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/NCT05979363</url>
    </required_header>
    <id_info>
      <org_study_id>CAREMM-002</org_study_id>
      <nct_id>NCT05979363</nct_id>
    </id_info>
    <brief_title>A Study of Bortezomib, Lenalidomide and Dexamethasone (VRd) Followed by BCMA CAR-T Therapy in Transplant-Ineligible Patients With Primary Plasma Cell Leukemia</brief_title>
    <official_title>Safety and Efficiency of VRd Combining BCMA CAR-T Regimen for Transplant-ineligible Patients With Primary Plasma Cell Leukemia: a Prospective, Single-arm, Single-center, Phase II Study.</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Institute of Hematology &amp; Blood Diseases Hospital, China</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Institute of Hematology &amp; Blood Diseases Hospital, China</source>
    <oversight_info>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
      <is_us_export>Yes</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        This is a single-arm, open-label study to evaluate the efficacy and safety of VRD-based&#xD;
        regimen combined with BCMA CAR-T in transplant-ineligible patients with primary plasma cell&#xD;
        leukemia&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The study is a prospective, single-arm, single-centre, phase II study designed to evaluate&#xD;
        the efficacy and safety of treatment with VRD-based regimen combined with BCMA CAR-T in&#xD;
        transplant-ineligible patients with primary plasma cell leukemia. Patients received 3 courses&#xD;
        of induction therapy with VRD-based regimen followed by infusion of BCMA CAR-T cells.&#xD;
        Patients then received 3 courses of VR consolidation therapy, followed by VR maintenance&#xD;
        therapy.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">July 1, 2023</start_date>
    <completion_date type="Anticipated">July 1, 2028</completion_date>
    <primary_completion_date type="Anticipated">July 1, 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>Safety and Tolerability</measure>
      <time_frame>Up to 2 year</time_frame>
      <description>The incidence of treatment-emergent adverse events (TEAEs)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>MRD-negative rate</measure>
      <time_frame>within 1 week after consolidation treatment</time_frame>
      <description>achieving MRD-negative, as determined by NGS/NGF after consolidation treatment</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Complete response rate (CRR)</measure>
      <time_frame>within 1 week after induction therapy, 1 month after the CAR-T cell transfusion, within 1 week after consolidation therapy</time_frame>
      <description>CR or better is defined as percentage of participants who achieve a CR response or Stringent Complete Response (sCR) response accoording to the IMWG criteria</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progression free survival (PFS)</measure>
      <time_frame>Up to 2 year</time_frame>
      <description>Progression free survival is defined as the time from the date of diagnosis to the date of first documented PD, as defined in the IMWG criteria, or death due to any cause, whichever occurs first</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall Survival (OS)</measure>
      <time_frame>Up to 5 year</time_frame>
      <description>Overall survival is measured from the date of diagnosis to the date of the participant's death.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of Remission(DOR)</measure>
      <time_frame>Up to 2 year</time_frame>
      <description>Duration from the first evaluation of at least partial remission (PR) to the onset of disease progression or death due to disease progression (whichever occurs first)</description>
    </secondary_outcome>
    <other_outcome>
      <measure>The duration of CART cell in vivo</measure>
      <time_frame>Up to 1 year</time_frame>
      <description>The copies of BCMA-CART DNA in peripheral blood with qPCR method</description>
    </other_outcome>
    <other_outcome>
      <measure>Change from Baseline in Physical status assessed by International Myeloma Working Group Comprehensive Geriatric Assessment (IMWG-CGA) scores</measure>
      <time_frame>Baseline up to 5 years</time_frame>
      <description>The IMWG-CGA was calculated by combining age, activities of daily living (ADL), instrumental ADL (IADL), and Charlson Comorbidity Index (CCI), which ranges from 0 to 5 with higher scores indicating worse physical condition and greater weakness.</description>
    </other_outcome>
    <other_outcome>
      <measure>Change from Baseline in Physical status assessed by activities of daily living (ADL) scores</measure>
      <time_frame>Baseline up to 5 years</time_frame>
