first).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS) (efficacy)</measure>
    <time_frame>2 years</time_frame>
    <description>OS will be calculated as the time from CAR-T infusion to death from any cause.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">18</enrollment>
  <condition>B-cell Non Hodgkin Lymphoma</condition>
  <arm_group>
    <arm_group_label>GC022F</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The patients will receive GC022F CAR-T treatment. GC022F dosage ranges from 3×10^5 to 1×10^6 CAR+T/Kg.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>GC022F</intervention_name>
    <description>GC022F is a bispecific CAR-T cell immunotherapy that targeted CD19 and CD22. The dosage ranges from 3×10^5 to 1×10^6 CAR+T/Kg.</description>
    <arm_group_label>GC022F</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Aged 18-70 years;&#xD;
&#xD;
          2. Relapsed or refractory B cell non-Hodgkin's lymphoma (B-NHL): 1)&#xD;
             Chemotherapy-refractory disease, defined as one or more of the following: a) No&#xD;
             response to first-line therapy (primary refractory disease, subjects who are&#xD;
             intolerant to first-line therapy chemotherapy are excluded): i. PD as the best&#xD;
             response to first-line therapy; ii.SD as the best response after at least 4 cycles of&#xD;
             first-line therapy (e.g., 4 cycles of R-CHOP) with SD duration no longer than 6 months&#xD;
             from last dose of therapy; b) No response to second or greater lines of therapy: i. PD&#xD;
             as the best response to most recent therapy regimen; ii. SD as the best response after&#xD;
             at least 2 cycles of last line of therapy with SD duration no longer than 6 months&#xD;
             from last dose of therapy; c) Refractory post-ASCT(autologous stem cell&#xD;
             transplantation): i. Disease progression or relapsed ≤12 months of ASCT (must have&#xD;
             biopsy proven recurrence in relapsed subjects); ii. If salvage therapy is given&#xD;
             post-ASCT, the subject must have had no response to or relapsed after the last line of&#xD;
             therapy; d) PD or SD as the best response after previous CAR-T therapy (at least 3&#xD;
             months ago); 2) Subjects must have received adequate prior therapy including at a&#xD;
             minimum: anti-CD20 monoclonal antibody unless investigator determines that tumor is&#xD;
             CD20 negative, and an anthracycline containing chemotherapy regimen; for subjects with&#xD;
             transformed FL must have received prior chemotherapy for follicular lymphoma and&#xD;
             subsequently have chemotherapy-refractory disease after transformation to DLBCL; 3) At&#xD;
             least 1 measurable lesion according to the Lugano Response Criteria (Cheson 2014).&#xD;
             Lesions that have been previously irradiated will be considered measurable only if&#xD;
             progression has been documented following completion of radiation therapy: a) For&#xD;
             nodular lesions, longest diameter ≥15mm, no requirement for shortest diameter; b) For&#xD;
             extranodal lesions (lesions other than lymph node and nodular lesions, including liver&#xD;
             and spleen), longest diameter ≥10mm, no requirement for shortest diameter;&#xD;
&#xD;
          3. ECOG performance status ≤2 score;&#xD;
&#xD;
          4. Life expectancy≥12 weeks;&#xD;
&#xD;
          5. CD19 and/or CD22 positive expression demonstrated in tumor tissue;&#xD;
&#xD;
          6. Adequate organ function defined as: 1) Creatinine clearance (as estimated by Cockcroft&#xD;
             Gault method)&gt;60 mL/min; for male, creatinine clearance=[&#xD;
             (140-age)×weight(kg)]/[0.818×creatinine (μmol/L)] ; for female, creatinine clearance&#xD;
             =[(140-age)×weight(kg)×0.85]/[0.818×creatinine (μmol/L)]; 2) Serum ALT/AST&lt;2.5×ULN&#xD;
             (for subjects with liver metastases, ALT/AST≤5×ULN); 3) Total bilirubin&lt;1.5×ULN (for&#xD;
