<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/NCT03303950</url>
  </required_header>
  <id_info>
    <org_study_id>HCI98381</org_study_id>
    <nct_id>NCT03303950</nct_id>
  </id_info>
  <brief_title>Allogeneic Stem Cell Transplantation for Multiple Myeloma and Myelofibrosis</brief_title>
  <official_title>Busulfan, Fludarabine, Donor Stem Cell Transplant, and Cyclophosphamide in Treating Participants With Multiple Myeloma or Myelofibrosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Utah</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Utah</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 phase II trial studies how well busulfan, fludarabine, donor stem cell transplant, and&#xD;
      cyclophosphamide in treating participants with multiple myeloma or myelofibrosis. Drugs used&#xD;
      in chemotherapy, such as busulfan, fludarabine, and cyclophosphamide, work in different ways&#xD;
      to stop the growth of cancer cells, either by killing the cells, by stopping them from&#xD;
      dividing, or by stopping them from spreading. Giving chemotherapy before a donor stem cell&#xD;
      transplant helps stop the growth of cells in the bone marrow, including normal blood-forming&#xD;
      cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused&#xD;
      into the participant they may help the participant's bone marrow make stem cells, red blood&#xD;
      cells, white blood cells, and platelets. Giving busulfan and fludarabine before and&#xD;
      cyclophosphamide after donor stem cell may work better in treating participants with multiple&#xD;
      myeloma or myelofibrosis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To evaluate non-relapse mortality (NRM) up to day +100.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To evaluate non-relapse mortality (NRM) up to day +365. II. To evaluate the incidence of&#xD;
      acute graft versus host disease (GVHD) and chronic GVHD up to day +365 post-transplant.&#xD;
&#xD;
      III. To evaluate the overall survival and disease free survival up to 1 year. IV. To evaluate&#xD;
      clinical response and molecular response (complete response and partial response) up to 1&#xD;
      year.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Participants receive busulfan intravenously (IV) over 2 hours and fludarabine IV over 30&#xD;
      minutes on days -5 to -2. Participants undergo hematopoietic cell transplantation (HSCT) on&#xD;
      day 0. Participants then receive cyclophosphamide IV over 60 minutes on days 3 and 4.&#xD;
&#xD;
      After completion of study treatment, participants are followed up for 1 year.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Slow accrual&#xD;
  </why_stopped>
  <start_date type="Actual">March 30, 2018</start_date>
  <completion_date type="Actual">February 19, 2020</completion_date>
  <primary_completion_date type="Actual">May 14, 2019</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>Non-relapse Mortality (NRM) at Day 100</measure>
    <time_frame>Up to day 100</time_frame>
    <description>NRM is defined as death due to GVHD, infections, sepsis, organ (lung, liver, kidney) toxicity. Death from underlying disease (i.e. progression or relapse) is not considered NRM.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Non-relapse Mortality (NRM) at Day 365</measure>
    <time_frame>Up to day 365</time_frame>
    <description>NRM is defined as death due to GVHD, infections, sepsis, organ (lung, liver, kidney) toxicity. Death from underlying disease (i.e. progression or relapse) is not considered NRM.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Acute Graft Versus Host Disease (GVHD)</measure>
    <time_frame>Up to day 365</time_frame>
    <description>Cases of acute graft versus host disease (GVHD) will be diagnosed by the treating physician and will be reported as a count of participants with acute GVHD.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Chronic GVHD</measure>
    <time_frame>Up to day 365</time_frame>
    <description>Chronic GVHD will be assessed based on criteria established by the National Institutes of Health Consensus Development Project in 2005, and recently updated in 2014. This will be reported as a count of participants diagnosed with chronic GVHD</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival at One Year</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>Overall survival is defined as the number of participants remaining alive up to one year following stem cell transplant.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Free Survival at One Year</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>Disease free survival is defined as an absence of disease relapse or progression up to one year following stem cell transplant.