      <description>The ADL includes 4 items (transfer, bed mobility, toileting, and eating), which range from 0 to 6 scores. A higher score represents worse physical condition and greater weakness.</description>
    </other_outcome>
    <other_outcome>
      <measure>Change from Baseline in Physical status assessed by instrumental activities of daily living (IADL) scores</measure>
      <time_frame>Baseline up to 5 years</time_frame>
      <description>The IADL includes 5 items (cooking, cleaning, transportation, laundry, and managing finances), which range from 0 to 8 scores. A higher score represents worse physical condition and greater weakness.</description>
    </other_outcome>
    <other_outcome>
      <measure>Change from Baseline in Physical status assessed by Charlson Comorbidity Index (CCI)</measure>
      <time_frame>Baseline up to 5 years</time_frame>
      <description>The CCI estimates the number and the severity of comorbidities, including nineteen diseases with a score varying from 1 to 6 for each of them in accordance to their severity. The score can range from 0 to 37. A higher score represents more severe comorbidities.</description>
    </other_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">20</enrollment>
    <condition>Plasma Cell Leukemia</condition>
    <arm_group>
      <arm_group_label>VRD-based Regimen Combined With BCMA CART</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>VRD：Bortezomib, Lenalidomide and Dexamethasone Bortezomib SC 1.3mg/sqm on day 1,8,15,22, Lenalidomide oral 25 mg on day 1-21, and Dexamethasone 40mg on day 1,8,15,22 in a 28-day cycle.&#xD;
  Autologous BCMA-directed CAR-T cells, infusion intravenously at a target dose of 2-4 x 10^6 anti-BCMA CAR+T cells/kg.&#xD;
  Participants will receive VRD-based induction, BCMA CAR-T infusion, VR consolidation, VR maintenance.</description>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>anti-BCMA CAR-T</intervention_name>
      <description>Autologous BCMA-directed CAR-T cells, infusion intravenously at a target dose of 2.0-4.0 x 10^6 anti-BCMA CAR+T cells/kg.</description>
      <arm_group_label>VRD-based Regimen Combined With BCMA CART</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>VRD-based regimen</intervention_name>
      <description>Bortezomib, Lenalidomide and Dexamethasone</description>
      <arm_group_label>VRD-based Regimen Combined With BCMA CART</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Age ≥ 18 years and ≤ 75 years.&#xD;
  &#xD;
            2. Participants with documented primary plasma cell leukemia according to IMWG diagnostic&#xD;
               criteria (circulating plasma cells ≥5%, determined by morphology on peripheral blood&#xD;
               smear; or absolute value of peripheral blood tumorigenic plasma cells exceeds&#xD;
               2×10^9/L).&#xD;
  &#xD;
            3. Measurable disease, at screening as defined by any of the following: Serum monoclonal&#xD;
               paraprotein (M-protein) level ≥1.0 g/dL or urine M-protein level ≥200 mg/24 hours; or&#xD;
               Light chain MM without measurable disease in serum or urine: serum Ig free-light chain&#xD;
               (FLC) ≥10 mg/dL and abnormal serum Ig kappa lambda FLC ratio.&#xD;
  &#xD;
            4. Not considered for high-dose chemotherapy with Autologous Stem Cell Transplant (ASCT)&#xD;
               due to: Ineligible due to advanced age (≥65); or Ineligible evaluated by researchers;&#xD;
               or Eastern Cooperative Oncology Group Performance Status grade of 3 or 4; or Repeated&#xD;
               hematopoietic stem cell mobilization failure； or Deferral of high-dose chemotherapy&#xD;
               with ASCT as initial treatment.&#xD;
  &#xD;
            5. Bone marrow sample is confirmed as BCMA-positive by flow cytometry or pathological&#xD;
               examination.&#xD;
  &#xD;
            6. All screening blood biochemistry: tests should be performed according to the protocol&#xD;
               and within 14 days before enrollment. Screening laboratory values must meet the&#xD;
               following criteria: a.TBIL&lt;2 x upper limit of normal (ULN) (&lt;3 x ULN in patients with&#xD;
               Gilbert's syndrome); b.AST and ALT &lt;3 x ULN.; c. Creatinine clearance ≥ 30mL/min&#xD;
               (calculated using Cockroft-Gault formula).&#xD;
  &#xD;
            7. Routine blood tests (performed within 7 days, no RBC transfusion, no&#xD;
               G-CSF/GM-CSF/platelet agonists, no drug correction within 14 days before screening, no&#xD;
               PLT transfusion within 7 days) : WBC ≥ 1.5 x 109/L, ANC ≥ 1.0 x 109/L, Hb ≥ 70 g/L PLT&#xD;
               ≥ 75 x 109/L (if BMPC &lt; 50%) or PLT ≥ 50 x 109/L (if BMPC ≥ 50%).&#xD;
  &#xD;