             subjects with Gilbert's syndrome, total bilirubin≤ 3×ULN); 4) Left ventricular&#xD;
             ejection fraction (LVEF)&gt;50%, no evidence of clinically significant pericardial&#xD;
             effusion as determined by an ECHO; 5) No clinically significant pleural effusion; 6)&#xD;
             Baseline oxygen saturation &gt;92% on room air;&#xD;
&#xD;
          7. Females of reproductive age must be in non-lactation period. Females of childbearing&#xD;
             potential must have a negative hypersensitive serum pregnancy test. All subjects must&#xD;
             use medical-approved-contraception (such as intrauterine device and contraceptive&#xD;
             drugs) during the period of treatment and in 2 years after CAR-T infusion; males&#xD;
             should avoid sperm donation;&#xD;
&#xD;
          8. Venous access can be established, peripheral blood mononuclear cells (PBMC) can be&#xD;
             collected in researcher's judgement;&#xD;
&#xD;
          9. Agrees to sign informed consent form;&#xD;
&#xD;
         10. Be able to make good communication with researchers, willing and able to comply with&#xD;
             the planned visit, complete the research according to regulations.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Gastrointestinal involvement;&#xD;
&#xD;
          2. Active central nervous system (CNS) involvement;&#xD;
&#xD;
          3. Concomitant malignancy other than: cured non-melanoma skin cancer, cervical carcinoma&#xD;
             in situ, localized prostate cancer, superficial bladder cancer, ductal carcinoma in&#xD;
             situ, other malignancy whose disease-free survival exceeds 5 years;&#xD;
&#xD;
          4. Any result of the following virology tests is positive: HIV; HCV; HBsAg; or HBCAb&#xD;
             positive with HBV DNA copies positive; TPPA;&#xD;
&#xD;
          5. Live vaccine ≤4 weeks prior to enrollment;&#xD;
&#xD;
          6. Autologous stem cell transplantation (ASCT) ≤6 weeks prior to enrollment, history of&#xD;
             allogeneic hematopoietic stem cell transplantation (allo-HSCT);&#xD;
&#xD;
          7. Presence of complication that require systemic corticosteroids or other&#xD;
             immunosuppressive drugs therapy during the trial in researcher's judgement;&#xD;
&#xD;
          8. CNS stereotactic radiotherapy ≤4 weeks prior to enrollment;&#xD;
&#xD;
          9. Toxicities related to previous therapy did not relieved to ≤1 grade, except&#xD;
             hematological toxicity and alopecia;&#xD;
&#xD;
         10. Known life-threatening hypersensitivity to cyclophosphamide or fludarabine, or&#xD;
             presence of other intolerant conditions, or severe allergic constitution;&#xD;
&#xD;
         11. Presence of active autoimmune disease (including but not limited to, systemic lupus&#xD;
             erythematosus, sjogren syndrome, rheumatoid arthritis, psoriasis, multiple sclerosis,&#xD;
             inflammatory bowel disease, Hashimoto's thyroiditis, hypothyroidism which can be&#xD;
             controlled by thyroid hormone replacement therapy is an exception);&#xD;
&#xD;
         12. Major surgical operation that require general anesthesia happened ≤4 weeks prior to&#xD;
             enrollment, or did not be fully recovered and clinically stable prior to enrollment,&#xD;
             or be anticipated to undergo major surgical operation that require general anesthesia&#xD;
             during the study;&#xD;
&#xD;
         13. Usage of investigational drug ≤28 days prior to enrollment;&#xD;
&#xD;
         14. Any unstable cardiovascular disease happened ≤6 months prior to enrollment, including&#xD;
             but not limited to, unstable angina, myocardial infarction, heart failure (NYHA grade&#xD;
             ≥ III grade), severe arrhythmia that require drug interference, cardiac&#xD;
             angioplasty/coronary stent implantation/cardiac bypass surgery ≤6 months prior to&#xD;
             enrollment;&#xD;
&#xD;
         15. Presence of CNS disease or disease history, including epilepsy, cerebral&#xD;
