<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/NCT01666080</url>
  </required_header>
  <id_info>
    <org_study_id>2012OC065</org_study_id>
    <secondary_id>MT2012-11C</secondary_id>
    <nct_id>NCT01666080</nct_id>
  </id_info>
  <brief_title>Second or Greater Allogeneic Hematopoietic Stem Cell Transplant Using Reduced Intensity Conditioning (RIC)</brief_title>
  <official_title>Second or Greater Allogeneic Hematopoietic Stem Cell Transplant Using Reduced Intensity Conditioning (RIC)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Masonic Cancer Center, University of Minnesota</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Masonic Cancer Center, University of Minnesota</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a treatment guideline for a second or greater allogeneic hematopoietic stem cell&#xD;
      transplant (HSCT) using a reduced intensity conditioning (RIC) in patients with non-malignant&#xD;
      or malignant diseases. This regimen, consisting of busulfan, fludarabine, and low dose total&#xD;
      body irradiation (TBI), is designed to promote engraftment in patients who failed to achieve&#xD;
      an acceptable level of donor-derived engraftment following a previous allogeneic HCT.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      There is no research element except the collection of routine clinical data. Patients will&#xD;
      consent to allow routine clinical data to be collected and maintained in OnCore, the Masonic&#xD;
      Cancer Center's (MCC) clinical database, and specific transplant related endpoints in the&#xD;
      University Of Minnesota Blood and Bone Marrow Database as part of the historical database&#xD;
      maintained by the department.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 2012</start_date>
  <completion_date type="Anticipated">June 2024</completion_date>
  <primary_completion_date type="Anticipated">June 2024</primary_completion_date>
  <phase>N/A</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>Time to Engraftment</measure>
    <time_frame>Day 42</time_frame>
    <description>Neutrophil engraftment is defined as the first day of three consecutive days where the neutrophil count (absolute neutrophil count) is 500 cells/mm3 (0.5 x 109/L) or greater.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of Graft Failure</measure>
    <time_frame>Day 42</time_frame>
    <description>Graft failure is defined as not accepting donated cells. The donated cells do not make the new white blood cells, red blood cells and platelets.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Status of Donor Chimerism</measure>
    <time_frame>Day 100, 6 Months, 1 Year</time_frame>
    <description>A state in bone marrow transplantation in which donor hematopoietic cells and host cells exist compatibly without signs of rejection.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Acute Graft-Versus-Host Disease (GVHD)</measure>
    <time_frame>Day 100</time_frame>
    <description>Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Incidence of Chronic Graft-Versus-Host Disease (GVHD)</measure>
    <time_frame>6 Months, 1 Year</time_frame>
    <description>Chronic Graft-Versus-Host Disease is a severe long-term complication created by infusion of donor cells into a foreign host.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Transplant Related Mortality</measure>
    <time_frame>6 Months</time_frame>
    <description>In the field of transplantation, toxicity is high and all deaths without previous relapse or progression are usually considered as related to transplantation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Overall Survival</measure>
    <time_frame>6 Months</time_frame>
    <description>The percentage of people in a study or treatment group who are alive for a certain period of time after they were diagnosed with or treated for a disease. Also called survival rate.&#xD;
Overall survival will be defined as time from date of enrollment to date of death or censored at the date of last documented contact for patients still alive.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Hematologic Disorders</condition>
  <condition>Hemoglobinopathies</condition>
  <condition>Immunodeficiencies</condition>
  <arm_group>
    <arm_group_label>Reduced Intensity Conditioning</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Includes patients receiving a second or greater allogeneic hematopoietic stem cell transplant (HSCT) using reduced intensity conditioning (RIC). Patients will receive busulfan, fludarabine, total body irradiation and stem cell transplant. Keppra will be given for seizure prophylaxis.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Busulfan</intervention_name>
    <description>0.4 mg/kg (0.5 mg/kg if &lt;4 years of age) intravenously (IV) every 6 hours on Days -8 and -7.</description>
    <arm_group_label>Reduced Intensity Conditioning</arm_group_label>
    <other_name>Busulfex</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fludarabine</intervention_name>
    <description>40 mg/m^2 intravenously (IV) over 1 hour on days -6 through -2.</description>
    <arm_group_label>Reduced Intensity Conditioning</arm_group_label>
    <other_name>Fludara</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Total body irradiation</intervention_name>
    <description>200 cGy on Day -1</description>
    <arm_group_label>Reduced Intensity Conditioning</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Stem cell transplant</intervention_name>
    <description>stem cell infusion on day 0</description>
    <arm_group_label>Reduced Intensity Conditioning</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Keppra</intervention_name>
    <description>Keppra will be given for seizure prophylaxis during busulfan administration as per the standard institutional protocol.</description>
    <arm_group_label>Reduced Intensity Conditioning</arm_group_label>
