<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/NCT02994784</url>
  </required_header>
  <id_info>
    <org_study_id>H-35835</org_study_id>
    <nct_id>NCT02994784</nct_id>
  </id_info>
  <brief_title>Propylene Glycol-Free Melphalan Hydrochloride (Evomela) in AL Amyloidosis Patients</brief_title>
  <official_title>A Phase II Single-Center, Open-Label, Safety and Efficacy Study of Propylene Glycol-Free Melphalan Hydrochloride (Evomela) in AL Amyloidosis Patients Undergoing Autologous Stem Cell Transplantation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boston Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Spectrum Pharmaceuticals, Inc</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Boston Medical Center</source>
  <oversight_info>
    <has_dmc>No</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 single arm, open label study designed to evaluate the safety and efficacy of&#xD;
      propylene glycol-free melphalan hydrochloride in patients with AL amyloidosis. Treatment will&#xD;
      be comprised of propylene glycol-free melphalan hydrochloride administered intravenously at a&#xD;
      dose of 70-100 mg/m2/day on Days -3 and -2 as conditioning prior to autologous stem cell&#xD;
      transplantation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      After giving written informed consent, subjects will be evaluated for eligibility for&#xD;
      enrollment in the study. Baseline evaluations will be performed as outlined in Section 7.&#xD;
      Subjects who satisfy all inclusion and exclusion criteria will begin the study drug. Subjects&#xD;
      will be monitored from the time of the medication administration until discharge from the&#xD;
      transplant program for safety. Organ function and hematologic status will also be measured at&#xD;
      6 and 12 month follow-up visits.&#xD;
&#xD;
      Standard response criteria for AL amyloidosis hematologic and organ response will be used.&#xD;
      Overall response rate will be measured and participants will be categorized into complete&#xD;
      response, very good partial response, partial response and progressive disease. Progression&#xD;
      free survival, organ response, and safety and tolerability of propylene glycol-free melphalan&#xD;
      hydrochloride will be assessed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Slow Accrual during COVID pandemic, alternative treatments available. Study halted early.&#xD;
  </why_stopped>
  <start_date type="Actual">January 8, 2018</start_date>
  <completion_date type="Actual">July 1, 2022</completion_date>
  <primary_completion_date type="Actual">July 1, 2022</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>Number of Participants With Renal Dysfunction</measure>
    <time_frame>100 days</time_frame>
    <description>To determine the safety profile of propylene glycol-free melphalan hydrochloride in the conditioning regimen prior to autologous stem cell transplantation in AL amyloidosis patients, including adverse events related to renal dysfunction (was acute renal failure is defined as either a &gt;/=1 mg/dL increase in serum creatinine or a doubling of serum creatinine to &gt;/=1.5 mg/dL for at least 2 days.).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With Cardiac Dysfunction (New Arrhythmia)</measure>
    <time_frame>100 days</time_frame>
    <description>To determine the safety profile of propylene glycol-free melphalan hydrochloride in the conditioning regimen prior to autologous stem cell transplantation in AL amyloidosis patients, including adverse events related to cardiac dysfunction (new arrhythmia).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Neutrophil Engraftment</measure>
    <time_frame>3 weeks</time_frame>
    <description>time to neutrophil engraftment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Platelet Engraftment</measure>
    <time_frame>100 days</time_frame>
    <description>Assess time to platelet engraftment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment Related Mortality</measure>
    <time_frame>100 days</time_frame>
    <description>Number of patients who expire within 100 days of transplant</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hematologic Overall Response Rate</measure>
    <time_frame>6 months</time_frame>
    <description>Number of patients with response based on Gertz, Palladini criteria (below) Complete response (CR): Normal serum free light chain ratio,Negative serum and urine immunofixation electrophoresis Very good partial response (VGPR): Difference in serum free light chains less than 40 mg/L Partial Response (PR): &gt;50% Reduction in the difference in serum free light chains Stable Disease (SD): Meets neither criteria for CR, VGPR, PR or PD</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Organ Response</measure>
    <time_frame>12 months</time_frame>
    <description>Number of patients with organ response based on Gertz criteria (below)&#xD;
