xml: <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/NCT05998928</url>
    </required_header>
    <id_info>
      <org_study_id>BCMA-GPRC5D CAR-T-cells</org_study_id>
      <nct_id>NCT05998928</nct_id>
    </id_info>
    <brief_title>BCMA-GPRC5D CAR-T Cells for Multiple Myeloma</brief_title>
    <official_title>Safety and Efficacy of BCMA-GPRC5D CAR-T Cells for Relapsed/Refractory Multiple Myeloma: a Single-center, Open-label, Single-arm Clinical Study</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Wuhan Union Hospital, China</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Guangzhou Bio-gene Technology Co., Ltd</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>Wuhan Union Hospital, China</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>
        This is a single-center, open-label, single-arm study to evaluate the safety and efficacy of&#xD;
        bispecific BCMA-GPRC5D Chimeric antigen receptor (CAR) T-cells in patients with relapsed or&#xD;
        refractory multiple myeloma.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        B-cell maturation antigen (BCMA)-targeted Chimeric antigen receptor (CAR) T-cell therapy has&#xD;
        yielded satisfactory clinical outcomes in patients with relapsed or refractory (R/R) multiple&#xD;
        myeloma (MM). However, BCMA-targeted CAR-T cells cannot achieve a favorable response in&#xD;
        patients with dim or negative BCMA expression on the tumor surface at baseline or relapse. G&#xD;
        protein-coupled receptor, class C, group 5, member D (GPRC5D) is highly distributed on MM&#xD;
        cells and proves to be a promising target for MM. In normal tissues, it is restrictedly&#xD;
        expressed in hair follicle, rendering it a safe target for CAR-T cell therapy as well. To&#xD;
        construct a bispecific BCMA-GPRC5D CAR structure would help mitigate the antigen escape and&#xD;
        elevates the clinical efficacy.&#xD;
  &#xD;
        This is an investigational study. The objectives are to evaluate the safety and efficacy of&#xD;
        BCMA-GPRC5D CAR-T cells in adult patients with relapsed or refractory MM disease.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">July 27, 2023</start_date>
    <completion_date type="Anticipated">July 27, 2026</completion_date>
    <primary_completion_date type="Anticipated">July 27, 2025</primary_completion_date>
    <phase>Phase 2</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>Incidence of Treatment-related Adverse Events</measure>
      <time_frame>within 2 years after infusion</time_frame>
      <description>Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome are graded by American Society for Transplantation and Cellular Therapy (ASTCT) criteria. Other therapy-related adverse events will be recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0)</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetics and pharmacodynamics - Cmax</measure>
      <time_frame>within 2 years after infusion</time_frame>
      <description>Cmax will be assessed from CAR T cell infusion to death or last follow-up (censored).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetics and pharmacodynamics - Tmax</measure>
      <time_frame>within 2 years after infusion</time_frame>
      <description>Tmax will be assessed from CAR T cell infusion to death or last follow-up (censored).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetics and pharmacodynamics - AUC 0-28d</measure>
      <time_frame>within 2 years after infusion</time_frame>
      <description>AUC 0-28d will be assessed from CAR T cell infusion to death or last follow-up (censored).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetics and pharmacodynamics - AUC 0-90d</measure>
      <time_frame>within 2 years after infusion</time_frame>
      <description>AUC 0-90d will be assessed from CAR T cell infusion to death or last follow-up (censored).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetics and pharmacodynamics - AUC 0-inf</measure>
      <time_frame>within 2 years after infusion</time_frame>
      <description>AUC 0-inf will be assessed from CAR T cell infusion to death or last follow-up (censored).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetics and pharmacodynamics - AUC 0-t1/2</measure>