    <other_name>Levetiracetam</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of any disease for which a second or greater hematopoietic stem cell&#xD;
             transplant is needed due to insufficient donor chimerism following hematopoietic&#xD;
             recovery after previous HSCT. Determination of &quot;insufficiency of donor chimerism&quot; will&#xD;
             be made by the treating transplant physician. Occasionally donor derived engraftment&#xD;
             may be present, but sustained aplasia or failed recovery of sufficient hematopoiesis&#xD;
             requires administration of a second graft. This intervention may be used for both&#xD;
             situations.&#xD;
&#xD;
          -  Donor Availability: Patients considered for transplantation must have a sufficient&#xD;
             graft as based on current criteria of the University of Minnesota Blood and Marrow&#xD;
             Transplantation Program&#xD;
&#xD;
               -  Transplantation using sufficiently matched related donors (such as matched&#xD;
                  siblings) or unrelated donors will be considered. Both granulocyte-colony&#xD;
                  stimulating factor (GCSF) stimulated peripheral blood grafts and bone marrow&#xD;
                  grafts will be considered, although bone marrow will be the priority.&#xD;
&#xD;
               -  Cord blood grafts, both related and unrelated, are also eligible. As this&#xD;
                  protocol will use a reduced intensity regimen, this protocol will use the current&#xD;
                  recommendations of the University of Minnesota for choosing cord blood grafts. If&#xD;
                  a single cord blood unit cell dose is insufficient, double cord transplantation&#xD;
                  should be considered if sufficiently matched cord blood units are available. The&#xD;
                  priority of choosing cord blood donors is based on the current institutional&#xD;
                  recommendations.&#xD;
&#xD;
               -  Exclusion of Metabolic Disorder or other Inherited Disorder Carrier Status from&#xD;
                  related donor and unrelated cord blood grafts as appropriate for primary disease.&#xD;
&#xD;
        At the discretion of the treating transplant physician, an allograft from the previous&#xD;
        donor may be used, if available.&#xD;
&#xD;
          -  Age, Performance Status, Consent&#xD;
&#xD;
               -  Age: 0 to 55 years&#xD;
&#xD;
               -  Consent: voluntary written consent (adult or parental/guardian)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous irradiation that precludes the safe administration of an additional dose of&#xD;
             200 cGy of total body irradiation (TBI). Radiation Oncology will evaluate all patients&#xD;
             who have had previous radiation therapy or TBI for approval to receive an additional&#xD;
             200 cGy of TBI&#xD;
&#xD;
          -  Pregnant or breastfeeding&#xD;
&#xD;
          -  Active, uncontrolled infection - infection that is stable or improving after 1 week of&#xD;
             appropriate therapy (4 weeks for presumed or documented fungal infections) will be&#xD;
             permitted&#xD;
&#xD;
          -  HIV positive&#xD;
&#xD;
          -  While it would be advantageous to begin therapy on this second transplant regimen &gt; 6&#xD;
             months following a prior myeloablative regimen or &gt;2 months after a reduced intensity&#xD;
             regimen, it is recognized that there are circumstances where this may not be&#xD;
             practical.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Troy Lund, M.D., Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Masonic Cancer Center, University of Minnesota</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Troy Lund, M.D., Ph.D.</last_name>
    <phone>612-625-2508</phone>
    <email>mill4991@umn.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Paul Orchard, M.D.</last_name>
    <phone>612-626-2313</phone>
    <email>orcha001@umn.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Masonic Cancer Center, University of Minnesota</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55455</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Weston P. Miller, M.D.</last_name>
      <phone>612-626-2778</phone>
      <email>mill4991@umn.eud</email>
    </contact>
    <investigator>
      <last_name>Weston P. Miller, M.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>July 31, 2012</study_first_submitted>
  <study_first_submitted_qc>August 14, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 16, 2012</study_first_posted>
  <last_update_submitted>July 6, 2023</last_update_submitted>
  <last_update_submitted_qc>July 6, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 10, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>second stem cell transplant</keyword>
  <keyword>donor hematopoietic engraftment</keyword>
  <keyword>hematopoietic stem cell transplantation</keyword>
  <keyword>inherited metabolic disorder</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hemoglobinopathies</mesh_term>
    <mesh_term>Hematologic Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fludarabine</mesh_term>
    <mesh_term>Busulfan</mesh_term>
    <mesh_term>Levetiracetam</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


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/NCT01666080
org study id: 2012OC065
secondary id: MT2012-11C
nct id: NCT01666080
lead sponsor: 
has dmc: No
This is a treatment guideline for a second or greater allogeneic hematopoietic stem cell
      transplant (HSCT) using a reduced intensity conditioning (RIC) in patients with non-malignant
      or malignant diseases. This regimen, consisting of busulfan, fludarabine, and low dose total
      body irradiation (TBI), is designed to promote engraftment in patients who failed to achieve
      an acceptable level of donor-derived engraftment following a previous allogeneic HCT.
