<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/NCT04412707</url>
  </required_header>
  <id_info>
    <org_study_id>OP-109</org_study_id>
    <nct_id>NCT04412707</nct_id>
  </id_info>
  <brief_title>A PK, Safety and Tolerability Study of Peripheral and Central Infusion of Melflufen in RRMM Patients</brief_title>
  <acronym>PORT</acronym>
  <official_title>A Randomized, Two-period, Cross-over, Phase 2 Study, Comparing Pharmacokinetics, and Assessing Safety and Tolerability of Peripheral and Central i.v. Administration of Melphalan Flufenamide (Melflufen) in RRMM Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Oncopeptides AB</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Oncopeptides AB</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a randomized, two-period, cross-over Phase 2 study, comparing PK, and assessing&#xD;
      safety and tolerability and efficacy of peripheral and central intravenous administration of&#xD;
      melflufen in patients with RRMM. It is an international study, enrolling patients in US and&#xD;
      Europe. The study will enroll patients following at least 2 lines of prior therapy.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    The sponsor decided to terminate the study following an FDA request of a partial clinical hold.&#xD;
  </why_stopped>
  <start_date type="Actual">August 4, 2020</start_date>
  <completion_date type="Actual">January 10, 2022</completion_date>
  <primary_completion_date type="Actual">June 2, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Peak Plasma Concentration for Melphalan</measure>
    <time_frame>Cycle 1 Day 1 and Cycle 2 Day 1. Samples were collected 5, 10, 15, 20, and 25 minutes after the start of the infusion; immediately before the end of the infusion; and 5, 10, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.</time_frame>
    <description>To evaluate and compare the pharmacokinetic (PK) variable Cmax of melphalan after central and peripheral intravenous infusion of melflufen.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration Versus Time Curve AUC(0-t) of Melphalan</measure>
    <time_frame>Cycle 1 Day 1 and Cycle 2 Day 1. Samples were collected 5, 10, 15, 20, and 25 minutes after the start of the infusion; immediately before the end of the infusion; and 5, 10, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.</time_frame>
    <description>To evaluate and compare the pharmacokinetic (PK) variable AUC(0-t) of melphalan after central and peripheral intravenous infusion of melflufen.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration Versus Time Curve AUC(0-inf) of Melphalan</measure>
    <time_frame>Cycle 1 Day 1 and Cycle 2 Day 1. Samples were collected 5, 10, 15, 20, and 25 minutes after the start of the infusion; immediately before the end of the infusion; and 5, 10, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.</time_frame>
    <description>To evaluate and compare the pharmacokinetic (PK) variable AUC(0-inf) of melphalan after central and peripheral intravenous infusion of melflufen</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With Local Reactions Including Phlebitis at Infusion Site After Peripheral Intravenous Administration</measure>
    <time_frame>15 minutes and 4 hours after peripheral intravenous administration, pre- and post-infusion on Day 1 and Day 8</time_frame>
    <description>Assessment of the local tolerability of peripheral intravenous administration of melflufen using the Visual Infusion Phlebitis (VIP) scale. The VIP scale provides a score from 0 to 5, noting an ascending order of severity of inflammation. A score of 0 is the lowest possible score, meaning no inflammation detected, and 5 is the highest score, indicating the most severe reaction.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Peak Plasma Concentration for Melflufen and Desethyl-melflufen</measure>
    <time_frame>Cycle 1 Day 1 and Cycle 2 Day 1 - 13 PK samples during and post infusion (28 days cycle)</time_frame>
    <description>To evaluate and compare the pharmacokinetic (PK) variable Cmax of melflufen and desethyl-melflufen after central and peripheral intravenous infusion of melflufen.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Plasma Concentration Versus Time Curve AUC(0-t) of Melflufen and Desethyl-melflufen</measure>
    <time_frame>Cycle 1 Day 1 and Cycle 2 Day 1 - 13 PK samples during and post infusion (28 days cycle)</time_frame>
    <description>To evaluate and compare the pharmacokinetic (PK) variable AUC(0-t) of melflufen and desethyl-melflufen after central and peripheral intravenous infusion of melflufen</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Plasma Concentration Versus Time Curve AUC(0-inf) of Melflufen and Desethyl-melflufen</measure>
    <time_frame>Cycle 1 Day 1 and Cycle 2 Day 1 - 13 PK samples during and post infusion (28 days cycle)</time_frame>
    <description>To evaluate and compare the pharmacokinetic (PK) variable AUC(0-inf) of melflufen and desethyl-melflufen after central and peripheral intravenous infusion of melflufen</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Elimination Half-life (t1/2) of Melflufen, Melphalan and Desethyl-melflufen</measure>
    <time_frame>Cycle 1 Day 1 and Cycle 2 Day 1 - 13 measurements during and post infusion (28 days cycle)</time_frame>
    <description>To evaluate elimination half-life (t½) for melflufen, melphalan and desethyl-melflufen after central and peripheral intravenous infusion of melflufen.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of Treatment-Emergent Adverse Events (TEAEs) by MedDRA SOC and PT</measure>
    <time_frame>Median treatment durations for Arm A and Arm B were 29.14 weeks and 12.14 weeks, respectively. The AE reporting period is estimated to be 30 days longer.</time_frame>
    <description>To assess safety and general tolerability of melflufen by collecting non-serious Adverse Events (AEs) from the start of study treatment until 30 days after the last dose of any study drug (melflufen or dexamethasone) or initiation of subsequent therapy whichever occurred first. Serious AEs (SAEs) were collected from the time the subject signed the ICF until 30 days after the last dose of any study drug (melflufen or dexamethasone) or initiation of subsequent therapy whichever occurred first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Best Response (Stringent Complete Response (sCR), Complete Response (CR), Very Good Partial Response (VGPR), Partial Response (PR), Minimal Response (MR), Stable Disease (SD) or Progressive Disease (PD)</measure>
    <time_frame>From initiation of therapy until disease progression. Median treatment durations for Arm A and Arm B were 29.14 weeks and 12.14 weeks, respectively.</time_frame>
    <description>To assess best response during the study with the criteria established by the International Myeloma Working Group Uniform Response Criteria (IMWG-URC) for sCR, CR, VGPR, PR, SD and PD</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ORR</measure>
    <time_frame>From initiation of therapy until disease progression. Maximum treatment durations for Arm A and Arm B were 68.4 and 59.0 weeks, respectively.</time_frame>
    <description>To assess overall response rate (ORR), including CR/sCR, VGPR and PR, during the study with the criteria established by the IMWG-URC.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CBR</measure>
    <time_frame>To be assessed at the end of study drug treatment. Maximum treatment durations for Arm A and Arm B were 68.4 and 59.0 weeks, respectively.</time_frame>
    <description>To assess clinical benefit rate (CBR), i.e., proportion of patients that achieve a confirmed minimal response or better (sCR, CR, VGPR, PR and MR), during the study with the criteria established by the IMWG-URC.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DOR</measure>
    <time_frame>From confirmed response until disease progression. Maximum treatment durations for Arm A and Arm B were 68.4 and 59.0 weeks, respectively.</time_frame>
    <description>To assess duration of response (DOR): the time in months from the first evidence of confirmed assessment of sCR, CR, VGPR, or PR to first confirmed disease progression according to the criteria established by the IMWG-URC or to death due to any cause. DOR is defined only for patients with a confirmed PR or better.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DOCB</measure>
    <time_frame>From first evidence of confirmed assessment of sCR, CR, VGPR, PR or MR to first confirmed disease progression, or to death due to any cause. Maximum treatment durations for Arm A and Arm B were 68.4 and 59.0 weeks, respectively.</time_frame>
    <description>To assess duration of clinical benefit (DOCB) in patients with stringent complete response (sCR), complete response (CR), very good partial response (VGPR), PR, or MR during the study with the criteria established by the IMWG-URC.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TTR</measure>
    <time_frame>From initiation of therapy until documented disease response. Maximum treatment durations for Arm A and Arm B were 68.4 and 59.0 weeks, respectively.</time_frame>
    <description>To assess time to response (TTR) in patients with PR or better during the study with the criteria established by the UMWG-URC.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TTP</measure>
    <time_frame>From date of randomization until documented disease progression. Maximum treatment durations for Arm A and Arm B were 68.4 and 59.0 weeks, respectively.</time_frame>
    <description>To assess time to progression (TTP) during the study with the criteria established by the IMWG-URC.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TTNT</measure>
    <time_frame>From randomization to the date of next anti-myeloma treatment. Maximum treatment durations for Arm A and Arm B were 68.4 and 59.0 weeks, respectively.</time_frame>
    <description>To assess time to next treatment (TTNT)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PFS</measure>
    <time_frame>From initiation of therapy until documented disease progression or initiation of new therapy. Maximum treatment durations for Arm A and Arm B were 68.4 and 59.0 weeks, respectively.</time_frame>
    <description>To assess progression free survival (PFS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Grade 3/4 Treatment-Emergent Adverse Events (TEAEs)</measure>
    <time_frame>Median treatment durations for Arm A and Arm B were 29.14 and 12.14 weeks, respectively. The AE reporting period is estimated to be 30 days longer.</time_frame>
    <description>To assess safety and general tolerability of melflufen by collecting non-serious Adverse Events (AEs) from the start of study treatment until 30 days after the last dose of any study drug (melflufen or dexamethasone) or initiation of subsequent therapy whichever occurred first. Serious AEs (SAEs) were collected from the time the subject signed the ICF until 30 days after the last dose of any study drug (melflufen or dexamethasone) or initiation of subsequent therapy whichever occurred first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Grade 5 Treatment-Emergent Adverse Events (TEAEs)</measure>
    <time_frame>From signing of the ICF until 30 days after the last dose of any study drug or initiation of subsequent therapy, whichever comes first. Median treatment durations for Arms A and B were 29.14 weeks and 12.14 weeks. AE reporting period=30 days longer</time_frame>
    <description>To assess safety and general tolerability of melflufen by collecting serious adverse events (SAEs) from the signing of the ICF until 30 days after the last dose of any study drug (melflufen or dexamethasone) or initiation of subsequent therapy whichever comes first.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">27</enrollment>
  <condition>RRMM</condition>
  <arm_group>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Melflufen 40 mg iv Day 1 of each 28 day cycle. Dexamethasone 40 mg po Day 1,8, 15 and 22 of each 28 day cycle, if &gt; 75 years of age 20 mg. Cycle 1 will be administered via a Peripheral Venous Catheter (PVC) and cycle 2 and onwards melflufen will be administered via a Central Venous Catheter (CVC).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Melflufen 40 mg iv Day 1 of each 28 day cycle. Dexamethasone 40 mg po Day 1,8, 15 and 22 of each 28 day cycle, if &gt; 75 years of age 20 mg. Cycle 1 will be administered via a Central Venous Catheter (CVC) and cycle 2 will be administered via a Peripheral Venous Catheter (PVC). From cycle 3 and onwards melflufen will be administered via CVC.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Melphalan</intervention_name>
    <description>Peripheral versus central administration</description>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_label>Arm B</arm_group_label>
    <other_name>melflufen flufenamide</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexamethasone</intervention_name>
    <description>Oral tablets</description>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_label>Arm B</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female, age 18 years or older&#xD;
&#xD;
          2. Capable of giving signed informed consent as described in Appendix 1 which includes&#xD;
             compliance with the requirements and restrictions listed in the informed consent form&#xD;
             (ICF) and in this protocol;&#xD;
&#xD;
          3. A prior diagnosis of multiple myeloma (MM) with documented disease progression in need&#xD;
             of treatment at time of screening;&#xD;
&#xD;
          4. Measurable disease defined as any of the following:&#xD;
&#xD;
               -  Serum monoclonal protein ≥ 0.5 g/dL by serum protein electrophoresis (SPEP)&#xD;
&#xD;
               -  ≥ 200 mg/24hr of monoclonal protein in the 24hour urine collection by&#xD;
                  electrophoresis (UPEP)&#xD;
&#xD;
               -  Serum free light chain (SFLC) ≥ 10 mg/dL AND abnormal serum kappa to lambda free&#xD;
                  light chain (FLC) ratio&#xD;
&#xD;
          5. Received at least 2 prior lines of therapy and is refractory to an immunomodulatory&#xD;
             drug (IMiD) and a proteasome inhibitor (PI). The definition of refractory includes&#xD;
             intolerance to an IMiD/PI after at least two 28-day cycles of therapy, see Appendix 10&#xD;
             and Appendix 8.&#xD;
&#xD;
          6. Adequate peripheral arm veins for repeated intravenous infusions&#xD;
&#xD;
          7. Life expectancy of ≥ 6 months;&#xD;
&#xD;
          8. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2, see Appendix 6.&#xD;
             Patients with ECOG performance status &gt; 2 solely based on bone pain secondary to MM&#xD;
             may be eligible following consultation and approval of medical monitor;&#xD;
&#xD;
          9. 12-lead Electrocardiogram (ECG) with QT interval calculated by Fridericia Formula&#xD;
             (QTcF) interval of ≤ 470 msec, see Appendix 11;&#xD;
&#xD;
         10. Adequate organ function with the following laboratory results during screening (within&#xD;
             21 days) and immediately before study treatment administration on Cycle 1 Day 1:&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) ≥ 1,000 cells/mm³ (1.0 x 10⁹/L) (Growth factors&#xD;
                  cannot be used within 10 days (14 days for pegfilgrastim) prior to initiation of&#xD;
                  study treatment)&#xD;
&#xD;
               -  Platelet count ≥ 75,000 cells/ mm³ (75 x 10⁹/L) (without transfusions during the&#xD;
                  10 days prior to initiation of therapy)&#xD;
&#xD;
               -  Hemoglobin ≥ 8.0 g/dL (Red blood cell [RBC] transfusions are permitted)&#xD;
&#xD;
               -  Total Bilirubin ≤ 1.5 x upper limit of normal (ULN), except patients diagnosed&#xD;
                  with Gilbert's syndrome that have been reviewed and approved by the Medical&#xD;
                  Monitor&#xD;
&#xD;
               -  Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT)&#xD;
                  and alanine aminotransferase (ALT) serum glutamic-pyruvic transaminase (SGPT) ≤&#xD;
                  3.0 x ULN&#xD;
&#xD;
               -  Renal function: Estimated glomerular filtration rate (eGFR) by Chronic Kidney&#xD;
                  Disease Epidemiology Collaboration (CKD-EPI) formula of ≥ 45 mL/min, see Appendix&#xD;
                  12.&#xD;
&#xD;
         11. Must have or be willing to have an acceptable central catheter (Port a Cath,&#xD;
             peripherally inserted central catheter [PICC] line, or central venous catheter [CVC])&#xD;
             and a PVC;&#xD;
&#xD;
         12. a) Male patients: A male patient is eligible if he agrees to use contraception as&#xD;
             detailed in Appendix 4 of this protocol during the treatment period and for at least 3&#xD;