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Different Clinical Responses</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>Clinical Responses were determined by disease-specific criteria taking into account multiple clinical and molecular markers. Multiple Myeloma (MM) response was determined using International Myeloma Working Group (IMWG) consensus criteria for response. Participants with MM had either Stringent Complete Response (sCR) or Very Good Partial Response (VGPR). Myelofibrosis (MF) response was determined using International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European LeukemiaNet (ELN) consensus criteria. Participants with MF had either Complete Response (CR) or Stable Disease (SD) (also referred to in the protocol as no response).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Minimal Residual Disease (MRD) Response</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>After bone marrow transplant, bone marrow was collected every 3-6 months (as clinically indicated per treating investigator) for up to one year after bone marrow transplant. Bone marrow was evaluated by a clinical pathologist for any evidence of multiple myeloma (MM) or myelofibrosis (MF). Evidence of MM or MF in the bone marrow is referred to as minimal residual disease (MRD). A participant with evidence of MRD is MRD-positive. A participant with no evidence of MRD is MRD-negative, which is considered an MRD response. This outcome reports the number participants with MRD responses any time between bone marrow transplant up to one year of follow-up.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Anemia</condition>
  <condition>ASXL1 Gene Mutation</condition>
  <condition>EZH2 Gene Mutation</condition>
  <condition>IDH1 Gene Mutation</condition>
  <condition>IDH2 Gene Mutation</condition>
  <condition>Plasma Cell Myeloma</condition>
  <condition>Primary Myelofibrosis</condition>
  <condition>Recurrent Plasma Cell Myeloma</condition>
  <condition>Secondary Myelofibrosis</condition>
  <condition>Thrombocytopenia</condition>
  <arm_group>
    <arm_group_label>Treatment (busulfan, fludarabine, HSCT, cyclophosphamide)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receive busulfan IV over 2 hours and fludarabine IV over 30 minutes on days -5 to -2. Participants undergo HSCT on day 0. Participants then receive cyclophosphamide IV over 60 minutes on days 3 and 4.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Busulfan</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (busulfan, fludarabine, HSCT, cyclophosphamide)</arm_group_label>
    <other_name>1, 4-Bis[methanesulfonoxy]butane</other_name>
    <other_name>BUS</other_name>
    <other_name>Bussulfam</other_name>
    <other_name>Busulfanum</other_name>
    <other_name>Busulfex</other_name>
    <other_name>Busulphan</other_name>
    <other_name>CB 2041</other_name>
    <other_name>CB-2041</other_name>
    <other_name>Glyzophrol</other_name>
    <other_name>GT 41</other_name>
    <other_name>GT-41</other_name>
    <other_name>Joacamine</other_name>
    <other_name>Methanesulfonic Acid Tetramethylene Ester</other_name>
    <other_name>Methanesulfonic acid, tetramethylene ester</other_name>
    <other_name>Mielucin</other_name>
    <other_name>Misulban</other_name>
    <other_name>Misulfan</other_name>
    <other_name>Mitosan</other_name>
    <other_name>Myeleukon</other_name>
    <other_name>Myeloleukon</other_name>
    <other_name>Myelosan</other_name>
    <other_name>Mylecytan</other_name>
    <other_name>Myleran</other_name>
    <other_name>Sulfabutin</other_name>
    <other_name>Tetramethylene Bis(methanesulfonate)</other_name>
    <other_name>Tetramethylene bis[methanesulfonate]</other_name>
    <other_name>WR-19508</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (busulfan, fludarabine, HSCT, cyclophosphamide)</arm_group_label>
    <other_name>(-)-Cyclophosphamide</other_name>
    <other_name>2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate</other_name>
    <other_name>Carloxan</other_name>
    <other_name>Ciclofosfamida</other_name>
    <other_name>Ciclofosfamide</other_name>
    <other_name>Cicloxal</other_name>
    <other_name>Clafen</other_name>
    <other_name>Claphene</other_name>
    <other_name>CP monohydrate</other_name>
    <other_name>CTX</other_name>
    <other_name>CYCLO-cell</other_name>
    <other_name>Cycloblastin</other_name>
    <other_name>Cycloblastine</other_name>
    <other_name>Cyclophospham</other_name>
    <other_name>Cyclophosphamid monohydrate</other_name>
    <other_name>Cyclophosphamidum</other_name>
    <other_name>Cyclophosphan</other_name>
    <other_name>Cyclophosphane</other_name>
    <other_name>Cyclophosphanum</other_name>
    <other_name>Cyclostin</other_name>
    <other_name>Cyclostine</other_name>
    <other_name>Cytophosphan</other_name>
    <other_name>Cytophosphane</other_name>
    <other_name>Cytoxan</other_name>
    <other_name>Fosfaseron</other_name>
    <other_name>Genoxal</other_name>
