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/NCT06028828</url>
    </required_header>
    <id_info>
      <org_study_id>UCI 21-90 [IRB# 3095]</org_study_id>
      <secondary_id>3095</secondary_id>
      <nct_id>NCT06028828</nct_id>
    </id_info>
    <brief_title>Risk-ADAPTed Conditioning Regimen for Allogeneic Hematopoietic Stem Cell Transplantation</brief_title>
    <acronym>ADAPT</acronym>
    <official_title>Risk-ADAPTed Conditioning Regimen for Allogeneic Hematopoietic Stem Cell Transplantation (ADAPT)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of California, Irvine</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>University of California, Irvine</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>Yes</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>
        This is a prospective, single-arm, phase II study. Patients will be treated with an&#xD;
        allogeneic stem cell transplantation (AHSCT) using fludarabine, melphalan and total body&#xD;
        irradiation (TBI) conditioning with different melphalan and TBI doses based on patient- and&#xD;
        disease-related risk.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Eligible patients will receive an allogeneic stem cell transplantation using a combination of&#xD;
        fludarabine, melphalan and total body irradiation (TBI) conditioning regimen and&#xD;
        post-transplant high dose cyclophosphamide (PTCY), tacrolimus and mycophenolate mofetil (MMF)&#xD;
        for graft-versus-host prophylaxis.&#xD;
  &#xD;
        Melphalan and TBI doses will be tailored based on the Hematopoietic Stem Cell Transplant-&#xD;
        Composite Risk (HCT-CR), age and Karnofski performance status (KPS). Melphalan dose ranges&#xD;
        from 100 -140 mg/m2 while TBI dose ranges from 2-5 Gy.&#xD;
  &#xD;
        All patients will be monitored for safety and efficacy up to 2 years post-transplantation.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">September 11, 2023</start_date>
    <completion_date type="Anticipated">September 2027</completion_date>
    <primary_completion_date type="Anticipated">September 2026</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>Progression-free survival (PFS)</measure>
      <time_frame>Up to 48 months</time_frame>
      <description>PFS is defined as the time from stem cell infusion to time of disease relapse or death from any cause; data for patients who were alive without relapse will be censored at the date of last contact.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Overall survival (OS)</measure>
      <time_frame>Up to 48 months</time_frame>
      <description>OS is defined as the time from stem cell infusion until death from any cause. Data of patients who were alive without relapse will be censored at the date of last contact.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cumulative incidence of Graft-Versus-Host-Free, relapse-free survival (GRFS)</measure>
      <time_frame>Up to 48 months</time_frame>
      <description>GRFS is defined as time from stem cell infusion to time of the first event among acute GVHD grades 3-4, extensive chronic GVHD, relapse, and death. Data of patients who are event-free will be censored at the date of last contact.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cumulative incidence of relapse</measure>
      <time_frame>Up to 48 months</time_frame>
      <description>Relapse is defined as re-occurrence of the disease after stem cell infusion. Cumulative incidence of relapse will be measured from date of stem cell infusion to date of disease relapse. Death without disease relapse is considered a competing risk for relapse. Data of patients who are alive without disease relapse will be censored at the date of last contact.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cumulative incidence of Non-Relapse Mortality (NRM)</measure>
      <time_frame>Up to 48 months</time_frame>
      <description>NRM is defined as death related to AHSCT during continuous complete remission. Cumulative incidence of NRM will be measured from date of stem cell infusion to date of death. Disease relapse is considered a competing risk for NRM. Data of patients who are alive without disease relapse will be censored at the date of last contact.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cumulative incidence of acute and chronic graft versus host disease (GVHD)</measure>
      <time_frame>Up to 48 months</time_frame>
      <description>Acute and chronic GVHD will be measured from date of stem cell infusion to date of the event. Death without GVHD is considered a competing risk for GVHD. Patients who are alive without GVHD will be censored at the date of last contact.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Area Under the Curve (AUC) of Melphalan</measure>
      <time_frame>From melphalan infusion start time to 22 hours after the infusion.</time_frame>
      <description>AUC will be used to determine the pharmacokinetic of melphalan after the infusion on D-5. Data will be summarized using descriptive statistics.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">60</enrollment>
    <condition>Allogeneic Hematopoietic Stem Cell Transplantation</condition>
    <condition>Allogeneic Stem Cell Transplantation</condition>
    <condition>Hematologic Malignancies</condition>
    <arm_group>
      <arm_group_label>Patients with AML, ALL, MDS, MPN, CML, NHL, HD, CLL requiring AHSCT</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients will be treated with allogeneic stem cell transplantation (AHSCT) using fludarabine, melphalan and total body irradiation (TBI) conditioning with different melphalan and TBI doses based on their Hematopoietic Cell Transplant - Composite Risk (HCT-CR), age, and Karnofski performance status (KPS).</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Fludarabine</intervention_name>