             Ischemia/bleeding, dementia, cerebellar disease, any autoimmune disease that involves&#xD;
             CNS;&#xD;
&#xD;
         16. Any other condition that researcher think it is inappropriate for the subject to&#xD;
             anticipate the trial.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Peihua Lu, PhD&amp;MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hebei Yanda Ludaopei Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Peihua Lu, PhD&amp;MD</last_name>
    <phone>+86-0316-3306393</phone>
    <email>Peihua_lu@126.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Hebei Yanda Ludaopei Hospital</name>
      <address>
        <city>Sanhe</city>
        <state>Hebei</state>
        <zip>065200</zip>
        <country>China</country>
      </address>
    </facility>
    <contact>
      <last_name>Peihua Lu, PhD&amp;MD</last_name>
      <phone>+86-0316-3306393</phone>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>May 21, 2020</study_first_submitted>
  <study_first_submitted_qc>June 1, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 2, 2020</study_first_posted>
  <last_update_submitted>June 1, 2020</last_update_submitted>
  <last_update_submitted_qc>June 1, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 2, 2020</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, B-Cell</mesh_term>
  </condition_browse>
  <!-- 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/NCT04412174
org study id: PGC011
nct id: NCT04412174
lead sponsor: 
collaborator: 
has dmc: No
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 GC022F CAR-T cell immunotherapy in relapsed or refractory B-NHL. The
      investigators plan to include 18 subjects to receive GC022F therapy.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Type and incidence of DLT, incidence and severity of treatment related AE, CRS and Neurotoxicity (Safety and tolerability)
time frame: 2 years
description: AE will be collected and graded according to ASTCT consensus(for Cytokine Release Syndrome, CRS and Immune Effector Cell-Associated Neurotoxicity Syndrome, ICANS) and CTCAE v5.0(for AE except CRS/ICANS)
measure: CAR copies of GC022F in peripheral blood, bone marrow, CSF and tumor tissue (amplification and persistence)
time frame: 2 years
description: GC022F CAR copies in peripheral blood, tumor tissue, bone marrow and CSF will be measured by qPCR in 2 years.
measure: CAR cells of GC022F in peripheral blood, bone marrow and CSF (amplification and persistence)
time frame: 2 years
description: GC022F CAR cells in peripheral blood, bone marrow and CSF will be measured by FCM in 2 years.
measure: Objective response rate (ORR) (efficacy)
time frame: 3 months
description: ORR will be calculated as the percents of patients who achieved CR or PR.
measure: Duration of Response (DOR) (efficacy)
time frame: 2 years
description: DOR will be calculated as the time from the first assessment of CR or PR to the first assessment of relapse or death from any cause.
measure: Progression-Free Survival (PFS) (efficacy)
time frame: 2 years
description: PFS will be calculated as the time from CAR-T infusion to disease progression or death from any cause (whichever occurs first).
measure: Overall Survival (OS) (efficacy)
time frame: 2 years
description: OS will be calculated as the time from CAR-T infusion to death from any cause.
arm group label: GC022F
arm group type: Experimental
description: The patients will receive GC022F CAR-T treatment. GC022F dosage ranges from 3×10^5 to 1×10^6 CAR+T/Kg.
intervention type: Biological
intervention name: GC022F
description: GC022F is a bispecific CAR-T cell immunotherapy that targeted CD19 and CD22. The dosage ranges from 3×10^5 to 1×10^6 CAR+T/Kg.
arm group label: GC022F
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Peihua Lu, PhD&MD
role: Principal Investigator
affiliation: Hebei Yanda Ludaopei Hospital
last name: Peihua Lu, PhD&MD
phone: +86-0316-3306393
email: Peihua_lu@126.com
facility: 
contact: 
country: China
responsible party type: Sponsor
mesh term: Lymphoma, B-Cell