<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/NCT03015922</url>
  </required_header>
  <id_info>
    <org_study_id>HM16/118</org_study_id>
    <nct_id>NCT03015922</nct_id>
  </id_info>
  <brief_title>Viral Immunotherapy in Relapsed/Refractory Multiple Myeloma</brief_title>
  <acronym>MUKeleven</acronym>
  <official_title>VIRel: Viral Immunotherapy in Relapsed/Refractory Multiple Myeloma - A Phase I Study to Assess the Safety and Tolerability of REOLYSIN® (Pelareorep) in Combination With Lenalidomide or Pomalidomide</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Leeds</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Myeloma UK</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Oncolytics Biotech</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Celgene Corporation</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Leeds</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will recruit patients currently receiving either lenalidomide or pomalidomide&#xD;
      whose disease is relapsing. This is a dose escalation study and the aim is to determine the&#xD;
      maximum tolerated dose (MTD) of REOLYSIN® that can be given in combination with lenalidomide&#xD;
      or pomalidomide. The study will also investigate the safety, side effects and effectiveness&#xD;
      of this treatment combination. Pomalidomide and lenalidomide will be evaluated separately as&#xD;
      two separate groups.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">June 5, 2017</start_date>
  <completion_date type="Anticipated">October 1, 2021</completion_date>
  <primary_completion_date type="Anticipated">September 1, 2021</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Dose-limiting toxicities</measure>
    <time_frame>After cycle 1 (28 days) of treatment. Assessed in real-time for each patient to inform dose escalation decisions.</time_frame>
    <description>Dose-limiting toxicities (DLTs), within the first cycle (until cycle 2, day 1), in order to establish the Maximum Tolerated Dose (MTD) of REOLYSIN® in combination with lenalidomide or pomalidomide, in two separate groups of participants.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety profile of REOLYSIN® and lenalidomide</measure>
    <time_frame>Until 28 days after the last dose of trial treatment for each patient. Assessed up to 27 months.</time_frame>
    <description>Safety will be reported based on the occurrence of SAEs, SARs and SUSARs.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety profile of REOLYSIN® and pomalidomide</measure>
    <time_frame>Until 28 days after the last dose of trial treatment for each patient. Assessed up to 27 months.</time_frame>
    <description>Safety will be reported based on the occurrence of SAEs, SARs and SUSARs.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Toxicity profile of REOLYSIN® and lenalidomide</measure>
    <time_frame>Until 28 days after the last dose of trial treatment fior each patient. Assessed up to 27 months.</time_frame>
    <description>Toxicity will be reported based on adverse events, as graded by CTCAE V4.0, and determined by routine clinical assessments at each centre.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Toxicity profile of REOLYSIN® and pomalidomide</measure>
    <time_frame>Until 28 days after the last dose of trial treatment fior each patient. Assessed up to 27 months.</time_frame>
    <description>Toxicity will be reported based on adverse events, as graded by CTCAE V4.0, and determined by routine clinical assessments at each centre.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response rate (stable disease or better) after 6 cycles of therapy</measure>
    <time_frame>Data will be collected from each patient after they have received 6 cycles of therapy, if this stage is reached. 6 cycles are expected to take 24 weeks to complete.</time_frame>
    <description>Measured only in patients treated at the maximum tolerated dose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum response within 6 cycles of therapy</measure>
    <time_frame>Assessed for each patient after they have received 6 cycles of treatment. 6 cycles are expected to take 24 weeks to complete.</time_frame>
    <description>Measured only in patients treated at the maximum tolerated dose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum response overall</measure>
    <time_frame>Assessed for each patient after they have completed treatment on the trial. Assessed up to 27 months.</time_frame>
    <description>Measured only in patients treated at the maximum tolerated dose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to maximum response</measure>
    <time_frame>Assessed for each patient after they have completed treatment on the trial. Assessed up to 27 months.</time_frame>
    <description>Measured only in patients treated at the maximum tolerated dose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival</measure>
    <time_frame>Calculated for each patient from the date of registration up to first documented evidence of disease progression or death. Assessed up to 27 months.</time_frame>
