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/NCT05982756</url>
    </required_header>
    <id_info>
      <org_study_id>04</org_study_id>
      <nct_id>NCT05982756</nct_id>
    </id_info>
    <brief_title>Bortezomib Combined With DAG Regimen in the Treatment of Refractory/Relapsed AML</brief_title>
    <official_title>A Prospective Randomized Controlled Clinical Study of Bortezomib Combined With DAG Regimen in the Treatment of Refractory/Relapsed AML</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Zhongnan Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Zhongnan Hospital</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        In recent years, the efficacy of AML has been greatly improved, which is mainly due to the&#xD;
        following aspects: the development of individualized treatment strategies based on genetic&#xD;
        prognosis stratification, the application of high-dose cytarabine-containing induction and&#xD;
        consolidation regimens , the choice of allogeneic or autologous hematopoietic stem cell&#xD;
        transplantation, etc. However, 20%-30% of young patients and 40%-50% of elderly patients will&#xD;
        relapse again, and 20%-40% of patients cannot be relieved after standard induction regimens,&#xD;
        that is, relapsed and refractory AML. The re-induction remission rate is low, the survival&#xD;
        period is short, and the prognosis is extremely poor. There is still a lack of standard&#xD;
        treatment options. Although a small number of patients can benefit from allogeneic&#xD;
        hematopoietic stem cell transplantation (allo-HSCT), most patients lack suitable donors. The&#xD;
        choice of high-dose chemotherapy is a salvage treatment option, but treatment-related&#xD;
        hematological or non-hematological toxicities and high lethality make the option&#xD;
        controversial, especially for the elderly. The development of new low-toxic targeted drugs is&#xD;
        a future trend, and the design of new efficient and safe chemotherapy regimens is also a way&#xD;
        of thinking. This study designed a prospective single-center clinical randomized controlled&#xD;
        study plan, that is, the use of bortezomib (1.3mg/m2, d1, 4, 8, 11) combined with DAG regimen&#xD;
        in the treatment of refractory/relapsed AML, to evaluate the clinical efficacy (complete&#xD;
        remission rate , total effective rate, 2-year progression-free survival rate and 2-year&#xD;
        overall survival rate), and observe how safe the new program is. The results of the research&#xD;
        will make it possible to design a high-efficiency, low-toxicity and high-feasibility&#xD;
        chemotherapy regimen for refractory/relapsed patients, and guide the clinical treatment of&#xD;
        relapsed/refractory acute leukemia.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This study aimed to evaluate the clinical efficacy of bortezomib combined with DAG regimen in&#xD;
        the treatment of refractory and relapsed AML (complete remission rate, overall effective&#xD;
        rate, 2-year progression-free survival rate and 2-year overall survival rate), and to compare&#xD;
        the effects of the two regimens. Safety, guiding the clinical treatment of&#xD;
        relapsed/refractory acute leukemia. For the smooth development of this study, the relevant&#xD;
        monitoring indicators of the study are as follows:&#xD;
  &#xD;
          1. Select suitable subjects with relapsed/refractory acute myeloid leukemia according to&#xD;
             the inclusion criteria, and explain the treatment indications of bortezomib and the&#xD;
             purpose of this clinical study to the subjects and their families.&#xD;
  &#xD;
          2. The attending doctor communicates with the subject and his family members according to&#xD;
             the condition of the subject and signs the informed consent. The subject needs to&#xD;
             perform the following tests: three routine tests, cerebrospinal fluid routine and&#xD;
             biochemistry, liver function, kidney function, PNH test, anemia four Items (ferritin,&#xD;
             folic acid, vitamin B12, erythropoietin), blood sugar, blood lipids, electrolytes,&#xD;
             myocardial enzymes, coagulation function, HIV antibody, syphilis, screening of related&#xD;
             hepatitis virus markers, tumor markers, chest X-ray, Electrocardiogram, CT or MRI&#xD;
             examination, etc.; if conditions permit, immune function and T cell subsets can be&#xD;
             monitored.&#xD;
  &#xD;
          3. Clinical research: According to the research design, this clinical research was carried&#xD;
             out, and relevant indicators such as the incidence of third-degree and fourth-degree&#xD;
             myelosuppression and infection after chemotherapy, the rate of antibiotic use, the delay&#xD;
             rate of chemotherapy, and the extension time of chemotherapy were recorded. The&#xD;
             incidence and severity of adverse drug reactions were recorded.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">January 1, 2020</start_date>
    <completion_date type="Anticipated">December 1, 2023</completion_date>
    <primary_completion_date type="Anticipated">September 1, 2023</primary_completion_date>
    <phase>Phase 1</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Sequential Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
      <masking_description>Remove masking if necessary</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Rate Rate of bone marrow blasts</measure>
      <time_frame>Evaluation at the 4th weekend after the end of all chemotherapy cycles</time_frame>
      <description>Bone marrow blasts &lt;20%</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>blood routine</measure>
      <time_frame>Evaluation at the 4th weekend after the end of all chemotherapy cycles</time_frame>
      <description>differential blood count</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>liver function</measure>
      <time_frame>Evaluation at the 4th weekend after the end of all chemotherapy cycles</time_frame>
      <description>Detection of hepatic metabolite concentration in blood</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Recovery time</measure>
      <time_frame>Evaluation at the 4th weekend after the end of all chemotherapy cycles</time_frame>
      <description>Recovery time of patients' neutrophils, hemoglobin and platelets</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The incidence of complications in patients</measure>
      <time_frame>Evaluation at the 4th weekend after the end of all chemotherapy cycles</time_frame>
      <description>The incidence of complications in patients</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>kidney function</measure>
      <time_frame>Evaluation at the 4th weekend after the end of all chemotherapy cycles</time_frame>
      <description>Urine composition analysis</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">40</enrollment>
    <condition>Bortezomib</condition>
    <condition>Acute Myeloid Leukemia</condition>
    <arm_group>
      <arm_group_label>Test group: Induction treatment plan A</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Bortezomib+DAG pre-excitation regimen</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Control group: induction regimen B</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>DAG pre-excitation plan alone</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>DAG pre-excitation regimen with Bortezomib</intervention_name>
      <description>Bortezomib+DAG pre-excitation regimen: Bortezomib (specification 3.5mg, intravenous injection, 4 times a course of treatment, 1.3mg/m2, d1, 4, 8, 11; doxorubicin liposome injection 5 mg/ m2, intravenous infusion, once every other day, 5 times in total; cytarabine 10 mg/m2 every 12 hours, subcutaneous injection, d1-14; G-CSF 200 μg/m2 daily, subcutaneous injection, d1-14 Days, WBC &gt;10×109/L during chemotherapy, postpone the use until it falls below this value;</description>
      <arm_group_label>Control group: induction regimen B</arm_group_label>
      <arm_group_label>Test group: Induction treatment plan A</arm_group_label>
      <other_name>Bortezomib group</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Patients diagnosed with AML confirmed by bone marrow morphology and immunology&#xD;
  &#xD;
            2. Patients who do not respond or relapse after conventional treatment&#xD;
  &#xD;
            3. Age 18-75&#xD;
  &#xD;
            4. Liver and kidney function: blood bilirubin ≤ 35 μmol/L, AST/ALT below 2 times the&#xD;
               upper limit of normal value, 451 μmol/L ≥ serum creatinine ≥ 133 μmol/L, 80 ml/min ≥&#xD;
               creatinine clearance ≥ 20ml/min&#xD;
  &#xD;
            5. Cardiac function index EF value ≥ 50%&#xD;
  &#xD;
            6. Physical condition score 0-2 (ECOG score)&#xD;
  &#xD;
            7. Obtain signed informed consent from patients or family members&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Allergies or obvious contraindications to any of the drugs involved in the program&#xD;
  &#xD;
            2. Severe heart disease, including myocardial infarction and cardiac insufficiency.&#xD;
  &#xD;
            3. Suffering from other organ malignancies at the same time&#xD;
  &#xD;
            4. Active tuberculosis patients and HIV positive patients&#xD;
  &#xD;
            5. Suffering from other blood system diseases at the same time&#xD;
  &#xD;
            6. Pregnant or lactating women&#xD;
  &#xD;
            7. Inability to understand or follow the research protocol&#xD;
  &#xD;
          1. Past history of intolerance or allergy to similar drugs 2. Patients under 18 years old&#xD;
          or over 75 years old 3. Simultaneously participate in other clinical investigators 4. Any&#xD;
          other circumstances that prevent the conduct of the study&#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>Fuling Zhou, phD</last_name>
      <role>Study Director</role>
      <affiliation>Wuhan University</affiliation>
    </overall_official>
    <overall_official>
      <last_name>TIANZHI WU, phD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Wuhan University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Fuling Zhou, phD</last_name>
      <phone>+86-27-67811840</phone>
      <email>zhoufuling@whu.edu.cn</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Tianzhi Wu, phD</last_name>
      <phone>+86-27-67811840</phone>
      <email>wutianzhi@whu.edu.cn</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Zhongnan Hospital of Wuhan University</name>
        <address>
          <city>Wuhan</city>
          <state>Hubei</state>
          <zip>430071</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Zhou Fuling, director</last_name>
        <phone>+86-02767813137</phone>
        <email>zhoufuling@163.com</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>March 2023</verification_date>
    <study_first_submitted>July 13, 2023</study_first_submitted>
    <study_first_submitted_qc>July 31, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 9, 2023</study_first_posted>
    <last_update_submitted>July 31, 2023</last_update_submitted>
    <last_update_submitted_qc>July 31, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 9, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>pre-excitation regimen</keyword>
    <keyword>acute myeloid leukemi</keyword>
    <keyword>Bortezomib</keyword>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Bortezomib</mesh_term>
    </intervention_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/NCT05982756
  org study id: 04
  nct id: NCT05982756
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  In recent years, the efficacy of AML has been greatly improved, which is mainly due to the
        following aspects: the development of individualized treatment strategies based on genetic
        prognosis stratification, the application of high-dose cytarabine-containing induction and
        consolidation regimens , the choice of allogeneic or autologous hematopoietic stem cell
        transplantation, etc. However, 20%-30% of young patients and 40%-50% of elderly patients will
        relapse again, and 20%-40% of patients cannot be relieved after standard induction regimens,
        that is, relapsed and refractory AML. The re-induction remission rate is low, the survival
        period is short, and the prognosis is extremely poor. There is still a lack of standard
        treatment options. Although a small number of patients can benefit from allogeneic
        hematopoietic stem cell transplantation (allo-HSCT), most patients lack suitable donors. The
        choice of high-dose chemotherapy is a salvage treatment option, but treatment-related
        hematological or non-hematological toxicities and high lethality make the option
        controversial, especially for the elderly. The development of new low-toxic targeted drugs is
        a future trend, and the design of new efficient and safe chemotherapy regimens is also a way
        of thinking. This study designed a prospective single-center clinical randomized controlled
        study plan, that is, the use of bortezomib (1.3mg/m2, d1, 4, 8, 11) combined with DAG regimen
        in the treatment of refractory/relapsed AML, to evaluate the clinical efficacy (complete
        remission rate , total effective rate, 2-year progression-free survival rate and 2-year
        overall survival rate), and observe how safe the new program is. The results of the research
        will make it possible to design a high-efficiency, low-toxicity and high-feasibility
        chemotherapy regimen for refractory/relapsed patients, and guide the clinical treatment of
        relapsed/refractory acute leukemia.
  This study aimed to evaluate the clinical efficacy of bortezomib combined with DAG regimen in
        the treatment of refractory and relapsed AML (complete remission rate, overall effective
        rate, 2-year progression-free survival rate and 2-year overall survival rate), and to compare
        the effects of the two regimens. Safety, guiding the clinical treatment of
        relapsed/refractory acute leukemia. For the smooth development of this study, the relevant
        monitoring indicators of the study are as follows:
  
          1. Select suitable subjects with relapsed/refractory acute myeloid leukemia according to
             the inclusion criteria, and explain the treatment indications of bortezomib and the
             purpose of this clinical study to the subjects and their families.
  
          2. The attending doctor communicates with the subject and his family members according to
             the condition of the subject and signs the informed consent. The subject needs to
             perform the following tests: three routine tests, cerebrospinal fluid routine and
             biochemistry, liver function, kidney function, PNH test, anemia four Items (ferritin,
             folic acid, vitamin B12, erythropoietin), blood sugar, blood lipids, electrolytes,
             myocardial enzymes, coagulation function, HIV antibody, syphilis, screening of related
             hepatitis virus markers, tumor markers, chest X-ray, Electrocardiogram, CT or MRI
             examination, etc.; if conditions permit, immune function and T cell subsets can be
             monitored.
  
          3. Clinical research: According to the research design, this clinical research was carried
             out, and relevant indicators such as the incidence of third-degree and fourth-degree
             myelosuppression and infection after chemotherapy, the rate of antibiotic use, the delay
             rate of chemotherapy, and the extension time of chemotherapy were recorded. The
             incidence and severity of adverse drug reactions were recorded.
  allocation: Randomized
  intervention model: Sequential Assignment
  primary purpose: Treatment
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  masking description: Remove masking if necessary
  measure: Rate Rate of bone marrow blasts
  time frame: Evaluation at the 4th weekend after the end of all chemotherapy cycles
  description: Bone marrow blasts <20%
  measure: blood routine
  time frame: Evaluation at the 4th weekend after the end of all chemotherapy cycles
  description: differential blood count
  measure: liver function
  time frame: Evaluation at the 4th weekend after the end of all chemotherapy cycles
  description: Detection of hepatic metabolite concentration in blood
  measure: Recovery time
  time frame: Evaluation at the 4th weekend after the end of all chemotherapy cycles
  description: Recovery time of patients' neutrophils, hemoglobin and platelets
  measure: The incidence of complications in patients
  time frame: Evaluation at the 4th weekend after the end of all chemotherapy cycles
  description: The incidence of complications in patients
  measure: kidney function
  time frame: Evaluation at the 4th weekend after the end of all chemotherapy cycles
  description: Urine composition analysis
  arm group label: Test group: Induction treatment plan A
  arm group type: Experimental
  description: Bortezomib+DAG pre-excitation regimen
  arm group label: Control group: induction regimen B
  arm group type: Active Comparator
  description: DAG pre-excitation plan alone
  intervention type: Drug
  intervention name: DAG pre-excitation regimen with Bortezomib
  description: Bortezomib+DAG pre-excitation regimen: Bortezomib (specification 3.5mg, intravenous injection, 4 times a course of treatment, 1.3mg/m2, d1, 4, 8, 11; doxorubicin liposome injection 5 mg/ m2, intravenous infusion, once every other day, 5 times in total; cytarabine 10 mg/m2 every 12 hours, subcutaneous injection, d1-14; G-CSF 200 μg/m2 daily, subcutaneous injection, d1-14 Days, WBC >10×109/L during chemotherapy, postpone the use until it falls below this value;
  arm group label: Control group: induction regimen B
  arm group label: Test group: Induction treatment plan A
  other name: Bortezomib group
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Fuling Zhou, phD
  role: Study Director
  affiliation: Wuhan University
  last name: TIANZHI WU, phD
  role: Principal Investigator
  affiliation: Wuhan University
  last name: Fuling Zhou, phD
  phone: +86-27-67811840
  email: zhoufuling@whu.edu.cn
  last name: Tianzhi Wu, phD
  phone: +86-27-67811840
  email: wutianzhi@whu.edu.cn
  facility: 
  status: Recruiting
  contact: 
  country: China
  responsible party type: Sponsor
  mesh term: Bortezomib