      <description>Given Day-5, Day-4, Day-3, Day-2</description>
      <arm_group_label>Patients with AML, ALL, MDS, MPN, CML, NHL, HD, CLL requiring AHSCT</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Melphalan</intervention_name>
      <description>Given Day-5</description>
      <arm_group_label>Patients with AML, ALL, MDS, MPN, CML, NHL, HD, CLL requiring AHSCT</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Radiation</intervention_type>
      <intervention_name>Total Body Irradiation</intervention_name>
      <description>Given Day-1</description>
      <arm_group_label>Patients with AML, ALL, MDS, MPN, CML, NHL, HD, CLL requiring AHSCT</arm_group_label>
      <other_name>TBI</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Male or female aged 18-70 years&#xD;
  &#xD;
            2. Diagnosis of AML, ALL, MDS, MPN, CML, NHL, HD, CLL requiring AHSCT&#xD;
  &#xD;
            3. Has an HLA-matched related (MRD), HLA-matched unrelated (MUD), haploidentical (HAPLO)&#xD;
               or 1-Ag mismatched unrelated donor (MMUD)&#xD;
  &#xD;
            4. Karnofsky performance &gt;70%&#xD;
  &#xD;
            5. Adequate major organ system function as demonstrated by:&#xD;
  &#xD;
                 1. Serum creatinine clearance equal or more than 50 ml/min (calculated with&#xD;
                    Cockroft-Gault formula).&#xD;
  &#xD;
                 2. Bilirubin equal or less than 1.5 mg/dl except for Gilbert's disease. ALT or AST&#xD;
                    equal or less than 200 IU/ml for adults. Conjugated (direct) bilirubin less than&#xD;
                    2x upper limit of normal.&#xD;
  &#xD;
                 3. Left ventricular ejection fraction equal or greater than 40%.&#xD;
  &#xD;
                 4. Diffusing capacity for carbon monoxide (DLCO) equal or greater than 50% predicted&#xD;
                    corrected for hemoglobin.&#xD;
  &#xD;
            6. Ability to understand and the willingness to sign a written informed consent. a. Both&#xD;
               men and women and members of all races and ethnic groups are eligible for this trial.&#xD;
               Non-English speaking, deaf, hard of hearing and illiterate individuals are eligible&#xD;
               for this trial.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Inability to comply with medical recommendations or follow-up&#xD;
  &#xD;
            2. Pregnancy&#xD;
  &#xD;
            3. Active/uncontrolled bacterial or viral infection (PI is the final arbiter of this&#xD;
               criterion.)&#xD;
  &#xD;
            4. Has active CNS or ocular disease involvement within 3 months&#xD;
  &#xD;
            5. Patients with primary CNS lymphoma&#xD;
  &#xD;
            6. Patients who require modifications of the conditional regimen&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>70 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Stefan O. Ciurea, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Chao Family Comprehensive Cancer Center</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Chao Family Comprehensive Cancer Center University of California, Irvine</last_name>
      <phone>1-877-827-8839</phone>
      <email>ucstudy@uci.edu</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>University of California Irvine Medical</last_name>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Chao Family Comprehensive Cancer Center, University of California Irvine</name>
        <address>
          <city>Orange</city>
          <state>California</state>
          <zip>92868</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Stefan O Ciurea, MD</last_name>
        <phone>877-827-8839</phone>
        <email>ucstudy@uci.edu</email>
      </contact>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 31, 2023</study_first_submitted>
    <study_first_submitted_qc>August 31, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 8, 2023</study_first_posted>
    <last_update_submitted>September 14, 2023</last_update_submitted>
    <last_update_submitted_qc>September 14, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 18, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>University of California, Irvine</investigator_affiliation>
      <investigator_full_name>Stefan Octavian Ciurea</investigator_full_name>
      <investigator_title>Professor of Clinical Medicine</investigator_title>
    </responsible_party>
    <keyword>Allogeneic Hematopoietic Stem Cell Transplantation</keyword>
    <keyword>Allogeneic Stem Cell transplantation</keyword>
    <keyword>AHSCT</keyword>
    <keyword>Hematologic malignancies</keyword>
    <keyword>Melphalan</keyword>
    <keyword>Hematopoietic stem cell transplant -composite risk</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Neoplasms</mesh_term>
      <mesh_term>Hematologic Neoplasms</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Fludarabine</mesh_term>
      <mesh_term>Melphalan</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/NCT06028828
  org study id: UCI 21-90 [IRB# 3095]
  secondary id: 3095
  nct id: NCT06028828
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  is us export: No
  This is a prospective, single-arm, phase II study. Patients will be treated with an
        allogeneic stem cell transplantation (AHSCT) using fludarabine, melphalan and total body
        irradiation (TBI) conditioning with different melphalan and TBI doses based on patient- and
        disease-related risk.