Kidney: 50% reduction in 24-hour urine protein excretion in the absence of progressive renal insufficiency (defined as a 25% increase in serum creatinine, as long as that is &gt; to an absolute increase of 0.5 mg/dL). In the case of nephrotic syndrome: a decrease in proteinuria to &lt; 1g/24h and an improvement in one of 2 extrarenal features - normalization of serum albumin or resolution of edema and/or discontinuation of diuretics in response to improvement in edema.&#xD;
Heart: ≥ 2 mm reduction in the interventricular septal (IVS) thickness by echocardiogram, improvement of ejection fraction by ≥ 20% (echocardiogram must be performed at the same institution), or decrease in 2 NYHA classes without increase in diuretic need.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Participants With Peri-transplant Hospitalizations</measure>
    <time_frame>100 days</time_frame>
    <description>Number of participants with peri-transplant hospitalizations</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">27</enrollment>
  <condition>Amyloidosis; Systemic</condition>
  <arm_group>
    <arm_group_label>Evomela</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Propylene Glycol-Free Melphalan Hydrochloride (Evomela) administered intravenously at 70-100 mg/m2/day on Days -3 and -2 prior to autologous stem cell transplantation</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Propylene Glycol-Free Melphalan Hydrochloride</intervention_name>
    <description>Intravenous Propylene Glycol-Free Melphalan Hydrochloride</description>
    <arm_group_label>Evomela</arm_group_label>
    <other_name>Evomela</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18 years or older&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group Performance Status 0-2&#xD;
&#xD;
          -  Histologic diagnosis of primary systemic (AL) amyloidosis based on:&#xD;
&#xD;
               -  Deposition of amyloid material by Congo red stain showing characteristic apple&#xD;
                  green birefringence AND&#xD;
&#xD;
               -  Evidence of a clonal plasma cell dyscrasia with monoclonal protein in the serum&#xD;
                  or urine by immunofixation electrophoresis AND/OR abnormal serum free light chain&#xD;
                  assay AND/OR clonal plasma cells in the bone marrow exam demonstrated by&#xD;
                  immunohistochemistry, flow cytometry, or in situ hybridization AND&#xD;
&#xD;
               -  Evidence of organ involvement&#xD;
&#xD;
          -  Eligible for treatment with high dose melphalan and stem cell transplantation per&#xD;
             institutional guidelines&#xD;
&#xD;
          -  Ability to understand and willingness to sign informed consent&#xD;
&#xD;
          -  Pulmonary Function Test demonstrating a diffusion capacity of lung for carbon monoxide&#xD;
             ≥ 50%&#xD;
&#xD;
          -  Left ventricular ejection fraction ≥40%&#xD;
&#xD;
          -  Systolic blood pressure &gt;90 mm Hg (supine position)&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group Performance status of 2 or better (unless patient&#xD;
             is diagnosed with AL amyloidosis involving the gastrointestinal and&#xD;
             peripheral/autonomic nervous systems, then performance status of 3 is acceptable)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous high-dose melphalan and stem cell transplant&#xD;
&#xD;
          -  Previous total cumulative dose of oral melphalan &gt; 300 mg&#xD;
&#xD;
          -  Cytotoxic chemotherapy within the previous 28 days&#xD;
&#xD;
          -  New York Heart Association ≥3&#xD;
&#xD;
          -  Decompensated or uncontrolled heart failure&#xD;
&#xD;
          -  Oxygen dependence&#xD;
&#xD;
          -  epidermal growth factor receptor &lt; 30 ml/min&#xD;
&#xD;
          -  Active infection (i.e HIV, Hepatitis B or C)&#xD;
&#xD;
          -  Pregnancy or breastfeeding&#xD;
&#xD;
          -  Exposure to another investigational drug within 3-4 weeks prior to start of study&#xD;
             treatment&#xD;
&#xD;
          -  Ongoing alcohol or drug addiction&#xD;
&#xD;
          -  Unable or unwilling to comply with the protocol&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>John M Sloan, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Attending Physician</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Boston Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02118</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Palladini G, Dispenzieri A, Gertz MA, Kumar S, Wechalekar A, Hawkins PN, Schonland S, Hegenbart U, Comenzo R, Kastritis E, Dimopoulos MA, Jaccard A, Klersy C, Merlini G. New criteria for response to treatment in immunoglobulin light chain amyloidosis based on free light chain measurement and cardiac biomarkers: impact on survival outcomes. J Clin Oncol. 2012 Dec 20;30(36):4541-9. doi: 10.1200/JCO.2011.37.7614. Epub 2012 Oct 22.</citation>
    <PMID>23091105</PMID>
  </reference>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>November 18, 2016</study_first_submitted>
  <study_first_submitted_qc>December 13, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 16, 2016</study_first_posted>
  <results_first_submitted>April 21, 2023</results_first_submitted>
  <results_first_submitted_qc>May 22, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">May 24, 2023</results_first_posted>