    <other_name>Genuxal</other_name>
    <other_name>Ledoxina</other_name>
    <other_name>Mitoxan</other_name>
    <other_name>Neosar</other_name>
    <other_name>Revimmune</other_name>
    <other_name>Syklofosfamid</other_name>
    <other_name>WR- 138719</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fludarabine</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (busulfan, fludarabine, HSCT, cyclophosphamide)</arm_group_label>
    <other_name>Fluradosa</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Hematopoietic Cell Transplantation</intervention_name>
    <description>Undergo HSCT</description>
    <arm_group_label>Treatment (busulfan, fludarabine, HSCT, cyclophosphamide)</arm_group_label>
    <other_name>HCT</other_name>
    <other_name>Hematopoietic Stem Cell Transplantation</other_name>
    <other_name>HSCT</other_name>
    <other_name>stem cell transplantation</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (busulfan, fludarabine, HSCT, cyclophosphamide)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1&#xD;
&#xD;
          -  Participants must have one of the following diagnoses of multiple myeloma (MM) or&#xD;
             primary/secondary myelofibrosis (MF)&#xD;
&#xD;
          -  Participants must have histologically documented multiple myeloma (MM)&#xD;
&#xD;
               -  Participants in early relapse (less than 24 months from initiation of systemic&#xD;
                  anti-myeloma therapy which may include single or planned tandem autologous&#xD;
                  transplant) after primary therapy that included and autologous HSCT; OR&#xD;
&#xD;
               -  Later stage; OR&#xD;
&#xD;
               -  High risk factors defined by the presence of any one of the following detected at&#xD;
                  any time prior to enrollment: deletion of chromosome 13 by conventional&#xD;
                  cytogenetics, hypodiploidy, abnormality in chromosome 1 (1q amplification or 1p&#xD;
                  deletion), t(4;14), t(14;16), t(14;20) or deletion of 17p by fluorescence in situ&#xD;
                  hybridization (FISH) or conventional karyotyping; high risk criteria based on&#xD;
                  commercially available gene expression profiling; OR&#xD;
&#xD;
               -  Extramedullary disease, plasma cell leukemia or high lactate dehydrogenase (LDH)&#xD;
&#xD;
          -  Participants must have histologically documented myelofibrosis (MF)&#xD;
&#xD;
               -  Participants with Dynamic International Prognostic Scoring System (DIPSS) plus&#xD;
                  intermediate stage 2 or higher risk MF; OR&#xD;
&#xD;
               -  Subset of intermediate stage 1 participants; defined by:&#xD;
&#xD;
                    -  Poor-risk molecular profile (triple negative: JAK2, CALR, MPL); OR&#xD;
&#xD;
                    -  Presence of any of the following mutations: ASXL1, SRSF2, EZH2, IDH1/2; OR&#xD;
&#xD;
                    -  Severe thrombocytopenia, severe anemia, high peripheral blood blasts&#xD;
                       percentage; OR&#xD;
&#xD;
                    -  Unfavorable cytogenetic abnormalities (rearrangements of chromosome 5 or 7&#xD;
                       or &gt;= 3 abnormalities&#xD;
&#xD;
          -  Able to provide informed consent and willing to sign an approved consent form that&#xD;
             conforms to federal and institutional guidelines&#xD;
&#xD;
          -  DONOR: A related donor - fully matched&#xD;
&#xD;
          -  DONOR: A related donor - haploidentical&#xD;
&#xD;
          -  DONOR: An unrelated donor - fully matched&#xD;
&#xD;
          -  DONOR: An unrelated donor -9/10 matched&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Cardiac-left ventricular ejection fraction &lt; 40%, symptomatic coronary artery disease,&#xD;
             or uncontrolled arrhythmias&#xD;
&#xD;
          -  Pulmonary-forced expiratory volume at one second (FEV1) or diffusion capacity of lung&#xD;
             for carbon dioxide (DLCO) &lt; 40% or history of chronic use of supplemental oxygen.&#xD;
             Temporary use of supplemental oxygen at the time of screening or registration is&#xD;
             allowed if the investigator feels that the underlying cause of requiring oxygen is&#xD;
             reversible by the time treatment begins.&#xD;
&#xD;
          -  Renal-calculated or measured glomerular filtration rate (GFR) &lt; 30 ml/min,&#xD;
             dialysis-dependent, or history of renal transplant&#xD;
&#xD;
          -  Hepatic-bilirubin &gt; 2 X upper limit of normal (ULN)&#xD;
&#xD;
          -  Alanine aminotransferase (ALT) &gt; 2.5 X ULN or cirrhosis&#xD;
&#xD;
          -  Participants with active or uncontrolled bacterial, viral, or fungal infections&#xD;
             requiring systemic therapy&#xD;
&#xD;
          -  Pregnant women, nursing mothers or women of child-bearing potential who are unwilling&#xD;