      <time_frame>within 2 years after infusion</time_frame>
      <description>AUC 0-t1/2 will be assessed from CAR T cell infusion to death or last follow-up (censored).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Clinical efficacy of administering BCMA-GPRC5D CAR-T cells in Relapsed/Refractory multiple myeloma</measure>
      <time_frame>within 2 years after infusion</time_frame>
      <description>The rates of stringent complete response (sCRs), complete response (CR), very good partial response (VGPR), partial response (PR), minimal response (MR) will be assessed from CAR T cell infusion to death or last follow-up (censored).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall response rate (ORR) of administering BCMA-GPRC5D CAR-T cells in Relapsed/Refractory multiple myeloma.</measure>
      <time_frame>within 2 years after infusion</time_frame>
      <description>ORR will be assessed from CAR T cell infusion to death or last follow-up (censored).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Clinical benefit rate</measure>
      <time_frame>within 2 years after infusion</time_frame>
      <description>Clinical benefit rate refers to ORR plus MR rate.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of Response (DoR) of administering BCMA-GPRC5D CAR-T cells in Relapsed/Refractory multiple myeloma.</measure>
      <time_frame>within 2 years after infusion</time_frame>
      <description>DOR will be assessed from CAR T cell infusion to death or last follow-up (censored).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progress-free survival (PFS) of administering BCMA-GPRC5D CAR-T cells in Relapsed/Refractory multiple myeloma.</measure>
      <time_frame>within 2 years after infusion</time_frame>
      <description>PFS will be assessed from CAR T cell infusion to death or last follow-up (censored).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall survival (OS) of administering BCMA-GPRC5D CAR-T cells in Relapsed/Refractory multiple myeloma.</measure>
      <time_frame>within 2 years after infusion</time_frame>
      <description>OS will be assessed from CAR T cell infusion to death or last follow-up (censored).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Minimal Residual Disease (MRD)</measure>
      <time_frame>within 2 years after infusion</time_frame>
      <description>MRD status will be continuously monitored to assess the negative rate of MRD.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Antigen expression in tumor cells at different time points</measure>
      <time_frame>within 2 years after infusion</time_frame>
      <description>Changes in proportion of antigen-positive tumor cells after CAR T cell infusion</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">10</enrollment>
    <condition>Multiple Myeloma</condition>
    <arm_group>
      <arm_group_label>Fludarabine + Cyclophosphamide + BCMA-GPRC5D CAR-T Cells</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients will receive lymphodepletion chemotherapy with fludarabine (30 mg/m2 body surface area) plus cyclophosphamide (300 mg/m2 body surface area) for 3 consecutive days during D-7 to D-3, followed by the infusion of BCMA-GPRC5D CAR-T cells at a single dose of 4.0×10^6/kg ± 50%/kg for one day.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Fludarabine + Cyclophosphamide + BCMA-GPRC5D CAR-T Cells</intervention_name>
      <description>fludarabine 30 mg/m2 and cyclophosphamide 300 mg/m2 both on three consecutive days during D-7 to D-3&#xD;
  BCMA-GPRC5D CAR-T Cells on day 0</description>
      <arm_group_label>Fludarabine + Cyclophosphamide + BCMA-GPRC5D CAR-T Cells</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Patient or his or her legal guardian voluntarily participates in and signs an informed&#xD;
               consent form;&#xD;
  &#xD;
            2. Aged ≥ 18 years and ≤ 75 years;&#xD;
  &#xD;
            3. Diagnosed as Multiple Myeloma (MM) according to the international standard for&#xD;
               multiple myeloma (IMWG);&#xD;
  &#xD;
            4. The presence of measurable disease at screening meets one of the following&#xD;