  Eligible patients will receive an allogeneic stem cell transplantation using a combination of
        fludarabine, melphalan and total body irradiation (TBI) conditioning regimen and
        post-transplant high dose cyclophosphamide (PTCY), tacrolimus and mycophenolate mofetil (MMF)
        for graft-versus-host prophylaxis.
  
        Melphalan and TBI doses will be tailored based on the Hematopoietic Stem Cell Transplant-
        Composite Risk (HCT-CR), age and Karnofski performance status (KPS). Melphalan dose ranges
        from 100 -140 mg/m2 while TBI dose ranges from 2-5 Gy.
  
        All patients will be monitored for safety and efficacy up to 2 years post-transplantation.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Progression-free survival (PFS)
  time frame: Up to 48 months
  description: PFS is defined as the time from stem cell infusion to time of disease relapse or death from any cause; data for patients who were alive without relapse will be censored at the date of last contact.
  measure: Overall survival (OS)
  time frame: Up to 48 months
  description: OS is defined as the time from stem cell infusion until death from any cause. Data of patients who were alive without relapse will be censored at the date of last contact.
  measure: Cumulative incidence of Graft-Versus-Host-Free, relapse-free survival (GRFS)
  time frame: Up to 48 months
  description: GRFS is defined as time from stem cell infusion to time of the first event among acute GVHD grades 3-4, extensive chronic GVHD, relapse, and death. Data of patients who are event-free will be censored at the date of last contact.
  measure: Cumulative incidence of relapse
  time frame: Up to 48 months
  description: Relapse is defined as re-occurrence of the disease after stem cell infusion. Cumulative incidence of relapse will be measured from date of stem cell infusion to date of disease relapse. Death without disease relapse is considered a competing risk for relapse. Data of patients who are alive without disease relapse will be censored at the date of last contact.
  measure: Cumulative incidence of Non-Relapse Mortality (NRM)
  time frame: Up to 48 months
  description: NRM is defined as death related to AHSCT during continuous complete remission. Cumulative incidence of NRM will be measured from date of stem cell infusion to date of death. Disease relapse is considered a competing risk for NRM. Data of patients who are alive without disease relapse will be censored at the date of last contact.
  measure: Cumulative incidence of acute and chronic graft versus host disease (GVHD)
  time frame: Up to 48 months
  description: Acute and chronic GVHD will be measured from date of stem cell infusion to date of the event. Death without GVHD is considered a competing risk for GVHD. Patients who are alive without GVHD will be censored at the date of last contact.
  measure: Area Under the Curve (AUC) of Melphalan
  time frame: From melphalan infusion start time to 22 hours after the infusion.
  description: AUC will be used to determine the pharmacokinetic of melphalan after the infusion on D-5. Data will be summarized using descriptive statistics.
  arm group label: Patients with AML, ALL, MDS, MPN, CML, NHL, HD, CLL requiring AHSCT
  arm group type: Experimental
  description: Patients will be treated with allogeneic stem cell transplantation (AHSCT) using fludarabine, melphalan and total body irradiation (TBI) conditioning with different melphalan and TBI doses based on their Hematopoietic Cell Transplant - Composite Risk (HCT-CR), age, and Karnofski performance status (KPS).
  intervention type: Drug
  intervention name: Fludarabine
  description: Given Day-5, Day-4, Day-3, Day-2
  arm group label: Patients with AML, ALL, MDS, MPN, CML, NHL, HD, CLL requiring AHSCT
  intervention type: Drug
  intervention name: Melphalan
  description: Given Day-5
  arm group label: Patients with AML, ALL, MDS, MPN, CML, NHL, HD, CLL requiring AHSCT
  intervention type: Radiation
  intervention name: Total Body Irradiation
  description: Given Day-1
  arm group label: Patients with AML, ALL, MDS, MPN, CML, NHL, HD, CLL requiring AHSCT
  other name: TBI
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 70 Years
  healthy volunteers: No
  last name: Stefan O. Ciurea, MD
  role: Principal Investigator
  affiliation: Chao Family Comprehensive Cancer Center
  last name: Chao Family Comprehensive Cancer Center University of California, Irvine
  phone: 1-877-827-8839
  email: ucstudy@uci.edu
  last name: University of California Irvine Medical
  facility: 
  status: Recruiting
  contact: 
  country: United States
  responsible party type: Principal Investigator
  investigator affiliation: University of California, Irvine
  investigator full name: Stefan Octavian Ciurea
  investigator title: Professor of Clinical Medicine
  mesh term: Neoplasms
  mesh term: Hematologic Neoplasms
  mesh term: Fludarabine
  mesh term: Melphalan