             to use medically accepted methods of contraception&#xD;
&#xD;
          -  Male and female subjects not willing to agree to medically accepted methods of&#xD;
             contraception&#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>Catherine Lee, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Huntsman Cancer Institute/ University of Utah</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Huntsman Cancer Institute/University of Utah</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>October 2, 2017</study_first_submitted>
  <study_first_submitted_qc>October 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 6, 2017</study_first_posted>
  <results_first_submitted>May 14, 2020</results_first_submitted>
  <results_first_submitted_qc>May 14, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">May 27, 2020</results_first_posted>
  <last_update_submitted>May 3, 2022</last_update_submitted>
  <last_update_submitted_qc>May 3, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 5, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Myeloma</mesh_term>
    <mesh_term>Neoplasms, Plasma Cell</mesh_term>
    <mesh_term>Thrombocytopenia</mesh_term>
    <mesh_term>Primary Myelofibrosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Busulfan</mesh_term>
    <mesh_term>Fludarabine</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 29, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/50/NCT03303950/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>All Particpants - Treatment</title>
          <description>Participants receive busulfan IV over 2 hours and fludarabine IV over 30 minutes on days -5 to -2. Participants undergo hematopoietic stem cell transplant (HSCT) on day 0. Participants then receive cyclophosphamide IV over 60 minutes on days 3 and 4.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>All Participants - Treatment</title>
          <description>Participants receive busulfan IV over 2 hours and fludarabine IV over 30 minutes on days -5 to -2. Participants undergo hematopoietic stem cell transplant (HSCT) on day 0. Participants then receive cyclophosphamide IV over 60 minutes on days 3 and 4.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="6"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="56.17" spread="6.97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="54.5" lower_limit="50" upper_limit="69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Non-relapse Mortality (NRM) at Day 100</title>
        <description>NRM is defined as death due to GVHD, infections, sepsis, organ (lung, liver, kidney) toxicity. Death from underlying disease (i.e. progression or relapse) is not considered NRM.</description>
        <time_frame>Up to day 100</time_frame>
        <group_list>
          <group group_id="O1">
            <title>All Participants - Treatment</title>
            <description>Participants receive busulfan IV over 2 hours and fludarabine IV over 30 minutes on days -5 to -2. Participants undergo hematopoietic stem cell transplant (HSCT) on day 0. Participants then receive cyclophosphamide IV over 60 minutes on days 3 and 4.</description>
          </group>
        </group_list>
        <measure>
          <title>Non-relapse Mortality (NRM) at Day 100</title>
          <description>NRM is defined as death due to GVHD, infections, sepsis, organ (lung, liver, kidney) toxicity. Death from underlying disease (i.e. progression or relapse) is not considered NRM.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Non-relapse Mortality (NRM) at Day 365</title>
        <description>NRM is defined as death due to GVHD, infections, sepsis, organ (lung, liver, kidney) toxicity. Death from underlying disease (i.e. progression or relapse) is not considered NRM.</description>
        <time_frame>Up to day 365</time_frame>
        <group_list>
          <group group_id="O1">
            <title>All Participants - Treatment</title>
            <description>Participants receive busulfan IV over 2 hours and fludarabine IV over 30 minutes on days -5 to -2. Participants undergo hematopoietic stem cell transplant (HSCT) on day 0. Participants then receive cyclophosphamide IV over 60 minutes on days 3 and 4.</description>
          </group>
        </group_list>
        <measure>
          <title>Non-relapse Mortality (NRM) at Day 365</title>
          <description>NRM is defined as death due to GVHD, infections, sepsis, organ (lung, liver, kidney) toxicity. Death from underlying disease (i.e. progression or relapse) is not considered NRM.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Acute Graft Versus Host Disease (GVHD)</title>
        <description>Cases of acute graft versus host disease (GVHD) will be diagnosed by the treating physician and will be reported as a count of participants with acute GVHD.</description>
        <time_frame>Up to day 365</time_frame>