  <last_update_submitted>May 22, 2023</last_update_submitted>
  <last_update_submitted_qc>May 22, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 24, 2023</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>Immunoglobulin Light-chain Amyloidosis</mesh_term>
    <mesh_term>Amyloidosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Melphalan</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>There are no plans to share individual participant data.</ipd_description>
  </patient_data>
  <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>December 6, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/84/NCT02994784/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Evomela</title>
          <description>Propylene Glycol-Free Melphalan Hydrochloride (Evomela) administered intravenously at 70-100 mg/m2/day on Days -3 and -2 prior to autologous stem cell transplantation&#xD;
Propylene Glycol-Free Melphalan Hydrochloride: Intravenous Propylene Glycol-Free Melphalan Hydrochloride</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Enrolled</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="27"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="27"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>6 Months Follow-up</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="27"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="24"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>12 Month Follow-up</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="24"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="24"/>
              </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>Evomela</title>
          <description>Propylene Glycol-Free Melphalan Hydrochloride (Evomela) administered intravenously at 70-100 mg/m2/day on Days -3 and -2 prior to autologous stem cell transplantation&#xD;
Propylene Glycol-Free Melphalan Hydrochloride: Intravenous Propylene Glycol-Free Melphalan Hydrochloride</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="27"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <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="60" lower_limit="44" upper_limit="76"/>
                  </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="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                  </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="26"/>
                  </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/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Caucasian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Renal Dysfunction</title>
        <description>To determine the safety profile of propylene glycol-free melphalan hydrochloride in the conditioning regimen prior to autologous stem cell transplantation in AL amyloidosis patients, including adverse events related to renal dysfunction (was acute renal failure is defined as either a &gt;/=1 mg/dL increase in serum creatinine or a doubling of serum creatinine to &gt;/=1.5 mg/dL for at least 2 days.).</description>
        <time_frame>100 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Evomela</title>
            <description>Propylene Glycol-Free Melphalan Hydrochloride (Evomela) administered intravenously at 70-100 mg/m2/day on Days -3 and -2 prior to autologous stem cell transplantation&#xD;
Propylene Glycol-Free Melphalan Hydrochloride: Intravenous Propylene Glycol-Free Melphalan Hydrochloride</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Renal Dysfunction</title>
          <description>To determine the safety profile of propylene glycol-free melphalan hydrochloride in the conditioning regimen prior to autologous stem cell transplantation in AL amyloidosis patients, including adverse events related to renal dysfunction (was acute renal failure is defined as either a &gt;/=1 mg/dL increase in serum creatinine or a doubling of serum creatinine to &gt;/=1.5 mg/dL for at least 2 days.).</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="27"/>
              </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>Primary</type>
        <title>Number of Participants With Cardiac Dysfunction (New Arrhythmia)</title>
        <description>To determine the safety profile of propylene glycol-free melphalan hydrochloride in the conditioning regimen prior to autologous stem cell transplantation in AL amyloidosis patients, including adverse events related to cardiac dysfunction (new arrhythmia).</description>
        <time_frame>100 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Evomela</title>
            <description>Propylene Glycol-Free Melphalan Hydrochloride (Evomela) administered intravenously at 70-100 mg/m2/day on Days -3 and -2 prior to autologous stem cell transplantation&#xD;
Propylene Glycol-Free Melphalan Hydrochloride: Intravenous Propylene Glycol-Free Melphalan Hydrochloride</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Cardiac Dysfunction (New Arrhythmia)</title>
          <description>To determine the safety profile of propylene glycol-free melphalan hydrochloride in the conditioning regimen prior to autologous stem cell transplantation in AL amyloidosis patients, including adverse events related to cardiac dysfunction (new arrhythmia).</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="27"/>