               criteria:Serum M-protein ≥ 1.0 g/dL or Urine M-protein ≥ 200 mg/24h or diagnosed as&#xD;
               Light-chain MM without measurable disease in serum and urine; Serum free light chain ≥&#xD;
               10 mg/dL with an abnormal κ/λ ratio;&#xD;
  &#xD;
            5. Patients must relapse or be refractory after three or more lines of therapy, which at&#xD;
               least include: one Proteasome Inhibitor (PI), one Immunomodulatory Drug (IMiD), and&#xD;
               one anti-CD38 monoclonal antibody;&#xD;
  &#xD;
            6. diagnosed as relapsed/refractory disease or primary refractory disease;&#xD;
  &#xD;
            7. The last treatment is ineffective, or the disease progresses within 60 days after the&#xD;
               end of the last therapy;&#xD;
  &#xD;
            8. Patients must recover from the toxicity of the last therapy (&lt; grade 2 by CTCAE&#xD;
               criteria);&#xD;
  &#xD;
            9. ECOG score 1-2 points and the expected survival period ≥ 3 months;&#xD;
  &#xD;
           10. Liver, kidney and cardiopulmonary functions meet the following requirements:&#xD;
  &#xD;
                 1. Total bilirubin ≤ 1.5×ULN, alanine aminotransferase (ALT) ≤ 3 × ULN and aspartate&#xD;
                    aminotransferase (AST) ≤ 3 × ULN;&#xD;
  &#xD;
                 2. Serum creatinine ≤ 1.5×ULN, or creatinine clearance ≥ 60 mL/min;&#xD;
  &#xD;
                 3. Hemoglobin (Hb) ≥ 50 g/L without prior blood transfusion within 7 days;&#xD;
  &#xD;
                 4. Baseline peripheral oxygen saturation &gt; 92%;&#xD;
  &#xD;
                 5. Corrected serum calcium ≤ 12.5 mg/dL (≤ 3.1 mmol/L) or free (ionized, ionic)&#xD;
                    calcium ≤ 6.5 mg/dL (≤ 1.6 mmol/L);&#xD;
  &#xD;
                 6. Left ventricular ejection fraction (LVEF) &gt; 45%, without confirmed pericardiac&#xD;
                    effusion and abnormal electrocardiography with clinical significance;&#xD;
  &#xD;
                 7. Without clinically significant pleural effusion;&#xD;
  &#xD;
           11. Venous access could be established; without contraindications of apheresis.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Previous diagnosis and treatment of other malignancies within 3 years;&#xD;
  &#xD;
            2. Patients received previous anti-tumor therapies before apheresis including following&#xD;
               therapies: targeted therapies, epigenetics modulation drugs, other drugs or medical&#xD;
               devices (invasive) of clinical trials, monoclonal antibodies, cytotoxic agents, PIs,&#xD;
               IMiDs, radiotherapy;&#xD;
  &#xD;
            3. Central Nervous System (CNS) involvement;&#xD;
  &#xD;
            4. Patients with Fahrenheit macroglobulinemia, POEMS syndrome, or primary AL,&#xD;
               amyloidosis;&#xD;
  &#xD;
            5. Subjects with positive HBsAg or HBcAb positive and peripheral blood HBV DNA titer is&#xD;
               higher than the lower limit of detection of the research institution; HCV antibody&#xD;
               positive; HIV antibody positive; CMV DNA titer is higher than the lower limit of&#xD;
               detection of the research institution; EBV DNA titer is higher than the lower limit of&#xD;
               detection of the research institution;&#xD;
  &#xD;
            6. Patients have a severe allergic history;&#xD;
  &#xD;
            7. Patiens have severe systemic diseases or poor cardiovascular, liver, kidney functions;&#xD;
  &#xD;
            8. Acute or chronic graft versus host disease (GvHD) occurs within 6 months before the&#xD;
               screening or needs be treated with immunosuppressive agents;&#xD;
  &#xD;
            9. Active autoimmune or inflammatory diseases of the nervous system;&#xD;
  &#xD;
           10. Patients develop oncology emergencies and need to be treated before screening or&#xD;
               infusion;&#xD;
  &#xD;
           11. Uncontrolled infections that need antibiotics treatment;&#xD;
  &#xD;
           12. Exposure to hematopoietic growth factor of cells within 1-2 weeks before apheresis;&#xD;
  &#xD;
           13. Exposure to Corticosteriods or immunosuppressive agents within 2 weeks before&#xD;