        <group_list>
          <group group_id="O1">
            <title>All Particpants - Treatment</title>
            <description>Participants receive busulfan IV over 2 hours and fludarabine IV over 30 minutes on days -5 to -2. Participants undergo hematopoietic stem cell transplant (HSCT) on day 0. Participants then receive cyclophosphamide IV over 60 minutes on days 3 and 4.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Acute Graft Versus Host Disease (GVHD)</title>
          <description>Cases of acute graft versus host disease (GVHD) will be diagnosed by the treating physician and will be reported as a count of participants with acute GVHD.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Chronic GVHD</title>
        <description>Chronic GVHD will be assessed based on criteria established by the National Institutes of Health Consensus Development Project in 2005, and recently updated in 2014. This will be reported as a count of participants diagnosed with chronic GVHD</description>
        <time_frame>Up to day 365</time_frame>
        <group_list>
          <group group_id="O1">
            <title>All Particpants - Treatment</title>
            <description>Participants receive busulfan IV over 2 hours and fludarabine IV over 30 minutes on days -5 to -2. Participants undergo hematopoietic stem cell transplant (HSCT) on day 0. Participants then receive cyclophosphamide IV over 60 minutes on days 3 and 4.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Chronic GVHD</title>
          <description>Chronic GVHD will be assessed based on criteria established by the National Institutes of Health Consensus Development Project in 2005, and recently updated in 2014. This will be reported as a count of participants diagnosed with chronic GVHD</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival at One Year</title>
        <description>Overall survival is defined as the number of participants remaining alive up to one year following stem cell transplant.</description>
        <time_frame>Up to 1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>All Particpants - Treatment</title>
            <description>Participants receive busulfan IV over 2 hours and fludarabine IV over 30 minutes on days -5 to -2. Participants undergo hematopoietic stem cell transplant (HSCT) on day 0. Participants then receive cyclophosphamide IV over 60 minutes on days 3 and 4.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival at One Year</title>
          <description>Overall survival is defined as the number of participants remaining alive up to one year following stem cell transplant.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Disease Free Survival at One Year</title>
        <description>Disease free survival is defined as an absence of disease relapse or progression up to one year following stem cell transplant.</description>
        <time_frame>Up to 1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>All Particpants - Treatment</title>
            <description>Participants receive busulfan IV over 2 hours and fludarabine IV over 30 minutes on days -5 to -2. Participants undergo hematopoietic stem cell transplant (HSCT) on day 0. Participants then receive cyclophosphamide IV over 60 minutes on days 3 and 4.</description>
          </group>
        </group_list>
        <measure>
          <title>Disease Free Survival at One Year</title>
          <description>Disease free survival is defined as an absence of disease relapse or progression up to one year following stem cell transplant.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Different Clinical Responses</title>
        <description>Clinical Responses were determined by disease-specific criteria taking into account multiple clinical and molecular markers. Multiple Myeloma (MM) response was determined using International Myeloma Working Group (IMWG) consensus criteria for response. Participants with MM had either Stringent Complete Response (sCR) or Very Good Partial Response (VGPR). Myelofibrosis (MF) response was determined using International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European LeukemiaNet (ELN) consensus criteria. Participants with MF had either Complete Response (CR) or Stable Disease (SD) (also referred to in the protocol as no response).</description>
        <time_frame>Up to 1 year</time_frame>
        <population>one participant was not evaluable due to failure to engraft (no response assessments performed)</population>
        <group_list>
          <group group_id="O1">
            <title>All Particpants - Treatment</title>
            <description>Participants receive busulfan IV over 2 hours and fludarabine IV over 30 minutes on days -5 to -2. Participants undergo hematopoietic stem cell transplant (HSCT) on day 0. Participants then receive cyclophosphamide IV over 60 minutes on days 3 and 4.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Different Clinical Responses</title>