             months after the last dose of study treatment and refrains from donating sperm during&#xD;
             this period b) Female patients: A female patient is eligible to participate if she is&#xD;
             not pregnant, not breastfeeding, and at least one of the following conditions applies:&#xD;
             I. Not a woman of childbearing potential (WOCBP) as defined in Appendix 4 or II. A&#xD;
             WOCBP who agrees to follow the contraceptive guidance in Appendix 4 during the&#xD;
             treatment period and for at least 28 days after the last dose of study treatment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Primary refractory disease (i.e. never responded with at least minimal response [MR]&#xD;
             to any prior therapy);&#xD;
&#xD;
          2. Evidence of mucosal and/or internal bleeding or platelet transfusion refractory&#xD;
             (platelet count fails to increase by &gt; 10,000 cells/mm³ after a transfusion of an&#xD;
             appropriate dose of platelets);&#xD;
&#xD;
          3. Any medical conditions that, in the Investigator's opinion, would impose excessive&#xD;
             risk to the patient or would adversely affect his/her participating in this study.&#xD;
             Examples of such conditions are: a significant history of cardiovascular disease&#xD;
             (e.g., myocardial infarction, significant cardiac conduction system abnormalities,&#xD;
             uncontrolled hypertension, ≥ Grade 3 thromboembolic event in the last 6 months);&#xD;
&#xD;
          4. Known active infection that is uncontrolled or has required intravenous systemic&#xD;
             therapy within 14 days of randomization. Patients that have required oral&#xD;
             anti-infective treatment within 14 days of randomization should be discussed with the&#xD;
             Medical Monitor;&#xD;
&#xD;
          5. Other malignancy diagnosed or requiring treatment within the past 3 years with the&#xD;
             exception of adequately treated basal cell carcinoma, squamous cell skin cancer,&#xD;
             carcinoma in-situ of the cervix or breast or very low and low risk prostate cancer in&#xD;
             active surveillance;&#xD;
&#xD;
          6. Pregnant or breast-feeding females;&#xD;
&#xD;
          7. Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or&#xD;
             confuse compliance or follow-up evaluation;&#xD;
&#xD;
          8. Human immunodeficiency virus (HIV) or active hepatitis B or C viral infection;&#xD;
&#xD;
          9. Concurrent known or suspected amyloidosis or plasma cell leukemia;&#xD;
&#xD;
         10. POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly,&#xD;
             endocrinopathy, monoclonal protein and skin changes);&#xD;
&#xD;
         11. Known central nervous system (CNS) or meningeal involvement of myeloma&#xD;
&#xD;
         12. Any of the following treatments, within the specified timeframe&#xD;
&#xD;
               -  Previous cytotoxic therapies, including cytotoxic investigational agents, for MM&#xD;
                  within 3 weeks (6 weeks for nitrosoureas) prior to initiation of therapy.&#xD;
&#xD;
               -  The use of live vaccines within 30 days before initiation of therapy.&#xD;
&#xD;
               -  IMiDs, PIs and or corticosteroids within 2 weeks prior to initiation of therapy.&#xD;
&#xD;
               -  Other investigational therapies and monoclonal antibodies within 4 weeks of&#xD;
                  initiation of therapy.&#xD;
&#xD;
               -  Prednisone up to but no more than 10 mg orally q.d. or its equivalent for symptom&#xD;
                  management of comorbid conditions is permitted but dose should be stable for at&#xD;
                  least 7 days prior to initiation of therapy.&#xD;
&#xD;
             Other washout times may be considered following consultation with the medical monitor.&#xD;
&#xD;
         13. Residual side effects to previous therapy &gt; Grade 1 prior to initiation of therapy&#xD;
             (Alopecia any grade and/or neuropathy Grade 1 without pain are permitted);&#xD;
&#xD;
         14. Prior stem cell transplant (autologous and/or allogenic) within 6 months of initiation&#xD;
             of therapy;&#xD;
&#xD;
         15. Prior allogeneic stem cell transplantation with active graft-versus-host-disease;&#xD;
&#xD;
         16. Prior major surgical procedure or radiation therapy within 4 weeks of the initiation&#xD;
             of therapy (this does not include limited course of radiation used for management of&#xD;
             bone pain within 7 days of initiation of therapy);&#xD;
&#xD;
         17. Known intolerance to the required dose and schedule of steroid therapy, as determined&#xD;
             by the investigator;&#xD;
&#xD;
         18. Known hypersensitivity reaction to melphalan, melflufen or its excipients&#xD;
&#xD;
         19. Prior treatment with melflufen&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>The Oncology Institute of Hope &amp; Innovation - Glendale</name>
      <address>
        <city>Glendale</city>
        <state>California</state>
        <zip>91204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Specialized Hospital for Active Treatment of Hematological Diseases, Sofia</name>
      <address>
        <city>Sofia</city>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Multiprofile Hospital for Active Treatment &quot;Sveta Marina&quot;, Varna</name>
      <address>
        <city>Varna</city>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Brno, Clinic of Internal Medicine - Hematology and Oncology</name>
      <address>
        <city>Brno</city>
        <zip>62500</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Olomouc, Clinic of Hemato-Oncology</name>
      <address>
        <city>Olomouc</city>
        <zip>77900</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Central Hospital of Southern Pest National Institute of Hematology and Infectious Diseases, Department of Hematology and Stem Cell Transplantation</name>
      <address>
        <city>Budapest</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Semmelweis University, 3rd Department of Internal Medicine</name>
      <address>
        <city>Budapest</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Public Non-Profit Enterprise &quot;City Clinical Hospital #4&quot; under Dnipro City Council, Regional Hematology Center</name>
      <address>
        <city>Dnipro</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Public Non-Profit Enterprise &quot;Kyiv City Clinical Hospital #9&quot; under the Executive Body of Kyiv City Council, Hematology Department #1</name>
      <address>
        <city>Kyiv</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institute of Blood Pathology and Transfusion Medicine, Department of Hematology with Laboratory Group</name>
      <address>
        <city>Lviv</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Bulgaria</country>
    <country>Czechia</country>
    <country>Hungary</country>
    <country>Ukraine</country>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>May 18, 2020</study_first_submitted>
  <study_first_submitted_qc>May 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 2, 2020</study_first_posted>
  <results_first_submitted>May 30, 2022</results_first_submitted>
  <results_first_submitted_qc>July 18, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">August 16, 2022</results_first_posted>
  <last_update_submitted>February 9, 2023</last_update_submitted>
  <last_update_submitted_qc>February 9, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 9, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>central intravenous administration</keyword>
  <keyword>peripheral intravenous administration</keyword>
  <keyword>central venous catheter (CVC)</keyword>
  <keyword>peripheral venous catheter (PVC)</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dexamethasone</mesh_term>
    <mesh_term>Melphalan</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>March 10, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/07/NCT04412707/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 24, 2022</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/07/NCT04412707/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Arm A</title>
          <description>Melflufen 40 mg iv Day 1 of each 28-day cycle. Dexamethasone 40 mg po Days 1,8,15 and 22 of each 28-day cycle (20 mg for patients 75 years or older). Cycle 1 administered via a PVC and Cycle 2 and onwards melflufen administered via a CVC.&#xD;
Melflufen: Peripheral versus central administration&#xD;
Dexamethasone: Oral tablets</description>
        </group>
        <group group_id="P2">
          <title>Arm B</title>
          <description>Melflufen 40 mg iv Day 1 of each 28-day cycle. Dexamethasone 40 mg po Days 1,8,15 and 22 of each 28-day cycle (20 mg for patients 75 years or older). Cycle 1 administered via a CVC and Cycle 2 administered via a PVC. From Cycle 3 and onwards melflufen administered via CVC.&#xD;
Melflufen: Peripheral versus central administration&#xD;
Dexamethasone: Oral tablets</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Cycle 1</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Discontinued</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Disease progression</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Cycle 2</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Discontinued</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Disease progression</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Cycle 3 to End of Study (EOS)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Ongoing in Study at Data Cut</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Discontinued Study in Cycle 3 or Later</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Disease progression</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Study terminated by Sponsor</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Full Analysis Set</population>
      <group_list>
        <group group_id="B1">
          <title>Arm A</title>
          <description>Melflufen 40 mg iv Day 1 of each 28-day cycle. Dexamethasone 40 mg po Days 1,8,15 and 22 of each 28-day cycle (20 mg for patients 75 years or older). Cycle 1 administered via a PVC and Cycle 2 and onwards melflufen administered via a CVC.&#xD;
Melflufen: Peripheral versus central administration&#xD;
Dexamethasone: Oral tablets</description>
        </group>
        <group group_id="B2">
          <title>Arm B</title>
          <description>Melflufen 40 mg iv Day 1 of each 28-day cycle. Dexamethasone 40 mg po Days 1,8,15 and 22 of each 28-day cycle (20 mg for patients 75 years or older). Cycle 1 administered via a CVC and Cycle 2 administered via a PVC. From Cycle 3 and onwards melflufen administered via CVC.&#xD;
Melflufen: Peripheral versus central administration&#xD;
Dexamethasone: Oral tablets</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="14"/>
            <count group_id="B2" value="13"/>
            <count group_id="B3" value="27"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Age group</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="14"/>
                    <count group_id="B2" value="13"/>
                    <count group_id="B3" value="27"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>&lt;65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 - 75 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt; 75 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="5"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="14"/>
                    <count group_id="B2" value="13"/>
                    <count group_id="B3" value="27"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="13"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="14"/>
                    <count group_id="B2" value="13"/>
                    <count group_id="B3" value="27"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="26"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="14"/>
                    <count group_id="B2" value="13"/>
                    <count group_id="B3" value="27"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="27"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Hungary</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="14"/>
                    <count group_id="B2" value="13"/>
                    <count group_id="B3" value="27"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Czechia</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="14"/>
                    <count group_id="B2" value="13"/>
                    <count group_id="B3" value="27"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ukraine</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="14"/>
                    <count group_id="B2" value="13"/>
                    <count group_id="B3" value="27"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Bulgaria</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="14"/>
                    <count group_id="B2" value="13"/>
                    <count group_id="B3" value="27"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Baseline fertility status</title>
          <description>Baseline fertility status for female participants.</description>
          <population>Percentages are based on the number of female participants only.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="7"/>
                    <count group_id="B2" value="7"/>
                    <count group_id="B3" value="14"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Potentially able to bear children</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not able to bear children</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Peak Plasma Concentration for Melphalan</title>
        <description>To evaluate and compare the pharmacokinetic (PK) variable Cmax of melphalan after central and peripheral intravenous infusion of melflufen.</description>
        <time_frame>Cycle 1 Day 1 and Cycle 2 Day 1. Samples were collected 5, 10, 15, 20, and 25 minutes after the start of the infusion; immediately before the end of the infusion; and 5, 10, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.</time_frame>
        <population>Pharmacokinetic (PK) Set: All patients that received at least two melflufen doses of 40 mg and had sufficient PK samples taken at Cycle 1 and 2 for determination of all PK variables. One PK sampling series following peripheral administration and one PK sampling series following central administration. Patients with a dose reduction in cycle 2 were not evaluable for PK.</population>
        <group_list>
          <group group_id="O1">
            <title>Peripheral Venous Catheter (PVC)</title>
            <description>Combined treatment ARM for all PVC administration from both ARM A &amp; ARM B during Cycle 1 and 2. Melflufen 40 mg iv Day 1 of each 28-day cycle. Dexamethasone 40 mg po Days 1,8,15 and 22 of each 28-day cycle (20 mg for patients 75 years or older). ARM A Cycle 1 administered via a PVC and Cycle 2 and onwards melflufen administered via a CVC. ARM B Cycle 1 administered via a CVC and Cycle 2 administered via a PVC. From Cycle 3 and onwards melflufen administered via CVC. Melflufen: Peripheral versus central administration. Dexamethasone: Oral tablets.</description>
          </group>
          <group group_id="O2">
            <title>Central Venous Catheter (CVC)</title>
            <description>Combined treatment ARM for all CVC administration from both ARM A &amp; ARM B during Cycle 1 and 2. Melflufen 40 mg iv Day 1 of each 28-day cycle. Dexamethasone 40 mg po Days 1,8,15 and 22 of each 28-day cycle (20 mg for patients 75 years or older). ARM A Cycle 1 administered via a PVC and Cycle 2 and onwards melflufen administered via a CVC. ARM B Cycle 1 administered via a CVC and Cycle 2 administered via a PVC. From Cycle 3 and onwards melflufen administered via CVC. Melflufen: Peripheral versus central administration. Dexamethasone: Oral tablets.</description>
          </group>
        </group_list>
        <measure>
          <title>Peak Plasma Concentration for Melphalan</title>
          <description>To evaluate and compare the pharmacokinetic (PK) variable Cmax of melphalan after central and peripheral intravenous infusion of melflufen.</description>
          <population>Pharmacokinetic (PK) Set: All patients that received at least two melflufen doses of 40 mg and had sufficient PK samples taken at Cycle 1 and 2 for determination of all PK variables. One PK sampling series following peripheral administration and one PK sampling series following central administration. Patients with a dose reduction in cycle 2 were not evaluable for PK.</population>