              </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>
        <type>Secondary</type>
        <title>Neutrophil Engraftment</title>
        <description>time to neutrophil engraftment</description>
        <time_frame>3 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Evomela</title>
            <description>Propylene Glycol-Free Melphalan Hydrochloride (Evomela) administered intravenously at 70-100 mg/m2/day on Days -3 and -2 prior to autologous stem cell transplantation&#xD;
Propylene Glycol-Free Melphalan Hydrochloride: Intravenous Propylene Glycol-Free Melphalan Hydrochloride</description>
          </group>
        </group_list>
        <measure>
          <title>Neutrophil Engraftment</title>
          <description>time to neutrophil engraftment</description>
          <units>days</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10" lower_limit="8" upper_limit="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Platelet Engraftment</title>
        <description>Assess time to platelet engraftment</description>
        <time_frame>100 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Evomela</title>
            <description>Propylene Glycol-Free Melphalan Hydrochloride (Evomela) administered intravenously at 70-100 mg/m2/day on Days -3 and -2 prior to autologous stem cell transplantation&#xD;
Propylene Glycol-Free Melphalan Hydrochloride: Intravenous Propylene Glycol-Free Melphalan Hydrochloride</description>
          </group>
        </group_list>
        <measure>
          <title>Platelet Engraftment</title>
          <description>Assess time to platelet engraftment</description>
          <units>days</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17" lower_limit="14" upper_limit="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Treatment Related Mortality</title>
        <description>Number of patients who expire within 100 days of transplant</description>
        <time_frame>100 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Evomela</title>
            <description>Propylene Glycol-Free Melphalan Hydrochloride (Evomela) administered intravenously at 70-100 mg/m2/day on Days -3 and -2 prior to autologous stem cell transplantation&#xD;
Propylene Glycol-Free Melphalan Hydrochloride: Intravenous Propylene Glycol-Free Melphalan Hydrochloride</description>
          </group>
        </group_list>
        <measure>
          <title>Treatment Related Mortality</title>
          <description>Number of patients who expire within 100 days of 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="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Hematologic Overall Response Rate</title>
        <description>Number of patients with response based on Gertz, Palladini criteria (below) Complete response (CR): Normal serum free light chain ratio,Negative serum and urine immunofixation electrophoresis Very good partial response (VGPR): Difference in serum free light chains less than 40 mg/L Partial Response (PR): &gt;50% Reduction in the difference in serum free light chains Stable Disease (SD): Meets neither criteria for CR, VGPR, PR or PD</description>
        <time_frame>6 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Evomela</title>
            <description>Propylene Glycol-Free Melphalan Hydrochloride (Evomela) administered intravenously at 70-100 mg/m2/day on Days -3 and -2 prior to autologous stem cell transplantation&#xD;
Propylene Glycol-Free Melphalan Hydrochloride: Intravenous Propylene Glycol-Free Melphalan Hydrochloride</description>
          </group>
        </group_list>
        <measure>
          <title>Hematologic Overall Response Rate</title>
          <description>Number of patients with response based on Gertz, Palladini criteria (below) Complete response (CR): Normal serum free light chain ratio,Negative serum and urine immunofixation electrophoresis Very good partial response (VGPR): Difference in serum free light chains less than 40 mg/L Partial Response (PR): &gt;50% Reduction in the difference in serum free light chains Stable Disease (SD): Meets neither criteria for CR, VGPR, PR or PD</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="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Organ Response</title>
        <description>Number of patients with organ response based on Gertz criteria (below)&#xD;
Kidney: 50% reduction in 24-hour urine protein excretion in the absence of progressive renal insufficiency (defined as a 25% increase in serum creatinine, as long as that is &gt; to an absolute increase of 0.5 mg/dL). In the case of nephrotic syndrome: a decrease in proteinuria to &lt; 1g/24h and an improvement in one of 2 extrarenal features - normalization of serum albumin or resolution of edema and/or discontinuation of diuretics in response to improvement in edema.&#xD;
Heart: ≥ 2 mm reduction in the interventricular septal (IVS) thickness by echocardiogram, improvement of ejection fraction by ≥ 20% (echocardiogram must be performed at the same institution), or decrease in 2 NYHA classes without increase in diuretic need.</description>