          <description>Clinical Responses were determined by disease-specific criteria taking into account multiple clinical and molecular markers. Multiple Myeloma (MM) response was determined using International Myeloma Working Group (IMWG) consensus criteria for response. Participants with MM had either Stringent Complete Response (sCR) or Very Good Partial Response (VGPR). Myelofibrosis (MF) response was determined using International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European LeukemiaNet (ELN) consensus criteria. Participants with MF had either Complete Response (CR) or Stable Disease (SD) (also referred to in the protocol as no response).</description>
          <population>one participant was not evaluable due to failure to engraft (no response assessments performed)</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Stringent Complete Response (sCR)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Very Good Partial Response (VGPR)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Complete Response (CR)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Stable Disease (SD)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Minimal Residual Disease (MRD) Response</title>
        <description>After bone marrow transplant, bone marrow was collected every 3-6 months (as clinically indicated per treating investigator) for up to one year after bone marrow transplant. Bone marrow was evaluated by a clinical pathologist for any evidence of multiple myeloma (MM) or myelofibrosis (MF). Evidence of MM or MF in the bone marrow is referred to as minimal residual disease (MRD). A participant with evidence of MRD is MRD-positive. A participant with no evidence of MRD is MRD-negative, which is considered an MRD response. This outcome reports the number participants with MRD responses any time between bone marrow transplant up to one year of follow-up.</description>
        <time_frame>Up to 1 year</time_frame>
        <population>one participant was not evaluable due to failure to engraft (no response assessments performed)</population>
        <group_list>
          <group group_id="O1">
            <title>All Particpants - Treatment</title>
            <description>Participants receive busulfan IV over 2 hours and fludarabine IV over 30 minutes on days -5 to -2. Participants undergo hematopoietic stem cell transplant (HSCT) on day 0. Participants then receive cyclophosphamide IV over 60 minutes on days 3 and 4.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Minimal Residual Disease (MRD) Response</title>
          <description>After bone marrow transplant, bone marrow was collected every 3-6 months (as clinically indicated per treating investigator) for up to one year after bone marrow transplant. Bone marrow was evaluated by a clinical pathologist for any evidence of multiple myeloma (MM) or myelofibrosis (MF). Evidence of MM or MF in the bone marrow is referred to as minimal residual disease (MRD). A participant with evidence of MRD is MRD-positive. A participant with no evidence of MRD is MRD-negative, which is considered an MRD response. This outcome reports the number participants with MRD responses any time between bone marrow transplant up to one year of follow-up.</description>
          <population>one participant was not evaluable due to failure to engraft (no response assessments performed)</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse Events (AEs) and Serious Adverse Events (SAEs) were collected from Day -6 (6 days prior to stem cell transplant) to day +365 (365 days after stem cell transplant), approximately one year total.</time_frame>
      <desc>The occurrence of AEs was sought by non-directive questioning of the participant at each visit or phone contact, or when they were volunteered by the participant during or between visits, or through physical examination, laboratory test, or other assessments. Only G3-4 non-hematologic toxicities related to study treatment, engraftment failure, and SAEs were recorded and reported here. Relapse of disease or chronic or acute GVHD were not treated as AEs unless leading to a fatal outcome.</desc>
      <group_list>
        <group group_id="E1">
          <title>All Participants - Treatment</title>
          <description>Participants receive busulfan IV over 2 hours and fludarabine IV over 30 minutes on days -5 to -2. Participants undergo hematopoietic stem cell transplant (HSCT) on day 0. Participants then receive cyclophosphamide IV over 60 minutes on days 3 and 4.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Blood and lymphatic system disorders - Other</sub_title>
                <description>Engraftment Failure</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Death NOS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatobiliary disorders - Other</sub_title>