There is no research element except the collection of routine clinical data. Patients will
      consent to allow routine clinical data to be collected and maintained in OnCore, the Masonic
      Cancer Center's (MCC) clinical database, and specific transplant related endpoints in the
      University Of Minnesota Blood and Bone Marrow Database as part of the historical database
      maintained by the department.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Time to Engraftment
time frame: Day 42
description: Neutrophil engraftment is defined as the first day of three consecutive days where the neutrophil count (absolute neutrophil count) is 500 cells/mm3 (0.5 x 109/L) or greater.
measure: Incidence of Graft Failure
time frame: Day 42
description: Graft failure is defined as not accepting donated cells. The donated cells do not make the new white blood cells, red blood cells and platelets.
measure: Status of Donor Chimerism
time frame: Day 100, 6 Months, 1 Year
description: A state in bone marrow transplantation in which donor hematopoietic cells and host cells exist compatibly without signs of rejection.
measure: Incidence of Acute Graft-Versus-Host Disease (GVHD)
time frame: Day 100
description: Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host.
measure: Change in Incidence of Chronic Graft-Versus-Host Disease (GVHD)
time frame: 6 Months, 1 Year
description: Chronic Graft-Versus-Host Disease is a severe long-term complication created by infusion of donor cells into a foreign host.
measure: Incidence of Transplant Related Mortality
time frame: 6 Months
description: In the field of transplantation, toxicity is high and all deaths without previous relapse or progression are usually considered as related to transplantation.
measure: Incidence of Overall Survival
time frame: 6 Months
description: The percentage of people in a study or treatment group who are alive for a certain period of time after they were diagnosed with or treated for a disease. Also called survival rate.
Overall survival will be defined as time from date of enrollment to date of death or censored at the date of last documented contact for patients still alive.
arm group label: Reduced Intensity Conditioning
arm group type: Other
description: Includes patients receiving a second or greater allogeneic hematopoietic stem cell transplant (HSCT) using reduced intensity conditioning (RIC). Patients will receive busulfan, fludarabine, total body irradiation and stem cell transplant. Keppra will be given for seizure prophylaxis.
intervention type: Drug
intervention name: Busulfan
description: 0.4 mg/kg (0.5 mg/kg if <4 years of age) intravenously (IV) every 6 hours on Days -8 and -7.
arm group label: Reduced Intensity Conditioning
other name: Busulfex
intervention type: Drug
intervention name: Fludarabine
description: 40 mg/m^2 intravenously (IV) over 1 hour on days -6 through -2.
arm group label: Reduced Intensity Conditioning
other name: Fludara
intervention type: Radiation
intervention name: Total body irradiation
description: 200 cGy on Day -1
arm group label: Reduced Intensity Conditioning
intervention type: Biological
intervention name: Stem cell transplant
description: stem cell infusion on day 0
arm group label: Reduced Intensity Conditioning
intervention type: Drug
intervention name: Keppra
description: Keppra will be given for seizure prophylaxis during busulfan administration as per the standard institutional protocol.
arm group label: Reduced Intensity Conditioning
other name: Levetiracetam
criteria: 
gender: All
minimum age: N/A
maximum age: 55 Years
healthy volunteers: No
last name: Troy Lund, M.D., Ph.D.
role: Principal Investigator
affiliation: Masonic Cancer Center, University of Minnesota
last name: Troy Lund, M.D., Ph.D.
phone: 612-625-2508
email: mill4991@umn.edu
last name: Paul Orchard, M.D.
phone: 612-626-2313
email: orcha001@umn.edu
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Hemoglobinopathies
mesh term: Hematologic Diseases
mesh term: Fludarabine
mesh term: Busulfan
mesh term: Levetiracetam