        <time_frame>12 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Evomela</title>
            <description>Propylene Glycol-Free Melphalan Hydrochloride (Evomela) administered intravenously at 70-100 mg/m2/day on Days -3 and -2 prior to autologous stem cell transplantation&#xD;
Propylene Glycol-Free Melphalan Hydrochloride: Intravenous Propylene Glycol-Free Melphalan Hydrochloride</description>
          </group>
        </group_list>
        <measure>
          <title>Organ Response</title>
          <description>Number of patients with organ response based on Gertz criteria (below)&#xD;
Kidney: 50% reduction in 24-hour urine protein excretion in the absence of progressive renal insufficiency (defined as a 25% increase in serum creatinine, as long as that is &gt; to an absolute increase of 0.5 mg/dL). In the case of nephrotic syndrome: a decrease in proteinuria to &lt; 1g/24h and an improvement in one of 2 extrarenal features - normalization of serum albumin or resolution of edema and/or discontinuation of diuretics in response to improvement in edema.&#xD;
Heart: ≥ 2 mm reduction in the interventricular septal (IVS) thickness by echocardiogram, improvement of ejection fraction by ≥ 20% (echocardiogram must be performed at the same institution), or decrease in 2 NYHA classes without increase in diuretic need.</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="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Participants With Peri-transplant Hospitalizations</title>
        <description>Number of participants with peri-transplant hospitalizations</description>
        <time_frame>100 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Evomela</title>
            <description>Propylene Glycol-Free Melphalan Hydrochloride (Evomela) administered intravenously at 70-100 mg/m2/day on Days -3 and -2 prior to autologous stem cell transplantation&#xD;
Propylene Glycol-Free Melphalan Hydrochloride: Intravenous Propylene Glycol-Free Melphalan Hydrochloride</description>
          </group>
        </group_list>
        <measure>
          <title>Participants With Peri-transplant Hospitalizations</title>
          <description>Number of participants with peri-transplant hospitalizations</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="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>12 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Evomela</title>
          <description>Propylene Glycol-Free Melphalan Hydrochloride (Evomela) administered intravenously at 70-100 mg/m2/day on Days -3 and -2 prior to autologous stem cell transplantation&#xD;
Propylene Glycol-Free Melphalan Hydrochloride: Intravenous Propylene Glycol-Free Melphalan Hydrochloride</description>
        </group>
      </group_list>
      <serious_events>
        <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="0" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac arrhythmias</sub_title>
                <description>New cardiac arrhythmias</description>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Autonomic dysfunction</sub_title>
                <counts group_id="E1" events="14" subjects_affected="14" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Renal dysfunction</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <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="25" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="25" subjects_affected="25" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="20" subjects_affected="20" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="22" subjects_affected="22" subjects_at_risk="27"/>
              </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>
    <limitations_and_caveats>Study was halted early resulting in relatively small numbers of participants analyzed.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>John M Sloan, MD</name_or_title>
      <organization>Boston Medical Center and BU School of Medicine</organization>
      <phone>617-638-7519</phone>
      <email>mark.sloan@bmc.org</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/NCT02994784
org study id: H-35835
nct id: NCT02994784
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This is a single arm, open label study designed to evaluate the safety and efficacy of
      propylene glycol-free melphalan hydrochloride in patients with AL amyloidosis. Treatment will
      be comprised of propylene glycol-free melphalan hydrochloride administered intravenously at a
      dose of 70-100 mg/m2/day on Days -3 and -2 as conditioning prior to autologous stem cell
      transplantation.
After giving written informed consent, subjects will be evaluated for eligibility for
      enrollment in the study. Baseline evaluations will be performed as outlined in Section 7.
      Subjects who satisfy all inclusion and exclusion criteria will begin the study drug. Subjects
      will be monitored from the time of the medication administration until discharge from the
      transplant program for safety. Organ function and hematologic status will also be measured at
      6 and 12 month follow-up visits.