                <description>Sinusoidal Obstruction Syndrome</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Sinus disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hypophosphatemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hypomagnesemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Vasovagal reaction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Data Manager</name_or_title>
      <organization>HCI Research Compliance Office</organization>
      <phone>8015850601</phone>
      <email>compliance@hci.utah.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03303950
org study id: HCI98381
nct id: NCT03303950
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This phase II trial studies how well busulfan, fludarabine, donor stem cell transplant, and
      cyclophosphamide in treating participants with multiple myeloma or myelofibrosis. Drugs used
      in chemotherapy, such as busulfan, fludarabine, and cyclophosphamide, work in different ways
      to stop the growth of cancer cells, either by killing the cells, by stopping them from
      dividing, or by stopping them from spreading. Giving chemotherapy before a donor stem cell
      transplant helps stop the growth of cells in the bone marrow, including normal blood-forming
      cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused
      into the participant they may help the participant's bone marrow make stem cells, red blood
      cells, white blood cells, and platelets. Giving busulfan and fludarabine before and
      cyclophosphamide after donor stem cell may work better in treating participants with multiple
      myeloma or myelofibrosis.
PRIMARY OBJECTIVES:

      I. To evaluate non-relapse mortality (NRM) up to day +100.

      SECONDARY OBJECTIVES:

      I. To evaluate non-relapse mortality (NRM) up to day +365. II. To evaluate the incidence of
      acute graft versus host disease (GVHD) and chronic GVHD up to day +365 post-transplant.

      III. To evaluate the overall survival and disease free survival up to 1 year. IV. To evaluate
      clinical response and molecular response (complete response and partial response) up to 1
      year.

      OUTLINE:

      Participants receive busulfan intravenously (IV) over 2 hours and fludarabine IV over 30
      minutes on days -5 to -2. Participants undergo hematopoietic cell transplantation (HSCT) on
      day 0. Participants then receive cyclophosphamide IV over 60 minutes on days 3 and 4.

      After completion of study treatment, participants are followed up for 1 year.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Non-relapse Mortality (NRM) at Day 100
time frame: Up to day 100
description: NRM is defined as death due to GVHD, infections, sepsis, organ (lung, liver, kidney) toxicity. Death from underlying disease (i.e. progression or relapse) is not considered NRM.
measure: Non-relapse Mortality (NRM) at Day 365
time frame: Up to day 365
description: NRM is defined as death due to GVHD, infections, sepsis, organ (lung, liver, kidney) toxicity. Death from underlying disease (i.e. progression or relapse) is not considered NRM.
measure: Incidence of Acute Graft Versus Host Disease (GVHD)
time frame: Up to day 365
description: Cases of acute graft versus host disease (GVHD) will be diagnosed by the treating physician and will be reported as a count of participants with acute GVHD.
measure: Incidence of Chronic GVHD
time frame: Up to day 365
description: Chronic GVHD will be assessed based on criteria established by the National Institutes of Health Consensus Development Project in 2005, and recently updated in 2014. This will be reported as a count of participants diagnosed with chronic GVHD
measure: Overall Survival at One Year
time frame: Up to 1 year
description: Overall survival is defined as the number of participants remaining alive up to one year following stem cell transplant.
measure: Disease Free Survival at One Year
time frame: Up to 1 year
description: Disease free survival is defined as an absence of disease relapse or progression up to one year following stem cell transplant.
measure: Number of Participants With Different Clinical Responses
time frame: Up to 1 year
description: Clinical Responses were determined by disease-specific criteria taking into account multiple clinical and molecular markers. Multiple Myeloma (MM) response was determined using International Myeloma Working Group (IMWG) consensus criteria for response. Participants with MM had either Stringent Complete Response (sCR) or Very Good Partial Response (VGPR). Myelofibrosis (MF) response was determined using International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European LeukemiaNet (ELN) consensus criteria. Participants with MF had either Complete Response (CR) or Stable Disease (SD) (also referred to in the protocol as no response).
