<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/NCT04412889</url>
  </required_header>
  <id_info>
    <org_study_id>PGC010</org_study_id>
    <nct_id>NCT04412889</nct_id>
  </id_info>
  <brief_title>A Study of BCMA/CD19 Dual-Target CAR-T Cell Immunotherapy for Relapsed or Refractory MM</brief_title>
  <official_title>A Study of B-Cell Maturation Antigen/Cluster of Differentiation 19 Dual-Target Chimeric Antigen Receptor T Cell Immunotherapy for Relapsed or Refractory Multiple Myeloma</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 BCMA/CD19 dual-target CAR-T cell immunotherapy in relapsed or&#xD;
      refractory MM. The study will include 18 subjects to receive BCMA/CD19 dual-target CAR-T cell&#xD;
      immunotherapy.&#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 dose-limiting toxicity (DLT), incidence and severity of treatment related adverse event (AE), cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome, ICANS) (safety and tolerability)</measure>
    <time_frame>2 years</time_frame>
    <description>AE will be collected and graded according to American Society for Transplantation and Cellular Therapy (ASTCT) consensus (for CRS/ICANS) and CTCAE v5.0(for AE except CRS/ICANS)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>CAR copies in peripheral blood, bone marrow, extramedullary plasmacytoma, and cerebrospinal fluid (CSF) (amplification and persistence)</measure>
    <time_frame>2 years</time_frame>
    <description>CAR copies in peripheral blood, bone marrow, extramedullary plasmacytoma and CSF will be measured by quantitative polymerase chain reaction (qPCR) in 2 years.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CAR cells in peripheral blood, bone marrow and CSF (amplification and persistence)</measure>
    <time_frame>2 years</time_frame>
    <description>CAR cells in peripheral blood, bone marrow and CSF will be measured by flow cytometry (FCM) in 2 years.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate (ORR) (efficacy)</measure>
    <time_frame>6 months</time_frame>
    <description>ORR will be calculated as the percentage of patients who achieved partial response (PR) or better.</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 PR or better to the first assessment of progressive disease (PD) 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>
  <secondary_outcome>
    <measure>Concentration of anti-CAR antibody after infusion (humoral immune response)</measure>
    <time_frame>2 years</time_frame>
    <description>After CAR-T infusion, anti-CAR antibody in peripheral blood will be measured in 2 years</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">18</enrollment>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>CAR-T treatment group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The patients will receive BCMA/CD19 dual-target CAR-T cell treatment. BCMA/CD19 dual-target CAR-T cell dosage ranges from 2×10^5 to 1×10^6 CAR+T/Kg.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>BCMA/CD19 dual-target CAR-T cell immunotherapy</intervention_name>
    <description>The intervention is a CAR-T cell immunotherapy targeted CD19 and BCMA. The dosage ranges from 2×10^5 to 1×10^6 CAR+T/Kg.</description>
    <arm_group_label>CAR-T treatment group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Aged 18-70 years;&#xD;
&#xD;
          2. Diagnosis of relapsed or refractory multiple myeloma (MM): 1) Received at least 3&#xD;
             prior lines of treatment, including proteasome inhibitor (such as bortezomib and&#xD;
             carfilzomib) and immunomodulator (such as lenalidomide and pomalidomide), and&#xD;
             undergone at least 1 complete cycle of treatment for each line, unless PD was&#xD;
             documented as the best response to the regimen; 2) Resistant to proteasome inhibitor&#xD;
             and immunomodulator, PD in 60 days after treatment;&#xD;
&#xD;
          3. Measurable disease at screening as defined by any of the following: 1) Serum&#xD;
             monoclonal paraprotein (M-protein) level ≥10 g/L or urine M-protein level ≥200 mg/24&#xD;
             hours or; 2) Light chain MM without measurable disease in the serum or the urine:&#xD;
             serum immunoglobulin free light chain ≥10 mg/dL and abnormal serum immunoglobulin&#xD;
             kappa/lambda free light chain ratio or; 3) Plasma cell percentage in bone marrow ≥30%;&#xD;
&#xD;
          4. Histologically confirmed positive expression of CD19 and/or BCMA ≤3 months prior to&#xD;
             enrollment;&#xD;
&#xD;
          5. Eastern cooperative oncology group (ECOG) performance status of 0 to 1;&#xD;
&#xD;
          6. Life expectancy≥12 weeks;&#xD;
&#xD;
          7. Adequate organ function is defined as: 1) Hemoglobin≥6.0g/dL (did not receive red&#xD;
             blood cell transfusion ≤7 days prior to laboratory tests); 2) Platelet count&#xD;
             &gt;50×10^9/L (did not receive blood transfusion ≤7 days prior to laboratory tests); 3)&#xD;
             Absolute neutrophil count (ANC) ≥0.75×10^9/L (did not receive supportive treatment ≤7&#xD;
             days prior to laboratory tests); 4) Bilirubin &lt;2×ULN, expect for subjects with&#xD;
             congenital hyperbilirubinemia (for subjects with Gilbert's syndrome, direct&#xD;
             bilirubin≤2×ULN); 5) Creatinine clearance (according to modification of diet in renal&#xD;
             disease formulas or 24h urine collection result) ≥40 mL/min/1.73m^2; 6) Alanine&#xD;
             aminotransferase/aspartate aminotransferase (ALT/AST) &lt;2.5×ULN; 7) Corrected serum&#xD;
             calcium ≤14 mg/dL (≤3.5 mmol/L), or free calcium ion ≤6.5 mg/dL (≤1.6 mmol/L); 8)&#xD;
             Oxygen saturation &gt;92% on non-oxygen-therapy state; 9) Left ventricular ejection&#xD;
             fraction (LVEF)&gt;50%, no evidence of clinically significant pericardial effusion as&#xD;
             determined by an echocardiography;&#xD;
&#xD;
