<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/NCT03767725</url>
  </required_header>
  <id_info>
    <org_study_id>Weihong Chen06082018</org_study_id>
    <nct_id>NCT03767725</nct_id>
  </id_info>
  <brief_title>Anti-BCMA or/and Anti-CD19 CART Cells Treatment of Relapsed Multiple Myeloma</brief_title>
  <official_title>Phase I Trial Study of Anti-BCMA (B-cell Maturation Antigen) or/and Anti-CD19 Chimeric Antigen Receptor T Cells (CART Cell) Treatment for the Patient of Relapsed Multiple Myeloma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shenzhen Second People's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Shenzhen Second People's 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>
      This phase I trial studies the side effects and best dose of BCMA CART cells in treating&#xD;
      patients with BCMA positive multiple myeloma that have not respond to chemotherapy and&#xD;
      autologous Hematopoietic Stem Cell Transplantation (Auto-HSCT). B-cell maturation antigen&#xD;
      (BCMA), a cell surface protein expressed on mutiple maloma cells, has emerged as a very&#xD;
      selective antigen to be targeted in novel immunotherpy for MM. Targeting postulated CD19&#xD;
      positive myeloma stem cells with anti-CD19 CAR-T cells is a novel approach to MM therapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is multi-center, phase I trial that studies the side effects and best dose of BCMA CART&#xD;
      cells in treating patients with BCMA positive multiple myeloma that have not respond to&#xD;
      chemotherapy and autologous Hematopoietic Stem Cell Transplantation (Auto-HSCT). B-cell&#xD;
      maturation antigen (BCMA), a cell surface protein expressed on mutiple maloma cells , has&#xD;
      emerged as a very selective antigen to be targeted in novel immunotherpy for MM. Targeting&#xD;
      postulated CD19+ myeloma stem cells with anti-CD19 CAR-T cells is a novel approach to MM&#xD;
      therapy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">June 2, 2018</start_date>
  <completion_date type="Anticipated">September 1, 2021</completion_date>
  <primary_completion_date type="Anticipated">June 1, 2021</primary_completion_date>
  <phase>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>
    <intervention_model_description>Anti-BCMA or/and Anti-CD19 CAR Autologous T Cells</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>No Dose-limiting toxicity</measure>
    <time_frame>up to 5 mouths after T cell infusion</time_frame>
    <description>No Dose-limiting toxicity</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">10</enrollment>
  <condition>Multiple Myeloma in Relapse</condition>
  <arm_group>
    <arm_group_label>Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Phase 1 Clinical Study of The patients undergo leukapheresis. The patients then receive fludarabine and cyclophosphamide on days-5 to-3. Subjects will receive (0.6-60)x10E8 transduced CART cells as a split dose over three days as follows: Day 0, 10% fraction: (0.06-6)x10E8 CART19 cells, Day 1, 30% fraction: (0.18-18)x10E8 CART19 cells, Day 2, 60% fraction: (0.36-36)x10E8 CART19 cells.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Treatment</intervention_name>
    <description>Phase 1 Clinical Study of The patients undergo leukapheresis. The patients then receive fludarabine and cyclophosphamide on days-5 to-3. Subjects will receive (0.6-60)x10E8 transduced CART cells as a split dose over three days as follows: Day 0, 10% fraction: (0.06-6)x10E8 CART19 cells, Day 1, 30% fraction: (0.18-18)x10E8 CART19 cells, Day 2, 60% fraction: (0.36-36)x10E8 CART cells.</description>
    <arm_group_label>Treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Have the capacity to give informed consent&#xD;
&#xD;
          -  Have measurable disease by International Myeloma Working Group (IMWG) criteria based&#xD;
             on one or more of the following findings:&#xD;
&#xD;
          -  Serum M-protein &gt;= 1 g/dL&#xD;
&#xD;
          -  Urine M-protein &gt;= 200 mg/24 hour&#xD;
&#xD;
          -  Involved serum free light chain (sFLC) level &gt;= 10 mg/dL with abnormal κ/λ ratio&#xD;
&#xD;
          -  Measurable biopsy-proven plasmacytomas (&gt;= 1 lesion that has a single diameter &gt;= 2&#xD;
             cm)&#xD;
&#xD;
          -  Bone marrow plasma cells &gt;= 30%&#xD;
&#xD;
          -  Have a diagnosis of BCMA+ multiple myeloma (MM) (&gt;= 5% BCMA+ by flow cytometry on&#xD;
             CD138 co-expressing plasma cells obtained within 45 days of study enrollment); the MM&#xD;
             diagnosis must be confirmed by internal pathology review of a fresh biopsy specimen at&#xD;
             the Fred Hutchinson Cancer Research Center (FHCRC)/Seattle Cancer Care Alliance (SCCA)&#xD;
&#xD;
          -  Have relapsed or treatment refractory disease with &gt;= 10% CD138+ malignant plasma&#xD;
             cells (IHC) on bone marrow (BM) core biopsy, either:&#xD;
&#xD;
          -  Following autologous stem cell transplant (ASCT)&#xD;
&#xD;
          -  Or, if a patient has not yet undergone ASCT, the individual must:&#xD;
&#xD;