    <description>Measured only in patients treated at the maximum tolerated dose. Participants who have not progressed at the time of analysis will be censored at the last date they were known to be alive and progression free.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>Calculated for each patient from the date of registration to death. Assessed up to 27 months.</time_frame>
    <description>Measured only in patients treated at the maximum tolerated dose. Participants who have not died at the time of analysis will be censored at the last date they were known to be alive.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Immune response biomarker profile of REOLYSIN and lenalidomide administered in combination</measure>
    <time_frame>This will be assessed based on samples taken throughout each patient's time on the trial. Assessed up to 27 months.</time_frame>
    <description>Biomarker profiling of the combination treatment</description>
  </other_outcome>
  <other_outcome>
    <measure>Immune response biomarker profile of REOLYSIN® and pomalidomide administered in combination</measure>
    <time_frame>This will be assessed based on samples taken throughout each patient's time on the trial. Assessed up to 27 months.</time_frame>
    <description>Biomarker profiling of the combination treatment</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">4</enrollment>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>Lenalidomide or pomalidomide, plus REOLYSIN</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Lenalidomide capsules, oral, maximum 10mg daily on days 1-21 of 28-day cycles. OR Pomalidomide capsules, oral, maximum 1mg daily on days 1-21 of 28-day cycles.&#xD;
Plus (all patients):&#xD;
REOLYSIN® , intravenous infusion, maximum 3x10^10 TCID50 on days 1, 8, 15 and 22 of 28-day cycles.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lenalidomide or Pomalidomide</intervention_name>
    <description>Patients will received either lenalidomide or pomalidomide, depending on which drug they were receiving prior to the trial (they will receive the same as before).</description>
    <arm_group_label>Lenalidomide or pomalidomide, plus REOLYSIN</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>REOLYSIN</intervention_name>
    <description>Patients will receive Reolysin alongside either lenalidomide or pomalidomide</description>
    <arm_group_label>Lenalidomide or pomalidomide, plus REOLYSIN</arm_group_label>
    <other_name>Pelareorep</other_name>
    <other_name>Reovirus</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosed with symptomatic multiple myeloma (according to IMWG 2014 criteria)&#xD;
&#xD;
          -  Evaluable disease by modified IMWG criteria (i.e. by abnormal serum M protein, urinary&#xD;
             M protein or serum free light chain assays)&#xD;
&#xD;
          -  Currently receiving either lenalidomide or pomalidomide therapy, alone or in&#xD;
             combination with other myeloma therapy, with evidence of serological or clinical&#xD;
             disease progression as defined by IMWG criteria (2011)&#xD;
&#xD;
          -  Life expectancy of ≥ 3 months&#xD;
&#xD;
          -  ECOG performance status of ≤2&#xD;
&#xD;
          -  Required laboratory values within 14 days prior to dose allocation:&#xD;
&#xD;
          -  Absolute neutrophil count ≥ 1.0 x10^9 /L. (growth factor support is not permitted)&#xD;
&#xD;
          -  Platelet count ≥ 70 x 10^9/L. (platelet support is not permitted; platelets &lt; 70 but ≥&#xD;
             25 acceptable if bone marrow is &gt; 50% infiltrated by MM)&#xD;
&#xD;
          -  Haemoglobin ≥ 8 g/dL. Blood support is permitted&#xD;
&#xD;
          -  Serum bilirubin ≤ 2 x upper limit of normal (ULN)&#xD;
&#xD;
          -  ALT or AST ≤ 2.5 x ULN&#xD;
&#xD;
          -  Serum creatinine ≤ 2 x ULN&#xD;
&#xD;
          -  Corrected calcium ≤ 2.8 mmol/l&#xD;
&#xD;
          -  Negative HIV and viral (B and C) hepatitis test result within 14 days prior to dose&#xD;
             allocation&#xD;
&#xD;
          -  Able to give informed consent and willing to follow trial protocol&#xD;
&#xD;
          -  Aged 18 years or over&#xD;
&#xD;
          -  All participants must agree to follow the Celgene Pregnancy Prevention Programme (PPP)&#xD;
             and participate in the counselling associated with this:&#xD;
&#xD;
          -  Females of childbearing potential (FCBP) must agree to utilise two reliable forms of&#xD;
             contraception simultaneously or practice complete abstinence for at least for 28 days&#xD;
             prior to starting trial treatment, during the trial and for at least 28 days after&#xD;
             trial treatment discontinuation, and even in case of dose interruption, and must agree&#xD;
             to Celgene PPP pregnancy testing during this timeframe&#xD;
&#xD;
          -  Females must agree to abstain from breastfeeding during trial participation and 28&#xD;
             days after trial drug discontinuation&#xD;
&#xD;
          -  Males must agree to use a latex condom during any sexual contact with FCBP (or must&#xD;
             practice complete abstinence) during the trial, including during dose interruptions&#xD;
             and for 28 days following discontinuation from this trial even if he has undergone a&#xD;