               apheresis;&#xD;
  &#xD;
           14. Patients receive a major surgical operation within 4 weeks before lymphodepletion or&#xD;
               do not recover completely before the enrollment; or plan to receive a major surgical&#xD;
               operation during the study period;&#xD;
  &#xD;
           15. Live attenuated vaccine within 4 weeks before screening;&#xD;
  &#xD;
           16. Patients with severe mental illness;&#xD;
  &#xD;
           17. Patients are addcited to alcohol or drugs;&#xD;
  &#xD;
           18. Pregnant or Lactating Women; Patients and his or her spouse have a fertility plan&#xD;
               within two years after CAR-T cell infusion;&#xD;
  &#xD;
           19. Other conditions considered inappropriate by the researcher.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>75 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Heng Mei</last_name>
      <role>Principal Investigator</role>
      <affiliation>Wuhan Union Hospital, China</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Heng Mei</last_name>
      <phone>027-8572600</phone>
      <email>hmei@hust.edu.cn</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Chenggong Li</last_name>
      <phone>18108675948</phone>
      <email>chenggongli@hust.edu.cn</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Union Hospital, Tongji Medical College, Huazhong University of Science and Technology</name>
        <address>
          <city>Wuhan</city>
          <state>Hubei</state>
          <zip>430022</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Heng Mei, M.D., Ph.D</last_name>
        <email>hmei@hust.edu.cn</email>
      </contact>
      <contact_backup>
        <last_name>Chenggong Li</last_name>
        <email>chenggongli@hust.edu.cn</email>
      </contact_backup>
      <investigator>
        <last_name>Heng Mei, M.D., Ph.D</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <reference>
      <citation>Mailankody S, Devlin SM, Landa J, Nath K, Diamonte C, Carstens EJ, Russo D, Auclair R, Fitzgerald L, Cadzin B, Wang X, Sikder D, Senechal B, Bermudez VP, Purdon TJ, Hosszu K, McAvoy DP, Farzana T, Mead E, Wilcox JA, Santomasso BD, Shah GL, Shah UA, Korde N, Lesokhin A, Tan CR, Hultcrantz M, Hassoun H, Roshal M, Sen F, Dogan A, Landgren O, Giralt SA, Park JH, Usmani SZ, Riviere I, Brentjens RJ, Smith EL. GPRC5D-Targeted CAR T Cells for Myeloma. N Engl J Med. 2022 Sep 29;387(13):1196-1206. doi: 10.1056/NEJMoa2209900.</citation>
      <PMID>36170501</PMID>
    </reference>
    <reference>
      <citation>Fernandez de Larrea C, Staehr M, Lopez AV, Ng KY, Chen Y, Godfrey WD, Purdon TJ, Ponomarev V, Wendel HG, Brentjens RJ, Smith EL. Defining an Optimal Dual-Targeted CAR T-cell Therapy Approach Simultaneously Targeting BCMA and GPRC5D to Prevent BCMA Escape-Driven Relapse in Multiple Myeloma. Blood Cancer Discov. 2020 Sep;1(2):146-154. doi: 10.1158/2643-3230.BCD-20-0020.</citation>
      <PMID>33089218</PMID>
    </reference>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 28, 2023</study_first_submitted>
    <study_first_submitted_qc>August 11, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 21, 2023</study_first_posted>
    <last_update_submitted>August 11, 2023</last_update_submitted>
    <last_update_submitted_qc>August 11, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 21, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Wuhan Union Hospital, China</investigator_affiliation>
      <investigator_full_name>MEI HENG</investigator_full_name>
      <investigator_title>Proferssor, Cheif Doctor</investigator_title>
    </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>Cyclophosphamide</mesh_term>
      <mesh_term>Fludarabine</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05998928
  org study id: BCMA-GPRC5D CAR-T-cells
  nct id: NCT05998928
  lead sponsor: 
  collaborator: 
  is fda regulated drug: No
  is fda regulated device: No
  This is a single-center, open-label, single-arm study to evaluate the safety and efficacy of
        bispecific BCMA-GPRC5D Chimeric antigen receptor (CAR) T-cells in patients with relapsed or
        refractory multiple myeloma.