          -  Be transplant ineligible, due to age, comorbidity, patient choice, insurance reasons,&#xD;
             concerns of rapidly progressive disease, and/or discretion of attending physician,&#xD;
             and,&#xD;
&#xD;
          -  Demonstrate disease that persists after &gt; 4 cycles of induction therapy and that is&#xD;
             double refractory (persistence/progression) after therapy with both a proteasome&#xD;
             inhibitor and immunomodulatory drug (IMiD) administered either in tandem, or in&#xD;
             sequence.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Active hepatitis B, hepatitis C at the time of screening&#xD;
&#xD;
          -  Patients who are (human immunodeficiency virus [HIV]) seropositive&#xD;
&#xD;
          -  Subjects with uncontrolled systemic fungal, bacterial, viral or other infection&#xD;
             despite appropriate antibiotics or other treatment at the time of leukapheresis&#xD;
&#xD;
          -  &gt; 1 hospital admission for infection in prior 3 months&#xD;
&#xD;
          -  Presence of acute or chronic graft-versus-host disease (GVHD) unless limited to skin&#xD;
             involvement and managed with topical steroid therapy alone&#xD;
&#xD;
          -  History of any one of the following cardiovascular conditions within the past 6&#xD;
             months: class III or IV heart failure as defined by the New York Heart Association&#xD;
             (NYHA), cardiac angioplasty or stenting, myocardial infarction, unstable angina, or&#xD;
             other clinically significant cardiac disease&#xD;
&#xD;
          -  History or presence of clinically relevant central nervous system (CNS) pathology such&#xD;
             as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia,&#xD;
             Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis, active&#xD;
             central nervous system MM involvement and/or carcinomatous meningitis; subjects with&#xD;
             previously treated central nervous systems involvement may participate, provided they&#xD;
             are free of disease in the CNS (documented by flow cytometry performed on the&#xD;
             cerebrospinal fluid (CSF) within one week of enrollment) and have no evidence of new&#xD;
             sites of CNS activity&#xD;
&#xD;
          -  Pregnant or nursing women; NOTE: Women of reproductive potential must have a negative&#xD;
             serum pregnancy test performed within 48 hours of starting conditioning chemotherapy&#xD;
&#xD;
          -  Use of any of the following:&#xD;
&#xD;
          -  Therapeutic doses of corticosteroids (defined as &gt; 20 mg/day prednisone or equivalent)&#xD;
             within 7 days prior to leukapheresis; physiologic replacement, topical, and inhaled&#xD;
             steroids are permitted&#xD;
&#xD;
          -  Allogeneic hematopoietic stem cell transplant (allo-HSCT) within 90 days of&#xD;
             leukapheresis&#xD;
&#xD;
          -  Cytotoxic chemotherapeutic agents within 1 week of leukapheresis; oral&#xD;
             chemotherapeutic agents are allowed if at least 3 half-lives have elapsed prior to&#xD;
             leukapheresis&#xD;
&#xD;
          -  Low dose chemotherapy (e.g., bortezomib, lenalidomide, cyclophosphamide =&lt; 300 mg/m^2)&#xD;
             given after leukapheresis to maintain disease control must be stopped &gt;= 7 days prior&#xD;
             to initiation of lymphodepleting chemotherapy&#xD;
&#xD;
          -  Lymphotoxic chemotherapeutic agents within 2 weeks of leukapheresis&#xD;
&#xD;
          -  Experimental agents within 4 weeks of leukapheresis unless progression is documented&#xD;
             on therapy and at least 3 half-lives have elapsed prior to leukapheresis&#xD;
&#xD;
          -  Uncontrolled medical, psychological, familial, sociological, or geographical&#xD;
             conditions that do not permit compliance with the protocol, as judged by the&#xD;
             investigator; or unwillingness or inability to follow the procedures required in the&#xD;
             protocol&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &lt; 1.0×10E9/L, Hemoglobin (Hgb) &lt; 80 g/L, Platelet&#xD;
             count &lt; 50×10E9/L&#xD;
&#xD;
          -  Active autoimmune disease requiring immunosuppressive therapy&#xD;
&#xD;
          -  Major organ dysfunction defined as:&#xD;
&#xD;
          -  Creatinine clearance &lt; 20 ml/min&#xD;
&#xD;
          -  Significant hepatic dysfunction (serum glutamic-oxaloacetic transaminase [SGOT] or&#xD;
             serum glutamic-oxaloacetic transaminase (SGOT) or serum alanine aminotransferase&#xD;
             (SALT) &gt; 5×upper limit of normal; bilirubin &gt; 3.0 mg/dL)&#xD;
&#xD;
          -  Forced expiratory volume in 1 second (FEV1) of &lt; 50% predicted or diffusion capacity&#xD;
             of the lung for carbon monoxide (DLCO) (corrected) &lt; 40% (patients with clinically&#xD;
             significant pulmonary dysfunction, as determined by medical history and physical exam&#xD;
             should undergo pulmonary function testing)&#xD;
&#xD;
          -  Anticipated survival of &lt; 3 months&#xD;