measure: Number of Participants With Minimal Residual Disease (MRD) Response
time frame: Up to 1 year
description: After bone marrow transplant, bone marrow was collected every 3-6 months (as clinically indicated per treating investigator) for up to one year after bone marrow transplant. Bone marrow was evaluated by a clinical pathologist for any evidence of multiple myeloma (MM) or myelofibrosis (MF). Evidence of MM or MF in the bone marrow is referred to as minimal residual disease (MRD). A participant with evidence of MRD is MRD-positive. A participant with no evidence of MRD is MRD-negative, which is considered an MRD response. This outcome reports the number participants with MRD responses any time between bone marrow transplant up to one year of follow-up.
arm group label: Treatment (busulfan, fludarabine, HSCT, cyclophosphamide)
arm group type: Experimental
description: Participants receive busulfan IV over 2 hours and fludarabine IV over 30 minutes on days -5 to -2. Participants undergo HSCT on day 0. Participants then receive cyclophosphamide IV over 60 minutes on days 3 and 4.
intervention type: Drug
intervention name: Busulfan
description: Given IV
arm group label: Treatment (busulfan, fludarabine, HSCT, cyclophosphamide)
other name: 1, 4-Bis[methanesulfonoxy]butane
other name: BUS
other name: Bussulfam
other name: Busulfanum
other name: Busulfex
other name: Busulphan
other name: CB 2041
other name: CB-2041
other name: Glyzophrol
other name: GT 41
other name: GT-41
other name: Joacamine
other name: Methanesulfonic Acid Tetramethylene Ester
other name: Methanesulfonic acid, tetramethylene ester
other name: Mielucin
other name: Misulban
other name: Misulfan
other name: Mitosan
other name: Myeleukon
other name: Myeloleukon
other name: Myelosan
other name: Mylecytan
other name: Myleran
other name: Sulfabutin
other name: Tetramethylene Bis(methanesulfonate)
other name: Tetramethylene bis[methanesulfonate]
other name: WR-19508
intervention type: Drug
intervention name: Cyclophosphamide
description: Given IV
arm group label: Treatment (busulfan, fludarabine, HSCT, cyclophosphamide)
other name: (-)-Cyclophosphamide
other name: 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
other name: Carloxan
other name: Ciclofosfamida
other name: Ciclofosfamide
other name: Cicloxal
other name: Clafen
other name: Claphene
other name: CP monohydrate
other name: CTX
other name: CYCLO-cell
other name: Cycloblastin
other name: Cycloblastine
other name: Cyclophospham
other name: Cyclophosphamid monohydrate
other name: Cyclophosphamidum
other name: Cyclophosphan
other name: Cyclophosphane
other name: Cyclophosphanum
other name: Cyclostin
other name: Cyclostine
other name: Cytophosphan
other name: Cytophosphane
other name: Cytoxan
other name: Fosfaseron
other name: Genoxal
other name: Genuxal
other name: Ledoxina
other name: Mitoxan
other name: Neosar
other name: Revimmune
other name: Syklofosfamid
other name: WR- 138719
intervention type: Drug
intervention name: Fludarabine
description: Given IV
arm group label: Treatment (busulfan, fludarabine, HSCT, cyclophosphamide)
other name: Fluradosa
intervention type: Procedure
intervention name: Hematopoietic Cell Transplantation
description: Undergo HSCT
arm group label: Treatment (busulfan, fludarabine, HSCT, cyclophosphamide)
other name: HCT
other name: Hematopoietic Stem Cell Transplantation
other name: HSCT
other name: stem cell transplantation
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Treatment (busulfan, fludarabine, HSCT, cyclophosphamide)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Catherine Lee, MD
role: Principal Investigator
affiliation: Huntsman Cancer Institute/ University of Utah
facility: 
country: United States
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Thrombocytopenia
mesh term: Primary Myelofibrosis
mesh term: Cyclophosphamide
mesh term: Busulfan
mesh term: Fludarabine
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 