  B-cell maturation antigen (BCMA)-targeted Chimeric antigen receptor (CAR) T-cell therapy has
        yielded satisfactory clinical outcomes in patients with relapsed or refractory (R/R) multiple
        myeloma (MM). However, BCMA-targeted CAR-T cells cannot achieve a favorable response in
        patients with dim or negative BCMA expression on the tumor surface at baseline or relapse. G
        protein-coupled receptor, class C, group 5, member D (GPRC5D) is highly distributed on MM
        cells and proves to be a promising target for MM. In normal tissues, it is restrictedly
        expressed in hair follicle, rendering it a safe target for CAR-T cell therapy as well. To
        construct a bispecific BCMA-GPRC5D CAR structure would help mitigate the antigen escape and
        elevates the clinical efficacy.
  
        This is an investigational study. The objectives are to evaluate the safety and efficacy of
        BCMA-GPRC5D CAR-T cells in adult patients with relapsed or refractory MM disease.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Incidence of Treatment-related Adverse Events
  time frame: within 2 years after infusion
  description: Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome are graded by American Society for Transplantation and Cellular Therapy (ASTCT) criteria. Other therapy-related adverse events will be recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0)
  measure: Pharmacokinetics and pharmacodynamics - Cmax
  time frame: within 2 years after infusion
  description: Cmax will be assessed from CAR T cell infusion to death or last follow-up (censored).
  measure: Pharmacokinetics and pharmacodynamics - Tmax
  time frame: within 2 years after infusion
  description: Tmax will be assessed from CAR T cell infusion to death or last follow-up (censored).
  measure: Pharmacokinetics and pharmacodynamics - AUC 0-28d
  time frame: within 2 years after infusion
  description: AUC 0-28d will be assessed from CAR T cell infusion to death or last follow-up (censored).
  measure: Pharmacokinetics and pharmacodynamics - AUC 0-90d
  time frame: within 2 years after infusion
  description: AUC 0-90d will be assessed from CAR T cell infusion to death or last follow-up (censored).
  measure: Pharmacokinetics and pharmacodynamics - AUC 0-inf
  time frame: within 2 years after infusion
  description: AUC 0-inf will be assessed from CAR T cell infusion to death or last follow-up (censored).
  measure: Pharmacokinetics and pharmacodynamics - AUC 0-t1/2
  time frame: within 2 years after infusion
  description: AUC 0-t1/2 will be assessed from CAR T cell infusion to death or last follow-up (censored).
  measure: Clinical efficacy of administering BCMA-GPRC5D CAR-T cells in Relapsed/Refractory multiple myeloma
  time frame: within 2 years after infusion
  description: The rates of stringent complete response (sCRs), complete response (CR), very good partial response (VGPR), partial response (PR), minimal response (MR) will be assessed from CAR T cell infusion to death or last follow-up (censored).
  measure: Overall response rate (ORR) of administering BCMA-GPRC5D CAR-T cells in Relapsed/Refractory multiple myeloma.
  time frame: within 2 years after infusion
  description: ORR will be assessed from CAR T cell infusion to death or last follow-up (censored).
  measure: Clinical benefit rate
  time frame: within 2 years after infusion
  description: Clinical benefit rate refers to ORR plus MR rate.
  measure: Duration of Response (DoR) of administering BCMA-GPRC5D CAR-T cells in Relapsed/Refractory multiple myeloma.
  time frame: within 2 years after infusion
  description: DOR will be assessed from CAR T cell infusion to death or last follow-up (censored).
  measure: Progress-free survival (PFS) of administering BCMA-GPRC5D CAR-T cells in Relapsed/Refractory multiple myeloma.