          <units>ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                    <count group_id="O2" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="486.1" spread="21.34"/>
                    <measurement group_id="O2" value="530.1" spread="25.23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="546.3" spread="31.83"/>
                    <measurement group_id="O2" value="449.2" spread="40.66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Based on a geometric mean ratio (GMR) peripheral vs. central of 0.95, a 90% confidence interval (CI) for the ratio of geometric means within bioequivalence limits of 0.8 and 1.25, and 80% power, a sample size of 20 patients (10 per sequence) was required assuming a within-patient variability for period differences (in log scale) of 0.29. Approximately 25 patients were to be enrolled to achieve 20 PK- and local tolerance-evaluable patients.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>The condition for similarity was if the 90% CI for the GMR was within the bioequivalence limits of 0.8 and 1.25.</non_inferiority_desc>
            <param_type>Adjusted geometric mean ratio (GMR)</param_type>
            <param_value>0.946</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.849</ci_lower_limit>
            <ci_upper_limit>1.053</ci_upper_limit>
            <estimate_desc>CVC vs. PVC, where CVC is numerator and PVC is denominator. Linear Mixed Effect Model included terms for period, sequence and administration route (PVC or CVC) as fixed effects and subject nested within sequence as a random effect.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Plasma Concentration Versus Time Curve AUC(0-t) of Melphalan</title>
        <description>To evaluate and compare the pharmacokinetic (PK) variable AUC(0-t) of melphalan after central and peripheral intravenous infusion of melflufen.</description>
        <time_frame>Cycle 1 Day 1 and Cycle 2 Day 1. Samples were collected 5, 10, 15, 20, and 25 minutes after the start of the infusion; immediately before the end of the infusion; and 5, 10, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.</time_frame>
        <population>Pharmacokinetic (PK) Set: All patients that received at least two melflufen doses of 40 mg and had sufficient PK samples taken at Cycle 1 and 2 for determination of all PK variables. One PK sampling series following peripheral administration and one PK sampling series following central administration. Patients with a dose reduction in cycle 2 were not evaluable for PK.</population>
        <group_list>
          <group group_id="O1">
            <title>Peripheral Venous Catheter (PVC)</title>
            <description>Combined treatment ARM for all PVC administration from both ARM A &amp; ARM B during Cycle 1 and 2. Melflufen 40 mg iv Day 1 of each 28-day cycle. Dexamethasone 40 mg po Days 1,8,15 and 22 of each 28-day cycle (20 mg for patients 75 years or older). ARM A Cycle 1 administered via a PVC and Cycle 2 and onwards melflufen administered via a CVC. ARM B Cycle 1 administered via a CVC and Cycle 2 administered via a PVC. From Cycle 3 and onwards melflufen administered via CVC. Melflufen: Peripheral versus central administration. Dexamethasone: Oral tablets.</description>
          </group>
          <group group_id="O2">
            <title>Central Venous Catheter (CVC)</title>
            <description>Combined treatment ARM for all CVC administration from both ARM A &amp; ARM B during Cycle 1 and 2. Melflufen 40 mg iv Day 1 of each 28-day cycle. Dexamethasone 40 mg po Days 1,8,15 and 22 of each 28-day cycle (20 mg for patients 75 years or older). ARM A Cycle 1 administered via a PVC and Cycle 2 and onwards melflufen administered via a CVC. ARM B Cycle 1 administered via a CVC and Cycle 2 administered via a PVC. From Cycle 3 and onwards melflufen administered via CVC. Melflufen: Peripheral versus central administration. Dexamethasone: Oral tablets.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration Versus Time Curve AUC(0-t) of Melphalan</title>
          <description>To evaluate and compare the pharmacokinetic (PK) variable AUC(0-t) of melphalan after central and peripheral intravenous infusion of melflufen.</description>
          <population>Pharmacokinetic (PK) Set: All patients that received at least two melflufen doses of 40 mg and had sufficient PK samples taken at Cycle 1 and 2 for determination of all PK variables. One PK sampling series following peripheral administration and one PK sampling series following central administration. Patients with a dose reduction in cycle 2 were not evaluable for PK.</population>
          <units>min*ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                    <count group_id="O2" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="49518.36" spread="23.710"/>
                    <measurement group_id="O2" value="59543.20" spread="17.698"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="60273.95" spread="30.037"/>
                    <measurement group_id="O2" value="46173.13" spread="43.336"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Based on a geometric mean ratio (GMR) peripheral vs. central of 0.95, a 90% confidence interval (CI) for the ratio of geometric means within bioequivalence limits of 0.8 and 1.25, and 80% power, a sample size of 20 patients (10 per sequence) was required assuming a within-patient variability for period differences (in log scale) of 0.29. Approximately 25 patients were to be enrolled to achieve 20 PK- and local tolerance-evaluable patients.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>The condition for similarity was if the 90% CI for the GMR was within the bioequivalence limits of 0.8 and 1.25.</non_inferiority_desc>
            <param_type>Adjusted geometric mean ratio (GMR)</param_type>
            <param_value>0.952</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.861</ci_lower_limit>
            <ci_upper_limit>1.053</ci_upper_limit>
            <estimate_desc>CVC vs. PVC, where CVC is numerator and PVC is denominator. Linear Mixed Effect Model included terms for period, sequence and administration route (PVC or CVC) as fixed effects and subject nested within sequence as a random effect.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Plasma Concentration Versus Time Curve AUC(0-inf) of Melphalan</title>
        <description>To evaluate and compare the pharmacokinetic (PK) variable AUC(0-inf) of melphalan after central and peripheral intravenous infusion of melflufen</description>
        <time_frame>Cycle 1 Day 1 and Cycle 2 Day 1. Samples were collected 5, 10, 15, 20, and 25 minutes after the start of the infusion; immediately before the end of the infusion; and 5, 10, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.</time_frame>
        <population>Pharmacokinetic (PK) Set: All patients that received at least two melflufen doses of 40 mg and had sufficient PK samples taken at Cycle 1 and 2 for determination of all PK variables. One PK sampling series following peripheral administration and one PK sampling series following central administration. Patients with a dose reduction in cycle 2 were not evaluable for PK.</population>
        <group_list>
          <group group_id="O1">
            <title>Peripheral Venous Catheter (PVC)</title>
            <description>Combined treatment ARM for all PVC administration from both ARM A &amp; ARM B during Cycle 1 and 2. Melflufen 40 mg iv Day 1 of each 28-day cycle. Dexamethasone 40 mg po Days 1,8,15 and 22 of each 28-day cycle (20 mg for patients 75 years or older). ARM A Cycle 1 administered via a PVC and Cycle 2 and onwards melflufen administered via a CVC. ARM B Cycle 1 administered via a CVC and Cycle 2 administered via a PVC. From Cycle 3 and onwards melflufen administered via CVC. Melflufen: Peripheral versus central administration. Dexamethasone: Oral tablets.</description>
          </group>
          <group group_id="O2">
            <title>Central Venous Catheter (CVC)</title>
            <description>Combined treatment ARM for all CVC administration from both ARM A &amp; ARM B during Cycle 1 and 2. Melflufen 40 mg iv Day 1 of each 28-day cycle. Dexamethasone 40 mg po Days 1,8,15 and 22 of each 28-day cycle (20 mg for patients 75 years or older). ARM A Cycle 1 administered via a PVC and Cycle 2 and onwards melflufen administered via a CVC. ARM B Cycle 1 administered via a CVC and Cycle 2 administered via a PVC. From Cycle 3 and onwards melflufen administered via CVC. Melflufen: Peripheral versus central administration. Dexamethasone: Oral tablets.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration Versus Time Curve AUC(0-inf) of Melphalan</title>
          <description>To evaluate and compare the pharmacokinetic (PK) variable AUC(0-inf) of melphalan after central and peripheral intravenous infusion of melflufen</description>
          <population>Pharmacokinetic (PK) Set: All patients that received at least two melflufen doses of 40 mg and had sufficient PK samples taken at Cycle 1 and 2 for determination of all PK variables. One PK sampling series following peripheral administration and one PK sampling series following central administration. Patients with a dose reduction in cycle 2 were not evaluable for PK.</population>
          <units>min*ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                    <count group_id="O2" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="54216.70" spread="23.794"/>
                    <measurement group_id="O2" value="66835.47" spread="18.171"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="67403.07" spread="30.149"/>
                    <measurement group_id="O2" value="50835.59" spread="44.728"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Based on a geometric mean ratio (GMR) peripheral vs. central of 0.95, a 90% confidence interval (CI) for the ratio of geometric means within bioequivalence limits of 0.8 and 1.25, and 80% power, a sample size of 20 patients (10 per sequence) was required assuming a within-patient variability for period differences (in log scale) of 0.29. Approximately 25 patients were to be enrolled to achieve 20 PK- and local tolerance-evaluable patients.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>The condition for similarity was if the 90% CI for the GMR was within the bioequivalence limits of 0.8 and 1.25.</non_inferiority_desc>
            <param_type>Adjusted geometric mean ratio (GMR)</param_type>
            <param_value>0.955</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.863</ci_lower_limit>
            <ci_upper_limit>1.058</ci_upper_limit>
            <estimate_desc>CVC vs. PVC, where CVC is numerator and PVC is denominator. Linear Mixed Effect Model included terms for period, sequence and administration route (PVC or CVC) as fixed effects and subject nested within sequence as a random effect.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Local Reactions Including Phlebitis at Infusion Site After Peripheral Intravenous Administration</title>
        <description>Assessment of the local tolerability of peripheral intravenous administration of melflufen using the Visual Infusion Phlebitis (VIP) scale. The VIP scale provides a score from 0 to 5, noting an ascending order of severity of inflammation. A score of 0 is the lowest possible score, meaning no inflammation detected, and 5 is the highest score, indicating the most severe reaction.</description>
        <time_frame>15 minutes and 4 hours after peripheral intravenous administration, pre- and post-infusion on Day 1 and Day 8</time_frame>
        <population>Safety Analysis Set</population>
        <group_list>
          <group group_id="O1">
            <title>Peripheral Venous Catheter (PVC)</title>
            <description>Combined treatment ARM for all PVC administration from both ARM A &amp; ARM B during Cycle 1 and 2. Melflufen 40 mg iv Day 1 of each 28-day cycle. Dexamethasone 40 mg po Days 1,8,15 and 22 of each 28-day cycle (20 mg for patients 75 years or older). ARM A Cycle 1 administered via a PVC and Cycle 2 and onwards melflufen administered via a CVC. ARM B Cycle 1 administered via a CVC and Cycle 2 administered via a PVC. From Cycle 3 and onwards melflufen administered via CVC. Melflufen: Peripheral versus central administration. Dexamethasone: Oral tablets.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Local Reactions Including Phlebitis at Infusion Site After Peripheral Intravenous Administration</title>
          <description>Assessment of the local tolerability of peripheral intravenous administration of melflufen using the Visual Infusion Phlebitis (VIP) scale. The VIP scale provides a score from 0 to 5, noting an ascending order of severity of inflammation. A score of 0 is the lowest possible score, meaning no inflammation detected, and 5 is the highest score, indicating the most severe reaction.</description>
          <population>Safety Analysis Set</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="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1 Day 1 Pre-Infusion</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>VIP score = 0</title>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>VIP score = 1</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>VIP score = 2</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>VIP score = 3</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>VIP score = 4</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>VIP score = 5</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 1 Day 1 Post-Infusion</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>VIP score = 0</title>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>VIP score = 1</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>VIP score = 2</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>VIP score = 3</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>VIP score = 4</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>VIP score = 5</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 1 Day 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>VIP score = 0</title>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>VIP score = 1</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>VIP score = 2</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>VIP score = 3</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>VIP score = 4</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>VIP score = 5</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2 Day 1 Pre-Infusion</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>VIP score = 0</title>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>VIP score = 1</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>VIP score = 2</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>VIP score = 3</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>VIP score = 4</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>VIP score = 5</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Peak Plasma Concentration for Melflufen and Desethyl-melflufen</title>
        <description>To evaluate and compare the pharmacokinetic (PK) variable Cmax of melflufen and desethyl-melflufen after central and peripheral intravenous infusion of melflufen.</description>
        <time_frame>Cycle 1 Day 1 and Cycle 2 Day 1 - 13 PK samples during and post infusion (28 days cycle)</time_frame>
        <population>Pharmacokinetic (PK) Analysis set: All patients that received at least two melflufen doses of 40 mg and had sufficient PK samples taken at Cycle 1 and 2 for determination of all PK variables. One PK sampling series following peripheral administration and one PK sampling series following central administration. Patients with a dose reduction in cycle 2 were not evaluable for PK.</population>
        <group_list>
          <group group_id="O1">
            <title>Peripheral Venous Catheter (PVC)</title>
            <description>Combined treatment ARM for all PVC administration from both ARM A &amp; ARM B during Cycle 1 and 2. Melflufen 40 mg iv Day 1 of each 28-day cycle. Dexamethasone 40 mg po Days 1,8,15 and 22 of each 28-day cycle (20 mg for patients 75 years or older). ARM A Cycle 1 administered via a PVC and Cycle 2 and onwards melflufen administered via a CVC. ARM B Cycle 1 administered via a CVC and Cycle 2 administered via a PVC. From Cycle 3 and onwards melflufen administered via CVC. Melflufen: Peripheral versus central administration. Dexamethasone: Oral tablets.</description>
          </group>
          <group group_id="O2">
            <title>Central Venous Catheter (CVC)</title>
            <description>Combined treatment ARM for all CVC administration from both ARM A &amp; ARM B during Cycle 1 and 2. Melflufen 40 mg iv Day 1 of each 28-day cycle. Dexamethasone 40 mg po Days 1,8,15 and 22 of each 28-day cycle (20 mg for patients 75 years or older). ARM A Cycle 1 administered via a PVC and Cycle 2 and onwards melflufen administered via a CVC. ARM B Cycle 1 administered via a CVC and Cycle 2 administered via a PVC. From Cycle 3 and onwards melflufen administered via CVC. Melflufen: Peripheral versus central administration. Dexamethasone: Oral tablets.</description>
          </group>
        </group_list>
        <measure>
          <title>Peak Plasma Concentration for Melflufen and Desethyl-melflufen</title>
          <description>To evaluate and compare the pharmacokinetic (PK) variable Cmax of melflufen and desethyl-melflufen after central and peripheral intravenous infusion of melflufen.</description>
          <population>Pharmacokinetic (PK) Analysis set: All patients that received at least two melflufen doses of 40 mg and had sufficient PK samples taken at Cycle 1 and 2 for determination of all PK variables. One PK sampling series following peripheral administration and one PK sampling series following central administration. Patients with a dose reduction in cycle 2 were not evaluable for PK.</population>
          <units>ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Melflufen Cycle 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                    <count group_id="O2" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="151.11" spread="59.74"/>
                    <measurement group_id="O2" value="123.0" spread="47.498"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Melflufen Cycle 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="127.27" spread="75.872"/>
                    <measurement group_id="O2" value="141.75" spread="47.921"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Desethyl-melflufen Cycle 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                    <count group_id="O2" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.721" spread="33.2618"/>
                    <measurement group_id="O2" value="11.851" spread="41.3587"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Desethyl-melflufen Cycle 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.801" spread="43.8965"/>
                    <measurement group_id="O2" value="11.851" spread="41.3587"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>For melflufen: Based on a geometric mean ratio (GMR) peripheral vs central of 0.95, a 90% confidence interval (CI) for the ratio of geometric means within bioequivalence limits of 0.8 and 1.25, and 80% power, a sample size of 20 patients (10 per sequence) was required assuming a within-patient variability for period differences (in log scale) of 0.29. Approximately 25 patients were to be enrolled to achieve 20 PK- and local tolerance-evaluable patients.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>The condition for similarity was if the 90% CI for the GMR was within the bioequivalence limits of 0.8 and 1.25.</non_inferiority_desc>
            <param_type>adjusted geometric mean ratio (GMR)</param_type>
            <param_value>0.948</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.736</ci_lower_limit>
            <ci_upper_limit>1.222</ci_upper_limit>
            <estimate_desc>CVC vs PVC CVC is numerator and PVC is denominator. Linear Mixed Effect Model included terms for period, sequence and administration route (PVC or CVC) as fixed effects and subject nested within sequence as a random effect.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>For desmethyl-melflufen: Based on a geometric mean ratio (GMR) peripheral vs central of 0.95, a 90% confidence interval (CI) for the ratio of geometric means within bioequivalence limits of 0.8 and 1.25, and 80% power, a sample size of 20 patients (10 per sequence) was required assuming a within-patient variability for period differences (in log scale) of 0.29. Approximately 25 patients were to be enrolled to achieve 20 PK- and local tolerance-evaluable patients.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>The condition for similarity was if the 90% CI for the GMR was within the bioequivalence limits of 0.8 and 1.25.</non_inferiority_desc>
            <param_type>[adjusted geometric mean ratio (GMR)]</param_type>
            <param_value>0.846</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.748</ci_lower_limit>
            <ci_upper_limit>0.957</ci_upper_limit>
            <estimate_desc>CVC vs PVC CVC is numerator and PVC is denominator. Linear Mixed Effect Model included terms for period, sequence and administration route (PVC or CVC) as fixed effects and subject nested within sequence as a random effect.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Plasma Concentration Versus Time Curve AUC(0-t) of Melflufen and Desethyl-melflufen</title>
        <description>To evaluate and compare the pharmacokinetic (PK) variable AUC(0-t) of melflufen and desethyl-melflufen after central and peripheral intravenous infusion of melflufen</description>
        <time_frame>Cycle 1 Day 1 and Cycle 2 Day 1 - 13 PK samples during and post infusion (28 days cycle)</time_frame>
        <population>Pharmacokinetic (PK) analysis set: All patients that received at least two melflufen doses of 40 mg and had sufficient PK samples taken at Cycle 1 and 2 for determination of all PK variables. One PK sampling series following peripheral administration and one PK sampling series following central administration. Patients with a dose reduction in cycle 2 were not evaluable for PK.</population>
        <group_list>
          <group group_id="O1">
            <title>Peripheral Venous Catheter (PVC)</title>
            <description>Combined treatment ARM for all PVC administration from both ARM A &amp; ARM B during Cycle 1 and 2. Melflufen 40 mg iv Day 1 of each 28-day cycle. Dexamethasone 40 mg po Days 1,8,15 and 22 of each 28-day cycle (20 mg for patients 75 years or older). ARM A Cycle 1 administered via a PVC and Cycle 2 and onwards melflufen administered via a CVC. ARM B Cycle 1 administered via a CVC and Cycle 2 administered via a PVC. From Cycle 3 and onwards melflufen administered via CVC. Melflufen: Peripheral versus central administration. Dexamethasone: Oral tablets.</description>
          </group>
          <group group_id="O2">
            <title>Central Venous Catheter (CVC)</title>
            <description>Combined treatment ARM for all CVC administration from both ARM A &amp; ARM B during Cycle 1 and 2. Melflufen 40 mg iv Day 1 of each 28-day cycle. Dexamethasone 40 mg po Days 1,8,15 and 22 of each 28-day cycle (20 mg for patients 75 years or older). ARM A Cycle 1 administered via a PVC and Cycle 2 and onwards melflufen administered via a CVC. ARM B Cycle 1 administered via a CVC and Cycle 2 administered via a PVC. From Cycle 3 and onwards melflufen administered via CVC. Melflufen: Peripheral versus central administration. Dexamethasone: Oral tablets.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration Versus Time Curve AUC(0-t) of Melflufen and Desethyl-melflufen</title>
          <description>To evaluate and compare the pharmacokinetic (PK) variable AUC(0-t) of melflufen and desethyl-melflufen after central and peripheral intravenous infusion of melflufen</description>
          <population>Pharmacokinetic (PK) analysis set: All patients that received at least two melflufen doses of 40 mg and had sufficient PK samples taken at Cycle 1 and 2 for determination of all PK variables. One PK sampling series following peripheral administration and one PK sampling series following central administration. Patients with a dose reduction in cycle 2 were not evaluable for PK.</population>
          <units>min x ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Melflufen Cycle 1 (0-t)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                    <count group_id="O2" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3617.03" spread="52.244"/>
                    <measurement group_id="O2" value="2828.69" spread="51.646"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Melflufen Cycle 2 (0-t)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3083.74" spread="80.639"/>
                    <measurement group_id="O2" value="3078.21" spread="49.443"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Desethyl-melflufen Cycle 1 (0-t)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                    <count group_id="O2" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="563.34" spread="42.086"/>
                    <measurement group_id="O2" value="639.39" spread="34.053"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Desethyl-melflufen Cycle 2 (0-t)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="636.06" spread="51.627"/>
                    <measurement group_id="O2" value="391.11" spread="49.458"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Based on a geometric mean ratio (GMR) peripheral vs central of 0.95, a 90% confidence interval (CI) for the ratio of geometric means within bioequivalence limits of 0.8 and 1.25, and 80% power, a sample size of 20 patients (10 per sequence) was required assuming a within-patient variability for period differences (in log scale) of 0.29. Approximately 25 patients were to be enrolled to achieve 20 PK- and local tolerance-evaluable patients.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>The condition for similarity was if the 90% CI for the GMR was within the bioequivalence limits of 0.8 and 1.25.</non_inferiority_desc>
            <param_type>adjusted geometric mean ratio (GMR)</param_type>
            <param_value>0.877</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.684</ci_lower_limit>
            <ci_upper_limit>1.126</ci_upper_limit>
            <estimate_desc>Data above refer to meflufen. CVC vs PVC CVC is numerator, PVC is denominator. Linear Mixed Effect Model included terms for period, sequence and administration route (PVC or CVC) as fixed effects and subject nested within sequence as a random effect.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Based on a geometric mean ratio (GMR) peripheral vs central of 0.95, a 90% confidence interval (CI) for the ratio of geometric means within bioequivalence limits of 0.8 and 1.25, and 80% power, a sample size of 20 patients (10 per sequence) was required assuming a within-patient variability for period differences (in log scale) of 0.29. Approximately 25 patients were to be enrolled to achieve 20 PK- and local tolerance-evaluable patients.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>The condition for similarity was if the 90% CI for the GMR was within the bioequivalence limits of 0.8 and 1.25.</non_inferiority_desc>
            <param_type>adjusted geometric mean ratio (GMR)</param_type>
            <param_value>0.897</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.819</ci_lower_limit>
            <ci_upper_limit>0.982</ci_upper_limit>
            <estimate_desc>Data above refer to desethyl-melflufen. CVC vs PVC CVC is numerator, PVC is denominator. Linear Mixed Effect Model included terms for period, sequence and administration route as fixed effects and subject nested within sequence as a random effect.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Plasma Concentration Versus Time Curve AUC(0-inf) of Melflufen and Desethyl-melflufen</title>
        <description>To evaluate and compare the pharmacokinetic (PK) variable AUC(0-inf) of melflufen and desethyl-melflufen after central and peripheral intravenous infusion of melflufen</description>
        <time_frame>Cycle 1 Day 1 and Cycle 2 Day 1 - 13 PK samples during and post infusion (28 days cycle)</time_frame>
        <population>Pharmacokinetic (PK) Analysis set: All patients that received at least two melflufen doses of 40 mg and had sufficient PK samples taken at Cycle 1 and 2 for determination of all PK variables. One PK sampling series following peripheral administration and one PK sampling series following central administration. Patients with a dose reduction in Cycle 2 were not evaluable for PK.</population>
        <group_list>
          <group group_id="O1">
            <title>Peripheral Venous Catheter (PVC)</title>
            <description>Combined treatment ARM for all PVC administration from both ARM A &amp; ARM B during Cycle 1 and 2. Melflufen 40 mg iv Day 1 of each 28-day cycle. Dexamethasone 40 mg po Days 1,8,15 and 22 of each 28-day cycle (20 mg for patients 75 years or older). ARM A Cycle 1 administered via a PVC and Cycle 2 and onwards melflufen administered via a CVC. ARM B Cycle 1 administered via a CVC and Cycle 2 administered via a PVC. From Cycle 3 and onwards melflufen administered via CVC. Melflufen: Peripheral versus central administration. Dexamethasone: Oral tablets.</description>
          </group>
          <group group_id="O2">
            <title>Central Venous Catheter (CVC)</title>
            <description>Combined treatment ARM for all CVC administration from both ARM A &amp; ARM B during Cycle 1 and 2. Melflufen 40 mg iv Day 1 of each 28-day cycle. Dexamethasone 40 mg po Days 1,8,15 and 22 of each 28-day cycle (20 mg for patients 75 years or older). ARM A Cycle 1 administered via a PVC and Cycle 2 and onwards melflufen administered via a CVC. ARM B Cycle 1 administered via a CVC and Cycle 2 administered via a PVC. From Cycle 3 and onwards melflufen administered via CVC. Melflufen: Peripheral versus central administration. Dexamethasone: Oral tablets.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration Versus Time Curve AUC(0-inf) of Melflufen and Desethyl-melflufen</title>
          <description>To evaluate and compare the pharmacokinetic (PK) variable AUC(0-inf) of melflufen and desethyl-melflufen after central and peripheral intravenous infusion of melflufen</description>
          <population>Pharmacokinetic (PK) Analysis set: All patients that received at least two melflufen doses of 40 mg and had sufficient PK samples taken at Cycle 1 and 2 for determination of all PK variables. One PK sampling series following peripheral administration and one PK sampling series following central administration. Patients with a dose reduction in Cycle 2 were not evaluable for PK.</population>
          <units>min x ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Melflufen Cycle 1 (0-inf)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                    <count group_id="O2" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3639.34" spread="52.379"/>
                    <measurement group_id="O2" value="2841.23" spread="51.631"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Meflufen Cycle 2 (0-inf)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3099.70" spread="80.708"/>
                    <measurement group_id="O2" value="3093.96" spread="49.295"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Desethyl-melflufen Cycle 1 (0-inf)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                    <count group_id="O2" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="609.44" spread="40.778"/>
                    <measurement group_id="O2" value="759.25" spread="34.619"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Desethyl-melflufen Cycle 2 (0-inf)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="695.29" spread="51.722"/>
                    <measurement group_id="O2" value="440.65" spread="43.547"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Based on a geometric mean ratio (GMR) peripheral vs central of 0.95, a 90% confidence interval (CI) for the ratio of geometric means within bioequivalence limits of 0.8 and 1.25, and 80% power, a sample size of 20 patients (10 per sequence) was required assuming a within-patient variability for period differences (in log scale) of 0.29. Approximately 25 patients were to be enrolled to achieve 20 PK- and local tolerance-evaluable patients.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>The condition for similarity was if the 90% CI for the GMR was within the bioequivalence limits of 0.8 and 1.25.</non_inferiority_desc>
            <param_type>adjusted geometric mean ratio (GMR)</param_type>
            <param_value>0.877</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.684</ci_lower_limit>
            <ci_upper_limit>1.124</ci_upper_limit>
            <estimate_desc>Data above refer to melflufen. CVC vs PVC CVC is numerator, PVC is denominator. Linear Mixed Effect Model included terms for period, sequence &amp; administration route (PVC or CVC) as fixed effects and subject nested within sequence as a random effect.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Based on a geometric mean ratio (GMR) peripheral vs central of 0.95, a 90% confidence interval (CI) for the ratio of geometric means within bioequivalence limits of 0.8 and 1.25, and 80% power, a sample size of 20 patients (10 per sequence) was required assuming a within-patient variability for period differences (in log scale) of 0.29. Approximately 25 patients were to be enrolled to achieve 20 PK- and local tolerance-evaluable patients.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>The condition for similarity was if the 90% CI for the GMR was within the bioequivalence limits of 0.8 and 1.25.</non_inferiority_desc>
            <param_type>adjusted geometric mean ratio (GMR)</param_type>
            <param_value>0.908</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.833</ci_lower_limit>
            <ci_upper_limit>0.989</ci_upper_limit>
            <estimate_desc>Data above refer to desethyl-melflufen. CVC vs PVC CVC is numerator, PVC is denominator. Linear Mixed Effect Model included terms for period, sequence &amp; administration route as fixed effects and subject nested within sequence as a random effect.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Elimination Half-life (t1/2) of Melflufen, Melphalan and Desethyl-melflufen</title>
        <description>To evaluate elimination half-life (t½) for melflufen, melphalan and desethyl-melflufen after central and peripheral intravenous infusion of melflufen.</description>
        <time_frame>Cycle 1 Day 1 and Cycle 2 Day 1 - 13 measurements during and post infusion (28 days cycle)</time_frame>
        <population>Pharmacokinetic (PK) Analysis set:All patients that received at least two melflufen doses of 40 mg and had sufficient PK samples taken at Cycle 1 and 2 for determination of all PK variables. One PK sampling series following peripheral administration and one PK sampling series following central administration. Patients with a dose reduction in cycle 2 were not evaluable for PK.</population>
        <group_list>
          <group group_id="O1">
            <title>Peripheral Venous Catheter (PVC)</title>
            <description>Combined treatment ARM for all PVC administration from both ARM A &amp; ARM B during Cycle 1 and 2. Melflufen 40 mg iv Day 1 of each 28-day cycle. Dexamethasone 40 mg po Days 1,8,15 and 22 of each 28-day cycle (20 mg for patients 75 years or older). ARM A Cycle 1 administered via a PVC and Cycle 2 and onwards melflufen administered via a CVC. ARM B Cycle 1 administered via a CVC and Cycle 2 administered via a PVC. From Cycle 3 and onwards melflufen administered via CVC. Melflufen: Peripheral versus central administration. Dexamethasone: Oral tablets.</description>
          </group>
          <group group_id="O2">
            <title>Central Venous Catheter (CVC)</title>
            <description>Combined treatment ARM for all CVC administration from both ARM A &amp; ARM B during Cycle 1 and 2. Melflufen 40 mg iv Day 1 of each 28-day cycle. Dexamethasone 40 mg po Days 1,8,15 and 22 of each 28-day cycle (20 mg for patients 75 years or older). ARM A Cycle 1 administered via a PVC and Cycle 2 and onwards melflufen administered via a CVC. ARM B Cycle 1 administered via a CVC and Cycle 2 administered via a PVC. From Cycle 3 and onwards melflufen administered via CVC. Melflufen: Peripheral versus central administration. Dexamethasone: Oral tablets.</description>
          </group>
        </group_list>
        <measure>
          <title>Elimination Half-life (t1/2) of Melflufen, Melphalan and Desethyl-melflufen</title>
          <description>To evaluate elimination half-life (t½) for melflufen, melphalan and desethyl-melflufen after central and peripheral intravenous infusion of melflufen.</description>
          <population>Pharmacokinetic (PK) Analysis set:All patients that received at least two melflufen doses of 40 mg and had sufficient PK samples taken at Cycle 1 and 2 for determination of all PK variables. One PK sampling series following peripheral administration and one PK sampling series following central administration. Patients with a dose reduction in cycle 2 were not evaluable for PK.</population>
          <units>minutes</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Melphalan Cycle 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                    <count group_id="O2" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="72.51" spread="14.993"/>
                    <measurement group_id="O2" value="80.09" spread="12.85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Melphalan Cycle 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="78.09" spread="18.118"/>
                    <measurement group_id="O2" value="72.97" spread="16.84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Melflufen Cycle 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                    <count group_id="O2" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.42" spread="106.832"/>
                    <measurement group_id="O2" value="4.45" spread="90.634"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Melflufen Cycle 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.15" spread="81.278"/>
                    <measurement group_id="O2" value="5.74" spread="80.837"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Desethyl-melflufen Cycle 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                    <count group_id="O2" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.44" spread="49.68"/>
                    <measurement group_id="O2" value="23.49" spread="43.423"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Desethyl-melflufen Cycle 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25.04" spread="83.298"/>
                    <measurement group_id="O2" value="17.43" spread="37.708"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Frequency of Treatment-Emergent Adverse Events (TEAEs) by MedDRA SOC and PT</title>
        <description>To assess safety and general tolerability of melflufen by collecting non-serious Adverse Events (AEs) from the start of study treatment until 30 days after the last dose of any study drug (melflufen or dexamethasone) or initiation of subsequent therapy whichever occurred first. Serious AEs (SAEs) were collected from the time the subject signed the ICF until 30 days after the last dose of any study drug (melflufen or dexamethasone) or initiation of subsequent therapy whichever occurred first.</description>
        <time_frame>Median treatment durations for Arm A and Arm B were 29.14 weeks and 12.14 weeks, respectively. The AE reporting period is estimated to be 30 days longer.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm A</title>
            <description>Melflufen 40 mg iv Day 1 of each 28 day cycle. Dexamethasone 40 mg po Day 1,8, 15 and 22 of each 28 day cycle, if &gt; 75 years of age 20 mg. Cycle 1 will be administered via a Peripheral Venous Catheter (PVC) and cycle 2 and onwards melflufen will be administered via a Central Venous Catheter (CVC).&#xD;
Melphalan: Peripheral versus central administration&#xD;
Dexamethasone: Oral tablets</description>
          </group>
          <group group_id="O2">
            <title>Arm B</title>
            <description>Melflufen 40 mg iv Day 1 of each 28 day cycle. Dexamethasone 40 mg po Day 1,8, 15 and 22 of each 28 day cycle, if &gt; 75 years of age 20 mg. Cycle 1 will be administered via a Central Venous Catheter (CVC) and cycle 2 will be administered via a Peripheral Venous Catheter (PVC). From cycle 3 and onwards melflufen will be administered via CVC.&#xD;
Melphalan: Peripheral versus central administration&#xD;
Dexamethasone: Oral tablets</description>
          </group>
          <group group_id="O3">
            <title>Overall</title>
            <description>Arm A plus Arm B</description>
          </group>
        </group_list>
        <measure>
          <title>Frequency of Treatment-Emergent Adverse Events (TEAEs) by MedDRA SOC and PT</title>
          <description>To assess safety and general tolerability of melflufen by collecting non-serious Adverse Events (AEs) from the start of study treatment until 30 days after the last dose of any study drug (melflufen or dexamethasone) or initiation of subsequent therapy whichever occurred first. Serious AEs (SAEs) were collected from the time the subject signed the ICF until 30 days after the last dose of any study drug (melflufen or dexamethasone) or initiation of subsequent therapy whichever occurred first.</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="14"/>
                <count group_id="O2" value="13"/>
                <count group_id="O3" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Patients with at least 1 TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                    <measurement group_id="O2" value="13"/>
                    <measurement group_id="O3" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Blood and lymphatic system disorders</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                    <measurement group_id="O2" value="12"/>
                    <measurement group_id="O3" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Thrombocytopenia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="10"/>
                    <measurement group_id="O3" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Neutropenia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="9"/>
                    <measurement group_id="O3" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Anaemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="7"/>
                    <measurement group_id="O3" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Leukopenia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Infections and Infestations</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="7"/>
                    <measurement group_id="O3" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pneumonia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>COVID-19 pneumonia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Respiratory tract infection</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>General disorders and administration site conditions</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="6"/>
                    <measurement group_id="O3" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pyrexia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Fatigue</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>General health deterioration</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Musculoskeletal and connective tissue disorders</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="5"/>
                    <measurement group_id="O3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Arthralgia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Back pain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Bone pain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Investigations</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="4"/>
                    <measurement group_id="O3" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SARS-CoV-2 test positive</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="4"/>
                    <measurement group_id="O3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>C-reactive protein increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Injury, poisoning and procedural complications</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>femur fracture</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Skin and subcutaneous tissue disorders</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Rash</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Best Response (Stringent Complete Response (sCR), Complete Response (CR), Very Good Partial Response (VGPR), Partial Response (PR), Minimal Response (MR), Stable Disease (SD) or Progressive Disease (PD)</title>
        <description>To assess best response during the study with the criteria established by the International Myeloma Working Group Uniform Response Criteria (IMWG-URC) for sCR, CR, VGPR, PR, SD and PD</description>
        <time_frame>From initiation of therapy until disease progression. Median treatment durations for Arm A and Arm B were 29.14 weeks and 12.14 weeks, respectively.</time_frame>
        <population>Full Analysis Set: 14 participants randomized to Arm A and 13 participants randomized to Arm B.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm A</title>
            <description>Melflufen 40 mg iv Day 1 of each 28 day cycle. Dexamethasone 40 mg po Day 1,8, 15 and 22 of each 28 day cycle, if &gt; 75 years of age 20 mg. Cycle 1 will be administered via a Peripheral Venous Catheter (PVC) and cycle 2 and onwards melflufen will be administered via a Central Venous Catheter (CVC).&#xD;
Melphalan: Peripheral versus central administration&#xD;
Dexamethasone: Oral tablets</description>
          </group>
          <group group_id="O2">
            <title>Arm B</title>
            <description>Melflufen 40 mg iv Day 1 of each 28 day cycle. Dexamethasone 40 mg po Day 1,8, 15 and 22 of each 28 day cycle, if &gt; 75 years of age 20 mg. Cycle 1 will be administered via a Central Venous Catheter (CVC) and cycle 2 will be administered via a Peripheral Venous Catheter (PVC). From cycle 3 and onwards melflufen will be administered via CVC.&#xD;
Melphalan: Peripheral versus central administration&#xD;
Dexamethasone: Oral tablets</description>
          </group>
          <group group_id="O3">
            <title>Overall</title>
            <description>Arm A plus Arm B</description>
          </group>
        </group_list>
        <measure>
          <title>Best Response (Stringent Complete Response (sCR), Complete Response (CR), Very Good Partial Response (VGPR), Partial Response (PR), Minimal Response (MR), Stable Disease (SD) or Progressive Disease (PD)</title>
          <description>To assess best response during the study with the criteria established by the International Myeloma Working Group Uniform Response Criteria (IMWG-URC) for sCR, CR, VGPR, PR, SD and PD</description>
          <population>Full Analysis Set: 14 participants randomized to Arm A and 13 participants randomized to Arm B.</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="14"/>
                <count group_id="O2" value="13"/>
                <count group_id="O3" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Stringent complete response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Complete response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Very good partial response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Partial response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Minimal response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Stable disease</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="6"/>
                    <measurement group_id="O3" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Progressive disease</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Not available</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="4"/>
                    <measurement group_id="O3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>ORR</title>
        <description>To assess overall response rate (ORR), including CR/sCR, VGPR and PR, during the study with the criteria established by the IMWG-URC.</description>
        <time_frame>From initiation of therapy until disease progression. Maximum treatment durations for Arm A and Arm B were 68.4 and 59.0 weeks, respectively.</time_frame>
        <population>Full Analysis set: 14 participants randomized to Arm A and 13 participants randomized to Arm B.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm A</title>
            <description>Melflufen 40 mg iv Day 1 of each 28 day cycle. Dexamethasone 40 mg po Day 1,8, 15 and 22 of each 28 day cycle, if &gt; 75 years of age 20 mg. Cycle 1 will be administered via a Peripheral Venous Catheter (PVC) and cycle 2 and onwards melflufen will be administered via a Central Venous Catheter (CVC).&#xD;
Melphalan: Peripheral versus central administration&#xD;
Dexamethasone: Oral tablets</description>
          </group>
          <group group_id="O2">
            <title>Arm B</title>
            <description>Melflufen 40 mg iv Day 1 of each 28 day cycle. Dexamethasone 40 mg po Day 1,8, 15 and 22 of each 28 day cycle, if &gt; 75 years of age 20 mg. Cycle 1 will be administered via a Central Venous Catheter (CVC) and cycle 2 will be administered via a Peripheral Venous Catheter (PVC). From cycle 3 and onwards melflufen will be administered via CVC.&#xD;
Melphalan: Peripheral versus central administration&#xD;
Dexamethasone: Oral tablets</description>
          </group>
          <group group_id="O3">
            <title>Overall</title>
            <description>Arm A plus Arm B</description>
          </group>
        </group_list>
        <measure>
          <title>ORR</title>
          <description>To assess overall response rate (ORR), including CR/sCR, VGPR and PR, during the study with the criteria established by the IMWG-URC.</description>
          <population>Full Analysis set: 14 participants randomized to Arm A and 13 participants randomized to Arm B.</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="14"/>
                <count group_id="O2" value="13"/>
                <count group_id="O3" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>CBR</title>
        <description>To assess clinical benefit rate (CBR), i.e., proportion of patients that achieve a confirmed minimal response or better (sCR, CR, VGPR, PR and MR), during the study with the criteria established by the IMWG-URC.</description>
        <time_frame>To be assessed at the end of study drug treatment. Maximum treatment durations for Arm A and Arm B were 68.4 and 59.0 weeks, respectively.</time_frame>
        <population>Full Analysis set: 14 participants randomized to Arm A and 13 participants randomized to Arm B.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm A</title>
            <description>Melflufen 40 mg iv Day 1 of each 28 day cycle. Dexamethasone 40 mg po Day 1,8, 15 and 22 of each 28 day cycle, if &gt; 75 years of age 20 mg. Cycle 1 will be administered via a Peripheral Venous Catheter (PVC) and cycle 2 and onwards melflufen will be administered via a Central Venous Catheter (CVC).&#xD;
Melphalan: Peripheral versus central administration&#xD;
Dexamethasone: Oral tablets</description>
          </group>
          <group group_id="O2">
            <title>Arm B</title>
            <description>Melflufen 40 mg iv Day 1 of each 28 day cycle. Dexamethasone 40 mg po Day 1,8, 15 and 22 of each 28 day cycle, if &gt; 75 years of age 20 mg. Cycle 1 will be administered via a Central Venous Catheter (CVC) and cycle 2 will be administered via a Peripheral Venous Catheter (PVC). From cycle 3 and onwards melflufen will be administered via CVC.&#xD;
Melphalan: Peripheral versus central administration&#xD;
Dexamethasone: Oral tablets</description>
          </group>
          <group group_id="O3">
            <title>Overall</title>
            <description>Arm A plus Arm B</description>
          </group>
        </group_list>
        <measure>
          <title>CBR</title>
          <description>To assess clinical benefit rate (CBR), i.e., proportion of patients that achieve a confirmed minimal response or better (sCR, CR, VGPR, PR and MR), during the study with the criteria established by the IMWG-URC.</description>
          <population>Full Analysis set: 14 participants randomized to Arm A and 13 participants randomized to Arm B.</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="14"/>
                <count group_id="O2" value="13"/>
                <count group_id="O3" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>DOR</title>
        <description>To assess duration of response (DOR): the time in months from the first evidence of confirmed assessment of sCR, CR, VGPR, or PR to first confirmed disease progression according to the criteria established by the IMWG-URC or to death due to any cause. DOR is defined only for patients with a confirmed PR or better.</description>
        <time_frame>From confirmed response until disease progression. Maximum treatment durations for Arm A and Arm B were 68.4 and 59.0 weeks, respectively.</time_frame>
        <population>Full Analysis set: 14 participants randomized to Arm A and 13 participants randomized to Arm B.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm A</title>
            <description>Melflufen 40 mg iv Day 1 of each 28 day cycle. Dexamethasone 40 mg po Day 1,8, 15 and 22 of each 28 day cycle, if &gt; 75 years of age 20 mg. Cycle 1 will be administered via a Peripheral Venous Catheter (PVC) and cycle 2 and onwards melflufen will be administered via a Central Venous Catheter (CVC).&#xD;
Melphalan: Peripheral versus central administration&#xD;
Dexamethasone: Oral tablets</description>
          </group>
          <group group_id="O2">
            <title>Arm B</title>
            <description>Melflufen 40 mg iv Day 1 of each 28 day cycle. Dexamethasone 40 mg po Day 1,8, 15 and 22 of each 28 day cycle, if &gt; 75 years of age 20 mg. Cycle 1 will be administered via a Central Venous Catheter (CVC) and cycle 2 will be administered via a Peripheral Venous Catheter (PVC). From cycle 3 and onwards melflufen will be administered via CVC.&#xD;
Melphalan: Peripheral versus central administration&#xD;
Dexamethasone: Oral tablets</description>
          </group>
          <group group_id="O3">
            <title>Overall</title>
            <description>Arm A plus Arm B</description>
          </group>
        </group_list>
        <measure>
          <title>DOR</title>
          <description>To assess duration of response (DOR): the time in months from the first evidence of confirmed assessment of sCR, CR, VGPR, or PR to first confirmed disease progression according to the criteria established by the IMWG-URC or to death due to any cause. DOR is defined only for patients with a confirmed PR or better.</description>
          <population>Full Analysis set: 14 participants randomized to Arm A and 13 participants randomized to Arm B.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="13"/>
                <count group_id="O3" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="1.18" upper_limit="NA">Note: At study termination, the DOR data was insufficient to evaluate due to the low number of patient events: 1 (7.1%) in Arm A, 0 in Arm B.</measurement>
                    <measurement group_id="O2" value="NA" lower_limit="NA" upper_limit="NA">Note: At study termination, the DOR data was insufficient to evaluate due to the low number of patient events: 1 (7.1%) in Arm A, 0 in Arm B.</measurement>
                    <measurement group_id="O3" value="NA" lower_limit="1.18" upper_limit="NA">Note: At study termination, the DOR data was insufficient to evaluate due to the low number of patient events: 1 (7.1%) in Arm A, 0 in Arm B.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>DOCB</title>
        <description>To assess duration of clinical benefit (DOCB) in patients with stringent complete response (sCR), complete response (CR), very good partial response (VGPR), PR, or MR during the study with the criteria established by the IMWG-URC.</description>
        <time_frame>From first evidence of confirmed assessment of sCR, CR, VGPR, PR or MR to first confirmed disease progression, or to death due to any cause. Maximum treatment durations for Arm A and Arm B were 68.4 and 59.0 weeks, respectively.</time_frame>
        <population>Full Analysis set: 14 participants randomized to Arm A and 13 participants randomized to Arm B.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm A</title>
            <description>Melflufen 40 mg iv Day 1 of each 28 day cycle. Dexamethasone 40 mg po Day 1,8, 15 and 22 of each 28 day cycle, if &gt; 75 years of age 20 mg. Cycle 1 will be administered via a Peripheral Venous Catheter (PVC) and cycle 2 and onwards melflufen will be administered via a Central Venous Catheter (CVC).&#xD;
Melphalan: Peripheral versus central administration&#xD;
Dexamethasone: Oral tablets</description>
          </group>
          <group group_id="O2">
            <title>Arm B</title>
            <description>Melflufen 40 mg iv Day 1 of each 28 day cycle. Dexamethasone 40 mg po Day 1,8, 15 and 22 of each 28 day cycle, if &gt; 75 years of age 20 mg. Cycle 1 will be administered via a Central Venous Catheter (CVC) and cycle 2 will be administered via a Peripheral Venous Catheter (PVC). From cycle 3 and onwards melflufen will be administered via CVC.&#xD;
Melphalan: Peripheral versus central administration&#xD;
Dexamethasone: Oral tablets</description>
          </group>
          <group group_id="O3">
            <title>Overall</title>
            <description>Arm A plus Arm B</description>
          </group>
        </group_list>
        <measure>
          <title>DOCB</title>
          <description>To assess duration of clinical benefit (DOCB) in patients with stringent complete response (sCR), complete response (CR), very good partial response (VGPR), PR, or MR during the study with the criteria established by the IMWG-URC.</description>
          <population>Full Analysis set: 14 participants randomized to Arm A and 13 participants randomized to Arm B.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="13"/>
                <count group_id="O3" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="3.02" upper_limit="NA">Overall, 3 patients had experienced an event and 7 had been censored, as they were alive and without a PD assessment at the time of study termination. Consequently, the DOCB data was insufficient to evaluate.</measurement>
                    <measurement group_id="O2" value="NA" lower_limit="NA" upper_limit="NA">Overall, 3 patients had experienced an event and 7 had been censored, as they were alive and without a PD assessment at the time of study termination. Consequently, the DOCB data was insufficient to evaluate.</measurement>
                    <measurement group_id="O3" value="NA" lower_limit="7.16" upper_limit="NA">Overall, 3 patients had experienced an event and 7 had been censored, as they were alive and without a PD assessment at the time of study termination. Consequently, the DOCB data was insufficient to evaluate.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>TTR</title>
        <description>To assess time to response (TTR) in patients with PR or better during the study with the criteria established by the UMWG-URC.</description>
        <time_frame>From initiation of therapy until documented disease response. Maximum treatment durations for Arm A and Arm B were 68.4 and 59.0 weeks, respectively.</time_frame>
        <population>Full Analysis set:14 participants randomized to Arm A and 13 participants randomized to Arm B.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm A</title>
            <description>Melflufen 40 mg iv Day 1 of each 28 day cycle. Dexamethasone 40 mg po Day 1,8, 15 and 22 of each 28 day cycle, if &gt; 75 years of age 20 mg. Cycle 1 will be administered via a Peripheral Venous Catheter (PVC) and cycle 2 and onwards melflufen will be administered via a Central Venous Catheter (CVC).&#xD;
Melphalan: Peripheral versus central administration&#xD;
Dexamethasone: Oral tablets</description>
          </group>
          <group group_id="O2">
            <title>Arm B</title>
            <description>Melflufen 40 mg iv Day 1 of each 28 day cycle. Dexamethasone 40 mg po Day 1,8, 15 and 22 of each 28 day cycle, if &gt; 75 years of age 20 mg. Cycle 1 will be administered via a Central Venous Catheter (CVC) and cycle 2 will be administered via a Peripheral Venous Catheter (PVC). From cycle 3 and onwards melflufen will be administered via CVC.&#xD;
Melphalan: Peripheral versus central administration&#xD;
Dexamethasone: Oral tablets</description>
          </group>
          <group group_id="O3">
            <title>Overall</title>
            <description>Arm A plus Arm B</description>
          </group>
        </group_list>
        <measure>
          <title>TTR</title>
          <description>To assess time to response (TTR) in patients with PR or better during the study with the criteria established by the UMWG-URC.</description>
          <population>Full Analysis set:14 participants randomized to Arm A and 13 participants randomized to Arm B.</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="14"/>
                <count group_id="O2" value="13"/>
                <count group_id="O3" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>TTP</title>
        <description>To assess time to progression (TTP) during the study with the criteria established by the IMWG-URC.</description>
        <time_frame>From date of randomization until documented disease progression. Maximum treatment durations for Arm A and Arm B were 68.4 and 59.0 weeks, respectively.</time_frame>
        <population>Full Analysis set: 14 participants randomized to Arm A and 13 participants randomized to Arm B.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm A</title>
            <description>Melflufen 40 mg iv Day 1 of each 28 day cycle. Dexamethasone 40 mg po Day 1,8, 15 and 22 of each 28 day cycle, if &gt; 75 years of age 20 mg. Cycle 1 will be administered via a Peripheral Venous Catheter (PVC) and cycle 2 and onwards melflufen will be administered via a Central Venous Catheter (CVC).&#xD;
Melphalan: Peripheral versus central administration&#xD;
Dexamethasone: Oral tablets</description>
          </group>
          <group group_id="O2">
            <title>Arm B</title>
            <description>Melflufen 40 mg iv Day 1 of each 28 day cycle. Dexamethasone 40 mg po Day 1,8, 15 and 22 of each 28 day cycle, if &gt; 75 years of age 20 mg. Cycle 1 will be administered via a Central Venous Catheter (CVC) and cycle 2 will be administered via a Peripheral Venous Catheter (PVC). From cycle 3 and onwards melflufen will be administered via CVC.&#xD;
Melphalan: Peripheral versus central administration&#xD;
Dexamethasone: Oral tablets</description>
          </group>
          <group group_id="O3">
            <title>Overall</title>
            <description>Arm A plus Arm B</description>
          </group>
        </group_list>
        <measure>
          <title>TTP</title>
          <description>To assess time to progression (TTP) during the study with the criteria established by the IMWG-URC.</description>
          <population>Full Analysis set: 14 participants randomized to Arm A and 13 participants randomized to Arm B.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="13"/>
                <count group_id="O3" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.78" lower_limit="2.73" upper_limit="NA">Overall, 13 (48.1%) patients had experienced progression and 14 (51.9%) were censored, as they were alive and lacked PD assessments or documentation at the time of study termination</measurement>
                    <measurement group_id="O2" value="4.80" lower_limit="2.79" upper_limit="NA">Overall, 13 (48.1%) patients had experienced progression and 14 (51.9%) were censored, as they were alive and lacked PD assessments or documentation at the time of study termination</measurement>
                    <measurement group_id="O3" value="5.78" lower_limit="3.06" upper_limit="NA">Overall, 13 (48.1%) patients had experienced progression and 14 (51.9%) were censored, as they were alive and lacked PD assessments or documentation at the time of study termination</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>TTNT</title>
        <description>To assess time to next treatment (TTNT)</description>
        <time_frame>From randomization to the date of next anti-myeloma treatment. Maximum treatment durations for Arm A and Arm B were 68.4 and 59.0 weeks, respectively.</time_frame>
        <population>Full Analysis set: 14 participants randomized to Arm A and 13 participants randomized to Arm B.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm A</title>
            <description>Melflufen 40 mg iv Day 1 of each 28 day cycle. Dexamethasone 40 mg po Day 1,8, 15 and 22 of each 28 day cycle, if &gt; 75 years of age 20 mg. Cycle 1 will be administered via a Peripheral Venous Catheter (PVC) and cycle 2 and onwards melflufen will be administered via a Central Venous Catheter (CVC).&#xD;
Melphalan: Peripheral versus central administration&#xD;
Dexamethasone: Oral tablets</description>
          </group>
          <group group_id="O2">
            <title>Arm B</title>
            <description>Melflufen 40 mg iv Day 1 of each 28 day cycle. Dexamethasone 40 mg po Day 1,8, 15 and 22 of each 28 day cycle, if &gt; 75 years of age 20 mg. Cycle 1 will be administered via a Central Venous Catheter (CVC) and cycle 2 will be administered via a Peripheral Venous Catheter (PVC). From cycle 3 and onwards melflufen will be administered via CVC.&#xD;
Melphalan: Peripheral versus central administration&#xD;
Dexamethasone: Oral tablets</description>
          </group>
          <group group_id="O3">
            <title>Overall</title>
            <description>Arm A plus Arm B</description>
          </group>
        </group_list>
        <measure>
          <title>TTNT</title>
          <description>To assess time to next treatment (TTNT)</description>
          <population>Full Analysis set: 14 participants randomized to Arm A and 13 participants randomized to Arm B.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="13"/>
                <count group_id="O3" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="NA" upper_limit="NA">In this study, patients were followed to progression. No patients had a new treatment for MM prior to progression, and as a result TTNT was not calculable.</measurement>
                    <measurement group_id="O2" value="NA" lower_limit="NA" upper_limit="NA">In this study, patients were followed to progression. No patients had a new treatment for MM prior to progression, and as a result TTNT was not calculable.</measurement>
                    <measurement group_id="O3" value="NA" lower_limit="NA" upper_limit="NA">In this study, patients were followed to progression. No patients had a new treatment for MM prior to progression, and as a result TTNT was not calculable.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>PFS</title>
        <description>To assess progression free survival (PFS)</description>
        <time_frame>From initiation of therapy until documented disease progression or initiation of new therapy. Maximum treatment durations for Arm A and Arm B were 68.4 and 59.0 weeks, respectively.</time_frame>
        <population>Full Analysis set: 14 participants randomized to Arm A and 13 participants randomized to Arm B.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm A</title>
            <description>Melflufen 40 mg iv Day 1 of each 28 day cycle. Dexamethasone 40 mg po Day 1,8, 15 and 22 of each 28 day cycle, if &gt; 75 years of age 20 mg. Cycle 1 will be administered via a Peripheral Venous Catheter (PVC) and cycle 2 and onwards melflufen will be administered via a Central Venous Catheter (CVC).&#xD;
Melphalan: Peripheral versus central administration&#xD;
Dexamethasone: Oral tablets</description>
          </group>
          <group group_id="O2">
            <title>Arm B</title>
            <description>Melflufen 40 mg iv Day 1 of each 28 day cycle. Dexamethasone 40 mg po Day 1,8, 15 and 22 of each 28 day cycle, if &gt; 75 years of age 20 mg. Cycle 1 will be administered via a Central Venous Catheter (CVC) and cycle 2 will be administered via a Peripheral Venous Catheter (PVC). From cycle 3 and onwards melflufen will be administered via CVC.&#xD;
Melphalan: Peripheral versus central administration&#xD;
Dexamethasone: Oral tablets</description>
          </group>
          <group group_id="O3">
            <title>Overall</title>
            <description>Arm A plus Arm B</description>
          </group>
        </group_list>
        <measure>
          <title>PFS</title>
          <description>To assess progression free survival (PFS)</description>
          <population>Full Analysis set: 14 participants randomized to Arm A and 13 participants randomized to Arm B.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="13"/>
                <count group_id="O3" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.21" lower_limit="2.73" upper_limit="NA">Overall, 19 (70.4%) patients experienced progression during the study and 8 (29.6%) were censored, due to lack of PD assessments or deaths at the time of study termination.</measurement>
                    <measurement group_id="O2" value="2.89" lower_limit="1.51" upper_limit="4.60"/>
                    <measurement group_id="O3" value="3.73" lower_limit="2.73" upper_limit="5.78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Grade 3/4 Treatment-Emergent Adverse Events (TEAEs)</title>
        <description>To assess safety and general tolerability of melflufen by collecting non-serious Adverse Events (AEs) from the start of study treatment until 30 days after the last dose of any study drug (melflufen or dexamethasone) or initiation of subsequent therapy whichever occurred first. Serious AEs (SAEs) were collected from the time the subject signed the ICF until 30 days after the last dose of any study drug (melflufen or dexamethasone) or initiation of subsequent therapy whichever occurred first.</description>
        <time_frame>Median treatment durations for Arm A and Arm B were 29.14 and 12.14 weeks, respectively. The AE reporting period is estimated to be 30 days longer.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm A: Grade 3/4</title>
            <description>Melflufen 40 mg IV Day 1 of each 28 day cycle. Dexamethasone 40 mg PO Days 1, 8, 15 and 22 of each 28 day cycle; if &gt;75 yr of age 20 mg. Cycle 1will be administered via peripheral venous catheter (PVC) and Cycle 2 onwards melflufen will be administered via a central venous catheter (CVC).&#xD;
Melphalan: PVC vs CVC administration Dexamethasone: oral tablets</description>
          </group>
          <group group_id="O2">
            <title>Arm B: Grade 3/4</title>
            <description>Melflufen 40 mg IV Day 1 of each 28 day cycle. Dexamethasone 40 mg PO Days 1, 8, 15 and 22 of each 28 day cycle; if &gt;75 yr of age 20 mg. Cycle 1 will be administered via central venous catheter (CVC). Cycle 2 will be administered via peripheral venous catheter (PVC). From Cycle 3 and onwards melflufen will be administered via CVC.&#xD;
Melphalan: PVC vs CVC administration Dexamethasone: oral tablets</description>
          </group>
          <group group_id="O3">
            <title>Overall: Grade 3/4</title>
            <description>Arm A plus Arm B</description>
          </group>
        </group_list>
        <measure>
          <title>Grade 3/4 Treatment-Emergent Adverse Events (TEAEs)</title>
          <description>To assess safety and general tolerability of melflufen by collecting non-serious Adverse Events (AEs) from the start of study treatment until 30 days after the last dose of any study drug (melflufen or dexamethasone) or initiation of subsequent therapy whichever occurred first. Serious AEs (SAEs) were collected from the time the subject signed the ICF until 30 days after the last dose of any study drug (melflufen or dexamethasone) or initiation of subsequent therapy whichever occurred first.</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="14"/>
                <count group_id="O2" value="13"/>
                <count group_id="O3" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Blood and lymphatic system disorders</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                    <measurement group_id="O2" value="10"/>
                    <measurement group_id="O3" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Thrombocytopenia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="10"/>
                    <measurement group_id="O3" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Neutropenia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="7"/>
                    <measurement group_id="O3" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Anaemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Leukopenia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lymphopenia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Febrile neutropenia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Infections and infestations</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pneumonia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>COVID-19 pneumonia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sepsis</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>General disorders and administration site conditions</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>General physical health deterioration</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Death</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asthenia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Injury, poisoning and procedural complications</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Femur fracture</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Femoral neck fracture</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Gastrointestinal disorders</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Stomatitis</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Musculoskeletal and connective tissue disorders</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Back pain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Musculoskeletal chest pain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nervous system disorders</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ischaemic stroke</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Vascular disorders</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypertension</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Grade 5 Treatment-Emergent Adverse Events (TEAEs)</title>
        <description>To assess safety and general tolerability of melflufen by collecting serious adverse events (SAEs) from the signing of the ICF until 30 days after the last dose of any study drug (melflufen or dexamethasone) or initiation of subsequent therapy whichever comes first.</description>
        <time_frame>From signing of the ICF until 30 days after the last dose of any study drug or initiation of subsequent therapy, whichever comes first. Median treatment durations for Arms A and B were 29.14 weeks and 12.14 weeks. AE reporting period=30 days longer</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm A: Grade 5</title>
            <description>Melflufen 40 mg IV Day 1 of each 28 day cycle. Dexamethasone 40 mg PO Days 1, 8, 15 and 22 of each 28 day cycle; if &gt;75 yr of age 20 mg. Cycle 1will be administered via peripheral venous catheter (PVC) and Cycle 2 onwards melflufen will be administered via a central venous catheter (CVC).&#xD;
Melphalan: PVC vs CVC administration Dexamethasone: oral tablets</description>
          </group>
          <group group_id="O2">
            <title>Arm B: Grade 5</title>
            <description>Melflufen 40 mg IV Day 1 of each 28 day cycle. Dexamethasone 40 mg PO Days 1, 8, 15 and 22 of each 28 day cycle; if &gt;75 yr of age 20 mg. Cycle 1 will be administered via central venous catheter (CVC). Cycle 2 will be administered via peripheral venous catheter (PVC). From Cycle 3 and onwards melflufen will be administered via CVC.&#xD;
Melphalan: PVC vs CVC administration Dexamethasone: oral tablets</description>
          </group>
          <group group_id="O3">
            <title>Overall: Grade 5</title>
            <description>Arm A plus Arm B</description>
          </group>
        </group_list>
        <measure>
          <title>Grade 5 Treatment-Emergent Adverse Events (TEAEs)</title>
          <description>To assess safety and general tolerability of melflufen by collecting serious adverse events (SAEs) from the signing of the ICF until 30 days after the last dose of any study drug (melflufen or dexamethasone) or initiation of subsequent therapy whichever comes first.</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="14"/>
                <count group_id="O2" value="13"/>
                <count group_id="O3" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Infections and infestations</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pneumonia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>COVID-19 pneumonia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>General disorders and administration site conditions</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>General physical health deterioration</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Death</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Gastrointestinal disorders</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ileus</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>SAEs were collected from signing of the ICF until 30 days after last dose of study treatment or initiation of subsequent therapy, whichever occurred first. Non-serious AEs were collected from the start of study treatment until 30 days after the last dose of any study drug or initiation of subsequent therapy, whichever occurred first. Median treatment durations for Arm A and Arm B were 29.14 weeks and 12.14 weeks, respectively. The AE reporting period is estimated to be 30 days longer.</time_frame>
      <desc>Adverse events cannot be compared for Arm A versus Arm B. Because of the crossover design of the study, all patients had a different route of administration in Cycle 2 than Cycle 1, and later AEs could be due to a cumulative effect of multiple treatment cycles. Thus, AEs occurring in Cycle 2 and beyond cannot be attributed to only 1 route of administration.</desc>
      <group_list>
        <group group_id="E1">
          <title>Arm A</title>
          <description>Melflufen 40 mg iv Day 1 of each 28-day cycle. Dexamethasone 40 mg po Days 1,8,15 and 22 of each 28-day cycle (20 mg for patients 75 years or older). Cycle 1 administered via a PVC and Cycle 2 and onwards melflufen administered via a CVC.&#xD;
Melflufen: Peripheral versus central administration&#xD;
Dexamethasone: Oral tablets</description>
        </group>
        <group group_id="E2">
          <title>Arm B</title>
          <description>Melflufen 40 mg iv Day 1 of each 28-day cycle. Dexamethasone 40 mg po Days 1,8,15 and 22 of each 28-day cycle (20 mg for patients 75 years or older). Cycle 1 administered via a CVC and Cycle 2 administered via a PVC. From Cycle 3 and onwards melflufen administered via CVC.&#xD;
Melflufen: Peripheral versus central administration&#xD;
Dexamethasone: Oral tablets</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA version 24.0</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="1" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Ileus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Death</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>General physical health deterioration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Asymptomatic COVID-19</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>COVID-19 pneumonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="14"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Femoral neck fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Femur fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Ischaemic stroke</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA version 24.0</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="13" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="16" subjects_affected="9" subjects_at_risk="14"/>
                <counts group_id="E2" events="12" subjects_affected="7" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" events="7" subjects_affected="2" subjects_at_risk="14"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Lymphopenia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" events="36" subjects_affected="9" subjects_at_risk="14"/>
                <counts group_id="E2" events="33" subjects_affected="9" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" events="34" subjects_affected="10" subjects_at_risk="14"/>
                <counts group_id="E2" events="23" subjects_affected="10" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal discomfort</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>General physical health deterioration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="14"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>COVID-19</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="14"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Rhinitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Femur fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Body temperature increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>C-reactive protein increased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="14"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>SARS-CoV-2 test positive</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="14"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Type 2 diabetes mellitus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="14"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="14"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Musculoskeletal chest pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Aphasia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Cognitive disorder</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Renal impairment</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Rhinorrhoea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="14"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Vascular pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT 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>VP Chief Operating Officer</name_or_title>
      <organization>Oncopeptides AB</organization>
      <phone>+46 8 615 20 40</phone>
      <email>trials@oncopeptides.com</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/NCT04412707
org study id: OP-109
nct id: NCT04412707
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a randomized, two-period, cross-over Phase 2 study, comparing PK, and assessing
      safety and tolerability and efficacy of peripheral and central intravenous administration of
      melflufen in patients with RRMM. It is an international study, enrolling patients in US and
      Europe. The study will enroll patients following at least 2 lines of prior therapy.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Peak Plasma Concentration for Melphalan
time frame: Cycle 1 Day 1 and Cycle 2 Day 1. Samples were collected 5, 10, 15, 20, and 25 minutes after the start of the infusion; immediately before the end of the infusion; and 5, 10, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.
description: To evaluate and compare the pharmacokinetic (PK) variable Cmax of melphalan after central and peripheral intravenous infusion of melflufen.
measure: Area Under the Plasma Concentration Versus Time Curve AUC(0-t) of Melphalan
time frame: Cycle 1 Day 1 and Cycle 2 Day 1. Samples were collected 5, 10, 15, 20, and 25 minutes after the start of the infusion; immediately before the end of the infusion; and 5, 10, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.
description: To evaluate and compare the pharmacokinetic (PK) variable AUC(0-t) of melphalan after central and peripheral intravenous infusion of melflufen.
measure: Area Under the Plasma Concentration Versus Time Curve AUC(0-inf) of Melphalan
time frame: Cycle 1 Day 1 and Cycle 2 Day 1. Samples were collected 5, 10, 15, 20, and 25 minutes after the start of the infusion; immediately before the end of the infusion; and 5, 10, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.
description: To evaluate and compare the pharmacokinetic (PK) variable AUC(0-inf) of melphalan after central and peripheral intravenous infusion of melflufen
measure: Number of Participants With Local Reactions Including Phlebitis at Infusion Site After Peripheral Intravenous Administration
time frame: 15 minutes and 4 hours after peripheral intravenous administration, pre- and post-infusion on Day 1 and Day 8
description: Assessment of the local tolerability of peripheral intravenous administration of melflufen using the Visual Infusion Phlebitis (VIP) scale. The VIP scale provides a score from 0 to 5, noting an ascending order of severity of inflammation. A score of 0 is the lowest possible score, meaning no inflammation detected, and 5 is the highest score, indicating the most severe reaction.
measure: Peak Plasma Concentration for Melflufen and Desethyl-melflufen
time frame: Cycle 1 Day 1 and Cycle 2 Day 1 - 13 PK samples during and post infusion (28 days cycle)
description: To evaluate and compare the pharmacokinetic (PK) variable Cmax of melflufen and desethyl-melflufen after central and peripheral intravenous infusion of melflufen.
measure: Area Under the Plasma Concentration Versus Time Curve AUC(0-t) of Melflufen and Desethyl-melflufen
time frame: Cycle 1 Day 1 and Cycle 2 Day 1 - 13 PK samples during and post infusion (28 days cycle)
description: To evaluate and compare the pharmacokinetic (PK) variable AUC(0-t) of melflufen and desethyl-melflufen after central and peripheral intravenous infusion of melflufen
measure: Area Under the Plasma Concentration Versus Time Curve AUC(0-inf) of Melflufen and Desethyl-melflufen
time frame: Cycle 1 Day 1 and Cycle 2 Day 1 - 13 PK samples during and post infusion (28 days cycle)
description: To evaluate and compare the pharmacokinetic (PK) variable AUC(0-inf) of melflufen and desethyl-melflufen after central and peripheral intravenous infusion of melflufen
measure: Elimination Half-life (t1/2) of Melflufen, Melphalan and Desethyl-melflufen
time frame: Cycle 1 Day 1 and Cycle 2 Day 1 - 13 measurements during and post infusion (28 days cycle)
description: To evaluate elimination half-life (t½) for melflufen, melphalan and desethyl-melflufen after central and peripheral intravenous infusion of melflufen.
measure: Frequency of Treatment-Emergent Adverse Events (TEAEs) by MedDRA SOC and PT
time frame: Median treatment durations for Arm A and Arm B were 29.14 weeks and 12.14 weeks, respectively. The AE reporting period is estimated to be 30 days longer.
description: To assess safety and general tolerability of melflufen by collecting non-serious Adverse Events (AEs) from the start of study treatment until 30 days after the last dose of any study drug (melflufen or dexamethasone) or initiation of subsequent therapy whichever occurred first. Serious AEs (SAEs) were collected from the time the subject signed the ICF until 30 days after the last dose of any study drug (melflufen or dexamethasone) or initiation of subsequent therapy whichever occurred first.
measure: Best Response (Stringent Complete Response (sCR), Complete Response (CR), Very Good Partial Response (VGPR), Partial Response (PR), Minimal Response (MR), Stable Disease (SD) or Progressive Disease (PD)
time frame: From initiation of therapy until disease progression. Median treatment durations for Arm A and Arm B were 29.14 weeks and 12.14 weeks, respectively.
description: To assess best response during the study with the criteria established by the International Myeloma Working Group Uniform Response Criteria (IMWG-URC) for sCR, CR, VGPR, PR, SD and PD
measure: ORR
time frame: From initiation of therapy until disease progression. Maximum treatment durations for Arm A and Arm B were 68.4 and 59.0 weeks, respectively.
description: To assess overall response rate (ORR), including CR/sCR, VGPR and PR, during the study with the criteria established by the IMWG-URC.
measure: CBR
time frame: To be assessed at the end of study drug treatment. Maximum treatment durations for Arm A and Arm B were 68.4 and 59.0 weeks, respectively.
description: To assess clinical benefit rate (CBR), i.e., proportion of patients that achieve a confirmed minimal response or better (sCR, CR, VGPR, PR and MR), during the study with the criteria established by the IMWG-URC.
measure: DOR
time frame: From confirmed response until disease progression. Maximum treatment durations for Arm A and Arm B were 68.4 and 59.0 weeks, respectively.
description: To assess duration of response (DOR): the time in months from the first evidence of confirmed assessment of sCR, CR, VGPR, or PR to first confirmed disease progression according to the criteria established by the IMWG-URC or to death due to any cause. DOR is defined only for patients with a confirmed PR or better.
measure: DOCB
time frame: From first evidence of confirmed assessment of sCR, CR, VGPR, PR or MR to first confirmed disease progression, or to death due to any cause. Maximum treatment durations for Arm A and Arm B were 68.4 and 59.0 weeks, respectively.
description: To assess duration of clinical benefit (DOCB) in patients with stringent complete response (sCR), complete response (CR), very good partial response (VGPR), PR, or MR during the study with the criteria established by the IMWG-URC.
measure: TTR
time frame: From initiation of therapy until documented disease response. Maximum treatment durations for Arm A and Arm B were 68.4 and 59.0 weeks, respectively.
description: To assess time to response (TTR) in patients with PR or better during the study with the criteria established by the UMWG-URC.
measure: TTP
time frame: From date of randomization until documented disease progression. Maximum treatment durations for Arm A and Arm B were 68.4 and 59.0 weeks, respectively.
description: To assess time to progression (TTP) during the study with the criteria established by the IMWG-URC.
measure: TTNT
time frame: From randomization to the date of next anti-myeloma treatment. Maximum treatment durations for Arm A and Arm B were 68.4 and 59.0 weeks, respectively.
description: To assess time to next treatment (TTNT)
measure: PFS
time frame: From initiation of therapy until documented disease progression or initiation of new therapy. Maximum treatment durations for Arm A and Arm B were 68.4 and 59.0 weeks, respectively.
description: To assess progression free survival (PFS)
measure: Grade 3/4 Treatment-Emergent Adverse Events (TEAEs)
time frame: Median treatment durations for Arm A and Arm B were 29.14 and 12.14 weeks, respectively. The AE reporting period is estimated to be 30 days longer.
description: To assess safety and general tolerability of melflufen by collecting non-serious Adverse Events (AEs) from the start of study treatment until 30 days after the last dose of any study drug (melflufen or dexamethasone) or initiation of subsequent therapy whichever occurred first. Serious AEs (SAEs) were collected from the time the subject signed the ICF until 30 days after the last dose of any study drug (melflufen or dexamethasone) or initiation of subsequent therapy whichever occurred first.
measure: Grade 5 Treatment-Emergent Adverse Events (TEAEs)
time frame: From signing of the ICF until 30 days after the last dose of any study drug or initiation of subsequent therapy, whichever comes first. Median treatment durations for Arms A and B were 29.14 weeks and 12.14 weeks. AE reporting period=30 days longer
description: To assess safety and general tolerability of melflufen by collecting serious adverse events (SAEs) from the signing of the ICF until 30 days after the last dose of any study drug (melflufen or dexamethasone) or initiation of subsequent therapy whichever comes first.
arm group label: Arm A
arm group type: Active Comparator
description: Melflufen 40 mg iv Day 1 of each 28 day cycle. Dexamethasone 40 mg po Day 1,8, 15 and 22 of each 28 day cycle, if > 75 years of age 20 mg. Cycle 1 will be administered via a Peripheral Venous Catheter (PVC) and cycle 2 and onwards melflufen will be administered via a Central Venous Catheter (CVC).
arm group label: Arm B
arm group type: Active Comparator
description: Melflufen 40 mg iv Day 1 of each 28 day cycle. Dexamethasone 40 mg po Day 1,8, 15 and 22 of each 28 day cycle, if > 75 years of age 20 mg. Cycle 1 will be administered via a Central Venous Catheter (CVC) and cycle 2 will be administered via a Peripheral Venous Catheter (PVC). From cycle 3 and onwards melflufen will be administered via CVC.
intervention type: Drug
intervention name: Melphalan
description: Peripheral versus central administration
arm group label: Arm A
arm group label: Arm B
other name: melflufen flufenamide
intervention type: Drug
intervention name: Dexamethasone
description: Oral tablets
arm group label: Arm A
arm group label: Arm B
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Bulgaria
country: Czechia
country: Hungary
country: Ukraine
country: United States
responsible party type: Sponsor
mesh term: Dexamethasone
mesh term: Melphalan
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 