             successful vasectomy&#xD;
&#xD;
          -  Males must also agree to refrain from donating semen or sperm while on pomalidomide&#xD;
             including during any dose interruptions and for 28 days after discontinuation from&#xD;
             this trial&#xD;
&#xD;
          -  All participants must agree to refrain from donating blood while on trial drug&#xD;
             including during dose interruptions and for 28 days after discontinuation from this&#xD;
             trial&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Non-secretory multiple myeloma&#xD;
&#xD;
          -  Pregnant (positive pregnancy test) in line with the Celgene Pregnancy Prevention&#xD;
             Programme or breast feeding&#xD;
&#xD;
          -  Previous anti-tumour therapies including experimental agents, other than lenalidomide&#xD;
             or pomalidomide, within 28 days of the start of protocol treatment. Steroid therapy is&#xD;
             permitted, but must be stopped 48 hours prior to cycle 1 day 1&#xD;
&#xD;
          -  Concurrent or previous malignancies (&lt;12 months post end of treatment) at other sites,&#xD;
             with the exception of appropriately treated localised epithelial skin or cervical&#xD;
             cancer, or incidental histologic findings of prostate cancer (TNM stage T1a or 1b).&#xD;
             Participants with histories (≥12 months) of other tumours, in remission and not&#xD;
             currently on therapy, may be entered&#xD;
&#xD;
          -  System corticosteroid therapy for comorbidities (i.e. medical conditions other than&#xD;
             multiple myeloma) that cannot be stopped for the duration of the trial. Topical&#xD;
             corticosteroid therapy is not an exclusion criterion.&#xD;
&#xD;
          -  Any history of known hypersensitivity to any of the trial medications or excipients&#xD;
&#xD;
          -  Active symptomatic fungal, bacterial, and/or viral infection&#xD;
&#xD;
          -  Poorly controlled or serious medical or psychiatric illness that, in the&#xD;
             Investigator's opinion, is likely to interfere with participation and/or compliance in&#xD;
             this clinical trial&#xD;
&#xD;
          -  Patients with significant cardiovascular disease (e.g. history of congestive heart&#xD;
             failure requiring therapy (≥ NYHA Class III), presence of severe valvular heart&#xD;
             disease, presence of an atrial or ventricular arrhythmia requiring treatment,&#xD;
             uncontrolled hypertension, or history of QTc abnormalities)&#xD;
&#xD;
          -  Radiotherapy or major surgery within 4 weeks prior to registration&#xD;
&#xD;
          -  Greater than or equal to grade 2 neuropathy, with or without pain&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gordon Cook</last_name>
    <role>Principal Investigator</role>
    <affiliation>St. James's University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>St James's University Hospital</name>
      <address>
        <city>Leeds</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sheffield Teaching Hospitals NHS Foundation Trust, Northern General Hospital</name>
      <address>
        <city>Sheffield</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>November 16, 2016</study_first_submitted>
  <study_first_submitted_qc>January 6, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 10, 2017</study_first_posted>
  <last_update_submitted>January 21, 2020</last_update_submitted>
  <last_update_submitted_qc>January 21, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 22, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The Leeds Teaching Hospitals NHS Trust</investigator_affiliation>
    <investigator_full_name>Gordon Cook</investigator_full_name>
    <investigator_title>Consultant Haematologist</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Myeloma</mesh_term>
    <mesh_term>Neoplasms, Plasma Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lenalidomide</mesh_term>
    <mesh_term>Pomalidomide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03015922
org study id: HM16/118
nct id: NCT03015922
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study will recruit patients currently receiving either lenalidomide or pomalidomide
      whose disease is relapsing. This is a dose escalation study and the aim is to determine the
      maximum tolerated dose (MTD) of REOLYSIN® that can be given in combination with lenalidomide
      or pomalidomide. The study will also investigate the safety, side effects and effectiveness
      of this treatment combination. Pomalidomide and lenalidomide will be evaluated separately as
      two separate groups.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Dose-limiting toxicities
time frame: After cycle 1 (28 days) of treatment. Assessed in real-time for each patient to inform dose escalation decisions.
description: Dose-limiting toxicities (DLTs), within the first cycle (until cycle 2, day 1), in order to establish the Maximum Tolerated Dose (MTD) of REOLYSIN® in combination with lenalidomide or pomalidomide, in two separate groups of participants.