&#xD;
          -  Contraindication to cyclophosphamide or fludarabine chemotherapy&#xD;
&#xD;
          -  Patients with known AL subtype amyloidosis&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>14 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Weihong Chen, M.D.</last_name>
    <phone>86-755-83366388</phone>
    <phone_ext>8199</phone_ext>
    <email>whitney-cindy@hotmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Xin Du, M.D.</last_name>
    <phone>86-755-83366388</phone>
    <phone_ext>8197</phone_ext>
    <email>duxingz@medmail.com.cn</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Shenzhen Second People's Hospital,The first affiliated hospital of Shenzhen University</name>
      <address>
        <city>Shenzhen</city>
        <state>Guangdong</state>
        <zip>518035</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Weihong Chen</last_name>
      <phone>86-755-83366388</phone>
      <phone_ext>8199</phone_ext>
      <email>whitney-cindy@hotmail.com</email>
    </contact>
    <contact_backup>
      <last_name>Xin Du</last_name>
      <phone>86-755-83366388</phone>
      <phone_ext>8197</phone_ext>
      <email>duxingz@medmail.com.cn</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>December 5, 2018</study_first_submitted>
  <study_first_submitted_qc>December 5, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 7, 2018</study_first_posted>
  <last_update_submitted>December 7, 2018</last_update_submitted>
  <last_update_submitted_qc>December 7, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 10, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Shenzhen Second People's Hospital</investigator_affiliation>
    <investigator_full_name>Wei-Hong Chen, MD</investigator_full_name>
    <investigator_title>professor, Chief physician, principal investigator</investigator_title>
  </responsible_party>
  <keyword>Anti-BCMA, Anti-CD19, CART cell, treatment, Multiple Myeloma</keyword>
  <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>
  <!-- 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/NCT03767725
org study id: Weihong Chen06082018
nct id: NCT03767725
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This phase I trial studies the side effects and best dose of BCMA CART cells in treating
      patients with BCMA positive multiple myeloma that have not respond to chemotherapy and
      autologous Hematopoietic Stem Cell Transplantation (Auto-HSCT). B-cell maturation antigen
      (BCMA), a cell surface protein expressed on mutiple maloma cells, has emerged as a very
      selective antigen to be targeted in novel immunotherpy for MM. Targeting postulated CD19
      positive myeloma stem cells with anti-CD19 CAR-T cells is a novel approach to MM therapy.
This is multi-center, phase I trial that studies the side effects and best dose of BCMA CART
      cells in treating patients with BCMA positive multiple myeloma that have not respond to
      chemotherapy and autologous Hematopoietic Stem Cell Transplantation (Auto-HSCT). B-cell
      maturation antigen (BCMA), a cell surface protein expressed on mutiple maloma cells , has
      emerged as a very selective antigen to be targeted in novel immunotherpy for MM. Targeting
      postulated CD19+ myeloma stem cells with anti-CD19 CAR-T cells is a novel approach to MM
      therapy.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Anti-BCMA or/and Anti-CD19 CAR Autologous T Cells
primary purpose: Treatment
masking: None (Open Label)
measure: No Dose-limiting toxicity
time frame: up to 5 mouths after T cell infusion
description: No Dose-limiting toxicity
arm group label: Treatment
arm group type: Experimental
description: Phase 1 Clinical Study of The patients undergo leukapheresis. The patients then receive fludarabine and cyclophosphamide on days-5 to-3. Subjects will receive (0.6-60)x10E8 transduced CART cells as a split dose over three days as follows: Day 0, 10% fraction: (0.06-6)x10E8 CART19 cells, Day 1, 30% fraction: (0.18-18)x10E8 CART19 cells, Day 2, 60% fraction: (0.36-36)x10E8 CART19 cells.
intervention type: Biological
intervention name: Treatment
description: Phase 1 Clinical Study of The patients undergo leukapheresis. The patients then receive fludarabine and cyclophosphamide on days-5 to-3. Subjects will receive (0.6-60)x10E8 transduced CART cells as a split dose over three days as follows: Day 0, 10% fraction: (0.06-6)x10E8 CART19 cells, Day 1, 30% fraction: (0.18-18)x10E8 CART19 cells, Day 2, 60% fraction: (0.36-36)x10E8 CART cells.
arm group label: Treatment
criteria: 
gender: All
minimum age: 14 Years
maximum age: 75 Years
healthy volunteers: No
last name: Weihong Chen, M.D.
phone: 86-755-83366388
phone ext: 8199
email: whitney-cindy@hotmail.com
last name: Xin Du, M.D.
phone: 86-755-83366388
phone ext: 8197
email: duxingz@medmail.com.cn
facility: 
status: Recruiting
contact: 
contact backup: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Shenzhen Second People's Hospital
investigator full name: Wei-Hong Chen, MD
investigator title: professor, Chief physician, principal investigator
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell