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/NCT05991908</url>
    </required_header>
    <id_info>
      <org_study_id>MBF-FB4</org_study_id>
      <nct_id>NCT05991908</nct_id>
    </id_info>
    <brief_title>Randomized Study of Conditioning of Fludarabine Combined With Single or Dual Alkylating Agents in Myeloid Malignancies</brief_title>
    <official_title>Multiple-center Randomized Study to Compare Fludarabine and Busulfan Versus Fludarabine, Busulfan and Melphalan in Adult Patients With Acute Myeloid Leukemia (AML) and Myelodysplasia Syndrome (MDS)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Shanghai Jiao Tong University School of Medicine</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Shanghai Jiao Tong University School of Medicine</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>
    </oversight_info>
    <brief_summary>
      <textblock>
        Fludarabine and busulfan becomes standard conditioning regimen for adult patients with acute&#xD;
        myeloid leukemia (AML) or myelodysplasia syndrome (MDS). The overall relapse rate is 15~20%.&#xD;
        More recently, the investigators demonstrated that conditioning regimen with dual alkylating&#xD;
        agents consistent of fludarabine, busulfan and melphalan achieved a low incidence of relapse&#xD;
        (&lt;10%). This multiple-center randomize study is aim to compare the transplantation outcome in&#xD;
        adult patients with AML/MDS undergoing allo-HSCT with conditioning regimen of Flu-Bu4 vs.&#xD;
        FLu-Bu-Mel.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Fludarabine and busulfan was considered as myeloablative but reduced toxicity regimen and&#xD;
        became as the mainstay of conditioning regimen for adult patients with acute myeloid leukemia&#xD;
        (AML) or myelodysplasia syndrome (MDS). The disease relapse remained as major cause of&#xD;
        treatment failure. In general, the cumulated incidence of relapse (CIR) is about 15~20%&#xD;
        dependent on the risk of patients undergoing allogeneic stem cell transplantation&#xD;
        (allo-HSCT). Conditioning regimen with dual alkylating agents such as fludarabine, busulfan&#xD;
        and thiotepa (TBF) showed decreased risk of relapse in myeloid malignancies. More recently,&#xD;
        the investigators demonstrated that conditioning regimen with dual alkylating agents&#xD;
        consistent of fludarabine, busulfan and melphalan could achieve a low incidence of relapse (2&#xD;
        year CIR &lt;10%). In this multiple-center randomize study, the aim is to compare the&#xD;
        transplantation outcome in adult patients with AML/MDS undergoing allo-HSCT with conditioning&#xD;
        regimen of Flu-Bu vs. Flu-Bu-Mel.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Active, not recruiting</overall_status>
    <start_date type="Actual">August 1, 2023</start_date>
    <completion_date type="Anticipated">June 30, 2026</completion_date>
    <primary_completion_date type="Anticipated">June 30, 2025</primary_completion_date>
    <phase>Phase 3</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <intervention_model_description>study group with fludarabine, busulfan and melphalan regimen versus control group with fludarabine and busulfan</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>disease-free survival</measure>
      <time_frame>2 year</time_frame>
      <description>event defined as relapse and death of any causes</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>overall survival</measure>
      <time_frame>2 year</time_frame>
      <description>event defined as death of any causes</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>incidence of relapse</measure>
      <time_frame>2 year</time_frame>
      <description>event defined as disease relapse (bone marrow or extra medullary)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>non relapse mortality</measure>
      <time_frame>day 100</time_frame>
      <description>event defined as death without disease relapse</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>non relapse mortality</measure>
      <time_frame>2 year</time_frame>
      <description>event defined as death without disease relapse</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">222</enrollment>
    <condition>Acute Myeloid Leukemia</condition>
    <condition>Myelodysplastic Syndromes</condition>
    <arm_group>
      <arm_group_label>Flu-Bu2-Mel140</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients receive fludarabine, busulfan and melphalan as conditioning regimen</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Flu-Bu4</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Patients receive fludarabine and busulfan as conditioning regimen</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Fludarabine, busulfan and melphalan</intervention_name>
      <description>FLudarabine 150mg/m2 + Busulfan 6.4mg.kg + Mel 140mg/m2</description>
      <arm_group_label>Flu-Bu2-Mel140</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Fludarabine and Busulfan</intervention_name>
      <description>FLudarabine 150mg/m2 + Busulfan 12.8mg.kg</description>
      <arm_group_label>Flu-Bu4</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  acute myeloid leukemia (acute promyelocytic leukemia excluded) in 1st complete&#xD;
               remission&#xD;
  &#xD;
            -  myelodysplasia syndrome with bone marrow blast &gt;5% and remaining less than 20% at&#xD;
               transplantation&#xD;
  &#xD;
            -  patients with HLA matched sibling donor, 9-10 matched unrelated donor or&#xD;
               haplo-identical related donors&#xD;
  &#xD;
            -  inform consent provided&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  AML patients with active CNS or extramedullary diseases&#xD;
  &#xD;
            -  patients with active viral, bacterial or fungal infection&#xD;
  &#xD;
            -  patients with hepatitis B virus &gt;1X103 copy/ml&#xD;
  &#xD;
            -  patients with abnormal liver function, renal function, respiratory or cardiac&#xD;
               dysfunction&#xD;
  &#xD;
            -  patients with uncontrolled mental disorders&#xD;
  &#xD;
            -  patients with HIV&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>16 Years</minimum_age>
      <maximum_age>55 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Chun Wang</last_name>
      <role>Principal Investigator</role>
      <affiliation>Go Broad Health Center, Zhaxin Hospital</affiliation>
    </overall_official>
    <location>
      <facility>
        <name>Fujian Medical University Union Hospital</name>
        <address>
          <city>Fuzhou</city>
          <state>Fujian</state>
          <zip>350001</zip>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Zhongshan Hospital, Xianmen University</name>
        <address>
          <city>Xiamen</city>
          <state>Fujian</state>
          <zip>361004</zip>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>923th Hospital PLA</name>
        <address>
          <city>Nanning</city>
          <state>Guangxi</state>
          <zip>530021</zip>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>First Affiliatied Hospital of Soochow University</name>
        <address>
          <city>Suzhou</city>
          <state>Jiang Su</state>
          <zip>215006</zip>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>First Affiliated Hospital of Nanjin Medical Unviersity</name>
        <address>
          <city>Nanjin</city>
          <state>Jiangsu</state>
          <zip>210029</zip>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Ruijin Hospital</name>
        <address>
          <city>Shanghai</city>
          <state>Shanghai</state>
          <zip>200025</zip>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Shanghai No10 Hospital</name>
        <address>
          <city>Shanghai</city>
          <state>Shanghai</state>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>920th Hospital PLA</name>
        <address>
          <city>Kunming</city>
          <zip>650000</zip>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Shanghai No 6 Hospital</name>
        <address>
          <city>Shanghai</city>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 8, 2023</study_first_submitted>
    <study_first_submitted_qc>August 14, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 15, 2023</study_first_posted>
    <last_update_submitted>August 14, 2023</last_update_submitted>
    <last_update_submitted_qc>August 14, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 15, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Shanghai Jiao Tong University School of Medicine</investigator_affiliation>
      <investigator_full_name>Jiong HU</investigator_full_name>
      <investigator_title>Head, Blood &amp; Marrow Transplantation Center, Rui Jin Hospital</investigator_title>
    </responsible_party>
    <keyword>conditioning regimen, melphalan, busulfan, fludarabine</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Leukemia</mesh_term>
      <mesh_term>Leukemia, Myeloid</mesh_term>
      <mesh_term>Leukemia, Myeloid, Acute</mesh_term>
      <mesh_term>Myelodysplastic Syndromes</mesh_term>
      <mesh_term>Syndrome</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Vidarabine</mesh_term>
      <mesh_term>Fludarabine</mesh_term>
      <mesh_term>Fludarabine phosphate</mesh_term>
      <mesh_term>Melphalan</mesh_term>
      <mesh_term>Busulfan</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/NCT05991908
  org study id: MBF-FB4
  nct id: NCT05991908
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  Fludarabine and busulfan becomes standard conditioning regimen for adult patients with acute
        myeloid leukemia (AML) or myelodysplasia syndrome (MDS). The overall relapse rate is 15~20%.