  time frame: within 2 years after infusion
  description: PFS will be assessed from CAR T cell infusion to death or last follow-up (censored).
  measure: Overall survival (OS) of administering BCMA-GPRC5D CAR-T cells in Relapsed/Refractory multiple myeloma.
  time frame: within 2 years after infusion
  description: OS will be assessed from CAR T cell infusion to death or last follow-up (censored).
  measure: Minimal Residual Disease (MRD)
  time frame: within 2 years after infusion
  description: MRD status will be continuously monitored to assess the negative rate of MRD.
  measure: Antigen expression in tumor cells at different time points
  time frame: within 2 years after infusion
  description: Changes in proportion of antigen-positive tumor cells after CAR T cell infusion
  arm group label: Fludarabine + Cyclophosphamide + BCMA-GPRC5D CAR-T Cells
  arm group type: Experimental
  description: Patients will receive lymphodepletion chemotherapy with fludarabine (30 mg/m2 body surface area) plus cyclophosphamide (300 mg/m2 body surface area) for 3 consecutive days during D-7 to D-3, followed by the infusion of BCMA-GPRC5D CAR-T cells at a single dose of 4.0×10^6/kg ± 50%/kg for one day.
  intervention type: Drug
  intervention name: Fludarabine + Cyclophosphamide + BCMA-GPRC5D CAR-T Cells
  description: fludarabine 30 mg/m2 and cyclophosphamide 300 mg/m2 both on three consecutive days during D-7 to D-3
  BCMA-GPRC5D CAR-T Cells on day 0
  arm group label: Fludarabine + Cyclophosphamide + BCMA-GPRC5D CAR-T Cells
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Heng Mei
  role: Principal Investigator
  affiliation: Wuhan Union Hospital, China
  last name: Heng Mei
  phone: 027-8572600
  email: hmei@hust.edu.cn
  last name: Chenggong Li
  phone: 18108675948
  email: chenggongli@hust.edu.cn
  facility: 
  status: Recruiting
  contact: 
  contact backup: 
  investigator: 
  country: China
  citation: Mailankody S, Devlin SM, Landa J, Nath K, Diamonte C, Carstens EJ, Russo D, Auclair R, Fitzgerald L, Cadzin B, Wang X, Sikder D, Senechal B, Bermudez VP, Purdon TJ, Hosszu K, McAvoy DP, Farzana T, Mead E, Wilcox JA, Santomasso BD, Shah GL, Shah UA, Korde N, Lesokhin A, Tan CR, Hultcrantz M, Hassoun H, Roshal M, Sen F, Dogan A, Landgren O, Giralt SA, Park JH, Usmani SZ, Riviere I, Brentjens RJ, Smith EL. GPRC5D-Targeted CAR T Cells for Myeloma. N Engl J Med. 2022 Sep 29;387(13):1196-1206. doi: 10.1056/NEJMoa2209900.
  PMID: 36170501
  citation: Fernandez de Larrea C, Staehr M, Lopez AV, Ng KY, Chen Y, Godfrey WD, Purdon TJ, Ponomarev V, Wendel HG, Brentjens RJ, Smith EL. Defining an Optimal Dual-Targeted CAR T-cell Therapy Approach Simultaneously Targeting BCMA and GPRC5D to Prevent BCMA Escape-Driven Relapse in Multiple Myeloma. Blood Cancer Discov. 2020 Sep;1(2):146-154. doi: 10.1158/2643-3230.BCD-20-0020.
  PMID: 33089218
  responsible party type: Principal Investigator
  investigator affiliation: Wuhan Union Hospital, China
  investigator full name: MEI HENG
  investigator title: Proferssor, Cheif Doctor
  mesh term: Multiple Myeloma
  mesh term: Neoplasms, Plasma Cell
  mesh term: Cyclophosphamide
  mesh term: Fludarabine
  sharing ipd: No