            8. Patients must be able to take prophylactic anticoagulant therapy as recommended by the&#xD;
               study.&#xD;
  &#xD;
            9. The woman is not breastfeeding, is not pregnant and agrees not to be pregnant during&#xD;
               the study period and for the following 12 months. Male patients agreed that their&#xD;
               spouse would not become pregnant during the study period and for 12 months thereafter.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Documented active amyloidosis.&#xD;
  &#xD;
            2. Documented with central nervous system (CNS) invasion.&#xD;
  &#xD;
            3. Prior exposure to any BCMA-targeted therapy or CAR-T therapy.&#xD;
  &#xD;
            4. Patients with peripheral neuropathy greater than grade 2 or peripheral neuropathy&#xD;
               greater than grade 2 with pain at baseline, regardless of whether they were currently&#xD;
               receiving medical therapy.&#xD;
  &#xD;
            5. Known intolerance, hypersensitivity, or contraindication to glucocorticoids,&#xD;
               bortezomib, lenalidomide, and BCMA-CART cellular products.&#xD;
  &#xD;
            6. Seropositive for human immunodeficiency virus (HIV)&#xD;
  &#xD;
            7. Hepatitis B infection&#xD;
  &#xD;
            8. Hepatitis C infection&#xD;
  &#xD;
            9. Life expectancy of &lt;6 months&#xD;
  &#xD;
           10. Women who are pregnant or breastfeeding&#xD;
  &#xD;
           11. Any active gastrointestinal dysfunction that affects the patient's ability to swallow&#xD;
               tablets, or any active gastrointestinal dysfunction that may affect the absorption of&#xD;
               the studied treatment medication&#xD;
  &#xD;
           12. Subjects had major surgery within 2 weeks before randomization (for example, general&#xD;
               anesthesia), or is not fully recovered from the surgery, or surgery is arranged during&#xD;
               study period.&#xD;
  &#xD;
           13. Received live attenuated vaccine within 4 weeks prior to study treatment.&#xD;
  &#xD;
           14. According to the researcher's judgment, any condition including but not limited to&#xD;
               serious mental illness, medical illness, or other symptoms/conditions that may affect&#xD;
               study treatment, compliance, or the capability of providing informed consent.&#xD;
  &#xD;
           15. Necessary medication or supportive therapy is contraindicated with study treatment.&#xD;
  &#xD;
           16. Any diseases or complications that may interfere with the study.&#xD;
  &#xD;
           17. Patients are not willing to or cannot comply with study scheme.&#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_contact>
      <last_name>Gang An, PhD&amp;MD</last_name>
      <phone>86-022-23909171</phone>
      <email>angang@ihcams.ac.cn</email>
    </overall_contact>
    <location>
      <facility>
        <name>Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences</name>
        <address>
          <city>Tianjin</city>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Gang An, PhD&amp;MD</last_name>
        <phone>008613502181109</phone>
        <email>angang@ihcams.ac.cn</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 29, 2023</study_first_submitted>
    <study_first_submitted_qc>July 29, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 7, 2023</study_first_posted>
    <last_update_submitted>August 4, 2023</last_update_submitted>
    <last_update_submitted_qc>August 4, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 8, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Institute of Hematology &amp; Blood Diseases Hospital, China</investigator_affiliation>
      <investigator_full_name>Gang An</investigator_full_name>
      <investigator_title>Director of Myeloma center</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Leukemia</mesh_term>
      <mesh_term>Leukemia, Plasma Cell</mesh_term>
    </condition_browse>
    <!-- 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/NCT05979363
  org study id: CAREMM-002
  nct id: NCT05979363
  lead sponsor: 
  is fda regulated drug: Yes
  is fda regulated device: No
  is us export: Yes
  This is a single-arm, open-label study to evaluate the efficacy and safety of VRD-based
        regimen combined with BCMA CAR-T in transplant-ineligible patients with primary plasma cell
        leukemia
  The study is a prospective, single-arm, single-centre, phase II study designed to evaluate
        the efficacy and safety of treatment with VRD-based regimen combined with BCMA CAR-T in
        transplant-ineligible patients with primary plasma cell leukemia. Patients received 3 courses
        of induction therapy with VRD-based regimen followed by infusion of BCMA CAR-T cells.