measure: Safety profile of REOLYSIN® and lenalidomide
time frame: Until 28 days after the last dose of trial treatment for each patient. Assessed up to 27 months.
description: Safety will be reported based on the occurrence of SAEs, SARs and SUSARs.
measure: Safety profile of REOLYSIN® and pomalidomide
time frame: Until 28 days after the last dose of trial treatment for each patient. Assessed up to 27 months.
description: Safety will be reported based on the occurrence of SAEs, SARs and SUSARs.
measure: Toxicity profile of REOLYSIN® and lenalidomide
time frame: Until 28 days after the last dose of trial treatment fior each patient. Assessed up to 27 months.
description: Toxicity will be reported based on adverse events, as graded by CTCAE V4.0, and determined by routine clinical assessments at each centre.
measure: Toxicity profile of REOLYSIN® and pomalidomide
time frame: Until 28 days after the last dose of trial treatment fior each patient. Assessed up to 27 months.
description: Toxicity will be reported based on adverse events, as graded by CTCAE V4.0, and determined by routine clinical assessments at each centre.
measure: Response rate (stable disease or better) after 6 cycles of therapy
time frame: Data will be collected from each patient after they have received 6 cycles of therapy, if this stage is reached. 6 cycles are expected to take 24 weeks to complete.
description: Measured only in patients treated at the maximum tolerated dose
measure: Maximum response within 6 cycles of therapy
time frame: Assessed for each patient after they have received 6 cycles of treatment. 6 cycles are expected to take 24 weeks to complete.
description: Measured only in patients treated at the maximum tolerated dose
measure: Maximum response overall
time frame: Assessed for each patient after they have completed treatment on the trial. Assessed up to 27 months.
description: Measured only in patients treated at the maximum tolerated dose
measure: Time to maximum response
time frame: Assessed for each patient after they have completed treatment on the trial. Assessed up to 27 months.
description: Measured only in patients treated at the maximum tolerated dose
measure: Progression-free survival
time frame: Calculated for each patient from the date of registration up to first documented evidence of disease progression or death. Assessed up to 27 months.
description: Measured only in patients treated at the maximum tolerated dose. Participants who have not progressed at the time of analysis will be censored at the last date they were known to be alive and progression free.
measure: Overall survival
time frame: Calculated for each patient from the date of registration to death. Assessed up to 27 months.
description: Measured only in patients treated at the maximum tolerated dose. Participants who have not died at the time of analysis will be censored at the last date they were known to be alive.
measure: Immune response biomarker profile of REOLYSIN and lenalidomide administered in combination
time frame: This will be assessed based on samples taken throughout each patient's time on the trial. Assessed up to 27 months.
description: Biomarker profiling of the combination treatment
measure: Immune response biomarker profile of REOLYSIN® and pomalidomide administered in combination
time frame: This will be assessed based on samples taken throughout each patient's time on the trial. Assessed up to 27 months.
description: Biomarker profiling of the combination treatment
arm group label: Lenalidomide or pomalidomide, plus REOLYSIN
arm group type: Experimental
description: Lenalidomide capsules, oral, maximum 10mg daily on days 1-21 of 28-day cycles. OR Pomalidomide capsules, oral, maximum 1mg daily on days 1-21 of 28-day cycles.
Plus (all patients):
REOLYSIN® , intravenous infusion, maximum 3x10^10 TCID50 on days 1, 8, 15 and 22 of 28-day cycles.
intervention type: Drug
intervention name: Lenalidomide or Pomalidomide
description: Patients will received either lenalidomide or pomalidomide, depending on which drug they were receiving prior to the trial (they will receive the same as before).
arm group label: Lenalidomide or pomalidomide, plus REOLYSIN
intervention type: Biological
intervention name: REOLYSIN
description: Patients will receive Reolysin alongside either lenalidomide or pomalidomide
arm group label: Lenalidomide or pomalidomide, plus REOLYSIN
other name: Pelareorep
other name: Reovirus
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Gordon Cook
role: Principal Investigator
affiliation: St. James's University Hospital
facility: 
facility: 
country: United Kingdom
responsible party type: Principal Investigator
investigator affiliation: The Leeds Teaching Hospitals NHS Trust
investigator full name: Gordon Cook
investigator title: Consultant Haematologist
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Lenalidomide
mesh term: Pomalidomide
sharing ipd: No