        More recently, the investigators demonstrated that conditioning regimen with dual alkylating
        agents consistent of fludarabine, busulfan and melphalan achieved a low incidence of relapse
        (<10%). This multiple-center randomize study is aim to compare the transplantation outcome in
        adult patients with AML/MDS undergoing allo-HSCT with conditioning regimen of Flu-Bu4 vs.
        FLu-Bu-Mel.
  Fludarabine and busulfan was considered as myeloablative but reduced toxicity regimen and
        became as the mainstay of conditioning regimen for adult patients with acute myeloid leukemia
        (AML) or myelodysplasia syndrome (MDS). The disease relapse remained as major cause of
        treatment failure. In general, the cumulated incidence of relapse (CIR) is about 15~20%
        dependent on the risk of patients undergoing allogeneic stem cell transplantation
        (allo-HSCT). Conditioning regimen with dual alkylating agents such as fludarabine, busulfan
        and thiotepa (TBF) showed decreased risk of relapse in myeloid malignancies. More recently,
        the investigators demonstrated that conditioning regimen with dual alkylating agents
        consistent of fludarabine, busulfan and melphalan could achieve a low incidence of relapse (2
        year CIR <10%). In this multiple-center randomize study, the aim is to compare the
        transplantation outcome in adult patients with AML/MDS undergoing allo-HSCT with conditioning
        regimen of Flu-Bu vs. Flu-Bu-Mel.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: study group with fludarabine, busulfan and melphalan regimen versus control group with fludarabine and busulfan
  primary purpose: Treatment
  masking: None (Open Label)
  measure: disease-free survival
  time frame: 2 year
  description: event defined as relapse and death of any causes
  measure: overall survival
  time frame: 2 year
  description: event defined as death of any causes
  measure: incidence of relapse
  time frame: 2 year
  description: event defined as disease relapse (bone marrow or extra medullary)
  measure: non relapse mortality
  time frame: day 100
  description: event defined as death without disease relapse
  measure: non relapse mortality
  time frame: 2 year
  description: event defined as death without disease relapse
  arm group label: Flu-Bu2-Mel140
  arm group type: Experimental
  description: Patients receive fludarabine, busulfan and melphalan as conditioning regimen
  arm group label: Flu-Bu4
  arm group type: Active Comparator
  description: Patients receive fludarabine and busulfan as conditioning regimen
  intervention type: Drug
  intervention name: Fludarabine, busulfan and melphalan
  description: FLudarabine 150mg/m2 + Busulfan 6.4mg.kg + Mel 140mg/m2
  arm group label: Flu-Bu2-Mel140
  intervention type: Drug
  intervention name: Fludarabine and Busulfan
  description: FLudarabine 150mg/m2 + Busulfan 12.8mg.kg
  arm group label: Flu-Bu4
  criteria: 
  gender: All
  minimum age: 16 Years
  maximum age: 55 Years
  healthy volunteers: No
  last name: Chun Wang
  role: Principal Investigator
  affiliation: Go Broad Health Center, Zhaxin Hospital
  facility: 
  facility: 
  facility: 
  facility: 
  facility: 
  facility: 
  facility: 
  facility: 
  facility: 
  country: China
  responsible party type: Principal Investigator
  investigator affiliation: Shanghai Jiao Tong University School of Medicine
  investigator full name: Jiong HU
  investigator title: Head, Blood & Marrow Transplantation Center, Rui Jin Hospital
  mesh term: Leukemia
  mesh term: Leukemia, Myeloid
  mesh term: Leukemia, Myeloid, Acute
  mesh term: Myelodysplastic Syndromes
  mesh term: Syndrome
  mesh term: Vidarabine
  mesh term: Fludarabine
  mesh term: Fludarabine phosphate
  mesh term: Melphalan
  mesh term: Busulfan
  sharing ipd: No