          8. Meet the requirements of peripheral blood mononuclear cells (PBMC) collection of the&#xD;
             site;&#xD;
&#xD;
          9. Females must not be in pregnancy nor in lactation. Form signing the ICF to the end of&#xD;
             the trial, females of childbearing potential and males must use efficient&#xD;
             contraception;&#xD;
&#xD;
         10. Sign the informed consent form (ICF), can understand and adhere to the procedures and&#xD;
             requirements in this study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Solitary plasmacytoma;&#xD;
&#xD;
          2. Central nervous system (CNS) involvement;&#xD;
&#xD;
          3. Previous other CAR-T or other gene-editing T cell therapy ≤8 weeks prior to enrollment&#xD;
             (not applicable to subject received CAR-T second infusion);&#xD;
&#xD;
          4. Previous allogeneic stem cell transplant; previous autologous stem cell transplant ≤12&#xD;
             weeks prior to enrollment;&#xD;
&#xD;
          5. Any result of the following virology tests is positive: HIV；HCV；HBsAg；HBcAg；TPPA;&#xD;
&#xD;
          6. Concomitant malignancy that require treatment or do not achieve complete remission in&#xD;
             3 years prior to enrollment other than: cured non-melanoma skin cancer, cervical&#xD;
             carcinoma in situ, prostate cancer that do not require treatment, other malignancy&#xD;
             whose disease-free survival exceeds 5 years;&#xD;
&#xD;
          7. Toxicities related to previous therapy did not relieved to ≤1 grade, except&#xD;
             hematological toxicity and alopecia;&#xD;
&#xD;
          8. Live vaccine ≤4 weeks prior to enrollment;&#xD;
&#xD;
          9. Other investigational drug ≤4 weeks prior to enrollment;&#xD;
&#xD;
         10. 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;
         11. 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;
         12. Presence of active autoimmune disease (including but not limited to, systemic lupus&#xD;
             erythematosus, sjogren syndrome, rheumatoid arthritis, inflammatory bowel disease,&#xD;
             hypothyroidism which can be controlled by thyroid hormone replacement therapy is an&#xD;
             exception);&#xD;
&#xD;
         13. Presence of CNS disease or disease history, including epilepsy, cerebral&#xD;
             ischemia/bleeding, dementia, cerebellar disease (not applicable to subject received&#xD;
             CAR-T second infusion, unless 4 grade ICANS happened after CAR-T first infusion);&#xD;
&#xD;
         14. Presence of complication that require systemic corticosteroids or other&#xD;
             immunosuppressive drugs therapy during the trial in researcher's judgement;&#xD;
&#xD;
         15. Known life-threatening hypersensitivity to cyclophosphamide or fludarabine, or&#xD;
             presence of other intolerant conditions, or severe allergic constitution;&#xD;
&#xD;
         16. Presence of plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome or&#xD;
             primary amyloidosis;&#xD;
&#xD;
         17. 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>
  </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>Multiple Myeloma</mesh_term>
    <mesh_term>Neoplasms, Plasma Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Immunomodulating Agents</mesh_term>
  </intervention_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/NCT04412889
org study id: PGC010
nct id: NCT04412889
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 BCMA/CD19 dual-target CAR-T cell immunotherapy in relapsed or
      refractory MM. The study will include 18 subjects to receive BCMA/CD19 dual-target CAR-T cell
      immunotherapy.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Type and incidence of dose-limiting toxicity (DLT), incidence and severity of treatment related adverse event (AE), cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome, ICANS) (safety and tolerability)
time frame: 2 years
description: AE will be collected and graded according to American Society for Transplantation and Cellular Therapy (ASTCT) consensus (for CRS/ICANS) and CTCAE v5.0(for AE except CRS/ICANS)
measure: CAR copies in peripheral blood, bone marrow, extramedullary plasmacytoma, and cerebrospinal fluid (CSF) (amplification and persistence)
time frame: 2 years
description: CAR copies in peripheral blood, bone marrow, extramedullary plasmacytoma and CSF will be measured by quantitative polymerase chain reaction (qPCR) in 2 years.
measure: CAR cells in peripheral blood, bone marrow and CSF (amplification and persistence)
time frame: 2 years
description: CAR cells in peripheral blood, bone marrow and CSF will be measured by flow cytometry (FCM) in 2 years.
measure: Objective response rate (ORR) (efficacy)
time frame: 6 months
description: ORR will be calculated as the percentage of patients who achieved partial response (PR) or better.
measure: Duration of response (DOR) (efficacy)
time frame: 2 years
description: DOR will be calculated as the time from the first assessment of PR or better to the first assessment of progressive disease (PD) 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.
measure: Concentration of anti-CAR antibody after infusion (humoral immune response)
time frame: 2 years
description: After CAR-T infusion, anti-CAR antibody in peripheral blood will be measured in 2 years
arm group label: CAR-T treatment group
arm group type: Experimental
description: The patients will receive BCMA/CD19 dual-target CAR-T cell treatment. BCMA/CD19 dual-target CAR-T cell dosage ranges from 2×10^5 to 1×10^6 CAR+T/Kg.
intervention type: Biological
intervention name: BCMA/CD19 dual-target CAR-T cell immunotherapy
description: The intervention is a CAR-T cell immunotherapy targeted CD19 and BCMA. The dosage ranges from 2×10^5 to 1×10^6 CAR+T/Kg.
arm group label: CAR-T treatment group
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: 
country: China
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Immunomodulating Agents