      Standard response criteria for AL amyloidosis hematologic and organ response will be used.
      Overall response rate will be measured and participants will be categorized into complete
      response, very good partial response, partial response and progressive disease. Progression
      free survival, organ response, and safety and tolerability of propylene glycol-free melphalan
      hydrochloride will be assessed.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With Renal Dysfunction
time frame: 100 days
description: To determine the safety profile of propylene glycol-free melphalan hydrochloride in the conditioning regimen prior to autologous stem cell transplantation in AL amyloidosis patients, including adverse events related to renal dysfunction (was acute renal failure is defined as either a >/=1 mg/dL increase in serum creatinine or a doubling of serum creatinine to >/=1.5 mg/dL for at least 2 days.).
measure: Number of Participants With Cardiac Dysfunction (New Arrhythmia)
time frame: 100 days
description: To determine the safety profile of propylene glycol-free melphalan hydrochloride in the conditioning regimen prior to autologous stem cell transplantation in AL amyloidosis patients, including adverse events related to cardiac dysfunction (new arrhythmia).
measure: Neutrophil Engraftment
time frame: 3 weeks
description: time to neutrophil engraftment
measure: Platelet Engraftment
time frame: 100 days
description: Assess time to platelet engraftment
measure: Treatment Related Mortality
time frame: 100 days
description: Number of patients who expire within 100 days of transplant
measure: Hematologic Overall Response Rate
time frame: 6 months
description: Number of patients with response based on Gertz, Palladini criteria (below) Complete response (CR): Normal serum free light chain ratio,Negative serum and urine immunofixation electrophoresis Very good partial response (VGPR): Difference in serum free light chains less than 40 mg/L Partial Response (PR): >50% Reduction in the difference in serum free light chains Stable Disease (SD): Meets neither criteria for CR, VGPR, PR or PD
measure: Organ Response
time frame: 12 months
description: Number of patients with organ response based on Gertz criteria (below)
Kidney: 50% reduction in 24-hour urine protein excretion in the absence of progressive renal insufficiency (defined as a 25% increase in serum creatinine, as long as that is > to an absolute increase of 0.5 mg/dL). In the case of nephrotic syndrome: a decrease in proteinuria to < 1g/24h and an improvement in one of 2 extrarenal features - normalization of serum albumin or resolution of edema and/or discontinuation of diuretics in response to improvement in edema.
Heart: ≥ 2 mm reduction in the interventricular septal (IVS) thickness by echocardiogram, improvement of ejection fraction by ≥ 20% (echocardiogram must be performed at the same institution), or decrease in 2 NYHA classes without increase in diuretic need.
measure: Participants With Peri-transplant Hospitalizations
time frame: 100 days
description: Number of participants with peri-transplant hospitalizations
arm group label: Evomela
arm group type: Experimental
description: Propylene Glycol-Free Melphalan Hydrochloride (Evomela) administered intravenously at 70-100 mg/m2/day on Days -3 and -2 prior to autologous stem cell transplantation
intervention type: Drug
intervention name: Propylene Glycol-Free Melphalan Hydrochloride
description: Intravenous Propylene Glycol-Free Melphalan Hydrochloride
arm group label: Evomela
other name: Evomela
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: John M Sloan, MD
role: Principal Investigator
affiliation: Attending Physician
facility: 
country: United States
citation: Palladini G, Dispenzieri A, Gertz MA, Kumar S, Wechalekar A, Hawkins PN, Schonland S, Hegenbart U, Comenzo R, Kastritis E, Dimopoulos MA, Jaccard A, Klersy C, Merlini G. New criteria for response to treatment in immunoglobulin light chain amyloidosis based on free light chain measurement and cardiac biomarkers: impact on survival outcomes. J Clin Oncol. 2012 Dec 20;30(36):4541-9. doi: 10.1200/JCO.2011.37.7614. Epub 2012 Oct 22.
PMID: 23091105
responsible party type: Sponsor
mesh term: Immunoglobulin Light-chain Amyloidosis
mesh term: Amyloidosis
mesh term: Melphalan
sharing ipd: No
ipd description: There are no plans to share individual participant data.
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Study was halted early resulting in relatively small numbers of participants analyzed.
point of contact: 