        Patients then received 3 courses of VR consolidation therapy, followed by VR maintenance
        therapy.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Safety and Tolerability
  time frame: Up to 2 year
  description: The incidence of treatment-emergent adverse events (TEAEs)
  measure: MRD-negative rate
  time frame: within 1 week after consolidation treatment
  description: achieving MRD-negative, as determined by NGS/NGF after consolidation treatment
  measure: Complete response rate (CRR)
  time frame: within 1 week after induction therapy, 1 month after the CAR-T cell transfusion, within 1 week after consolidation therapy
  description: CR or better is defined as percentage of participants who achieve a CR response or Stringent Complete Response (sCR) response accoording to the IMWG criteria
  measure: Progression free survival (PFS)
  time frame: Up to 2 year
  description: Progression free survival is defined as the time from the date of diagnosis to the date of first documented PD, as defined in the IMWG criteria, or death due to any cause, whichever occurs first
  measure: Overall Survival (OS)
  time frame: Up to 5 year
  description: Overall survival is measured from the date of diagnosis to the date of the participant's death.
  measure: Duration of Remission(DOR)
  time frame: Up to 2 year
  description: Duration from the first evaluation of at least partial remission (PR) to the onset of disease progression or death due to disease progression (whichever occurs first)
  measure: The duration of CART cell in vivo
  time frame: Up to 1 year
  description: The copies of BCMA-CART DNA in peripheral blood with qPCR method
  measure: Change from Baseline in Physical status assessed by International Myeloma Working Group Comprehensive Geriatric Assessment (IMWG-CGA) scores
  time frame: Baseline up to 5 years
  description: The IMWG-CGA was calculated by combining age, activities of daily living (ADL), instrumental ADL (IADL), and Charlson Comorbidity Index (CCI), which ranges from 0 to 5 with higher scores indicating worse physical condition and greater weakness.
  measure: Change from Baseline in Physical status assessed by activities of daily living (ADL) scores
  time frame: Baseline up to 5 years
  description: The ADL includes 4 items (transfer, bed mobility, toileting, and eating), which range from 0 to 6 scores. A higher score represents worse physical condition and greater weakness.
  measure: Change from Baseline in Physical status assessed by instrumental activities of daily living (IADL) scores
  time frame: Baseline up to 5 years
  description: The IADL includes 5 items (cooking, cleaning, transportation, laundry, and managing finances), which range from 0 to 8 scores. A higher score represents worse physical condition and greater weakness.
  measure: Change from Baseline in Physical status assessed by Charlson Comorbidity Index (CCI)
  time frame: Baseline up to 5 years
  description: The CCI estimates the number and the severity of comorbidities, including nineteen diseases with a score varying from 1 to 6 for each of them in accordance to their severity. The score can range from 0 to 37. A higher score represents more severe comorbidities.
  arm group label: VRD-based Regimen Combined With BCMA CART
  arm group type: Experimental
  description: VRD：Bortezomib, Lenalidomide and Dexamethasone Bortezomib SC 1.3mg/sqm on day 1,8,15,22, Lenalidomide oral 25 mg on day 1-21, and Dexamethasone 40mg on day 1,8,15,22 in a 28-day cycle.
  Autologous BCMA-directed CAR-T cells, infusion intravenously at a target dose of 2-4 x 10^6 anti-BCMA CAR+T cells/kg.
  Participants will receive VRD-based induction, BCMA CAR-T infusion, VR consolidation, VR maintenance.
  intervention type: Biological
  intervention name: anti-BCMA CAR-T
  description: Autologous BCMA-directed CAR-T cells, infusion intravenously at a target dose of 2.0-4.0 x 10^6 anti-BCMA CAR+T cells/kg.
  arm group label: VRD-based Regimen Combined With BCMA CART
  intervention type: Drug
  intervention name: VRD-based regimen
  description: Bortezomib, Lenalidomide and Dexamethasone
  arm group label: VRD-based Regimen Combined With BCMA CART
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Gang An, PhD&MD
  phone: 86-022-23909171
  email: angang@ihcams.ac.cn
  facility: 
  status: Recruiting
  contact: 
  country: China
  responsible party type: Principal Investigator
  investigator affiliation: Institute of Hematology & Blood Diseases Hospital, China
  investigator full name: Gang An
  investigator title: Director of Myeloma center
  mesh term: Leukemia
  mesh term: Leukemia, Plasma Cell