<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/NCT02219178</url>
  </required_header>
  <id_info>
    <org_study_id>CTRIAL-IE (ICORG) 13-17</org_study_id>
    <secondary_id>2013-005008-32</secondary_id>
    <nct_id>NCT02219178</nct_id>
  </id_info>
  <brief_title>Study of the Efficacy and Safety of RsqVD Combination Therapy for Patients With Newly Diagnosed Multiple Myeloma</brief_title>
  <official_title>A Phase II Study of the Efficacy and Safety of Lenalidomide, Subcutaneous Bortezomib, and Dexamethasone Combination Therapy for Patients With Newly Diagnosed Multiple Myeloma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cancer Trials Ireland</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Cancer Trials Ireland</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study aims to evaluate the overall response rate after 4 cycles and the best response to&#xD;
      induction therapy with combination of lenalidomide, subcutaneous bortezomib, and&#xD;
      dexamethasone (RsqVD) in patients with newly diagnosed multiple myeloma.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>November 2014</start_date>
  <completion_date type="Actual">April 2020</completion_date>
  <primary_completion_date type="Actual">October 31, 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>To evaluate the overall response rate (ORR) after 4 induction cycles</measure>
    <time_frame>After 4 cycles (84 days)</time_frame>
    <description>To evaluate the overall response rate (ORR) after 4 induction cycles and the best response to induction therapy with the combination of lenalidomide, subcutaneous (SQ) bortezomib, and dexamethasone (RsqVD) in patients with newly diagnosed multiple myeloma.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>a) To evaluate the rate and severity of Peripheral Neuropathy (PN) of SQ bortezomib in combination with lenalidomide, and dexamethasone after the 4th and after the final cycle of induction therapy.</measure>
    <time_frame>After 4 cycles (84 days)</time_frame>
    <description>Evaluate the rate and severity of Peripheral Neuropathy of SQ bortezomib in combination with lenalidomide, and dexamethasone after the 4th and after the final cycle of induction therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression of disease</measure>
    <time_frame>Duration of the study, expected to be approximately 3 years</time_frame>
    <description>Evaluate the time to progression</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>Duration of the study, expected to be approximately 3 years</time_frame>
    <description>Evaluate progression free survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response</measure>
    <time_frame>Duration of the study, expected to be approximately 3 years</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">42</enrollment>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>RsqVD</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral lenalidomide 25mg days 1 - 14 of 21 day schedule Subcutaneous bortezomib 1.3mg/m2 days 1, 4, 8, 11 of 21 day schedule Oral dexamethasone 20mg on days 1, 2, 4, 5, 8, 9, 11, 12 of 21 day schedule</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>lenalidomide</intervention_name>
    <description>25mg days 1 - 14 of 21 day schedule</description>
    <arm_group_label>RsqVD</arm_group_label>
    <other_name>Revlimid</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Subcutaneous bortezomib</intervention_name>
    <description>1.3mg/m2 days 1, 4, 8, 11 of 21 day schedule</description>
    <arm_group_label>RsqVD</arm_group_label>
    <other_name>Velcade</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexamethasone</intervention_name>
    <description>20mg on days 1, 2, 4, 5, 8, 9, 11, 12 of 21 day schedule</description>
    <arm_group_label>RsqVD</arm_group_label>
    <other_name>Decadron</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Participants must have a diagnosis of symptomatic MM, according to International&#xD;
             Myeloma Foundation 2003 Diagnostic Criteria:&#xD;
&#xD;
               -  Clonal plasma cells &gt; 10% on bone marrow biopsy&#xD;
&#xD;
               -  A monoclonal protein (paraprotein) in either serum or urine ( except in the cases&#xD;
                  of non-secretory myeloma).&#xD;
&#xD;
             If no monoclonal protein is detected (non-secretory disease), then ≥ 30% monoclonal&#xD;
             bone marrow plasma cells and/or a biopsy-proven plasmacytoma required.&#xD;
&#xD;
               -  Evidence of end-organ damage felt related to the plasma cell disorder related&#xD;
                  organ or tissue impairment (ROTI), commonly referred to by the acronym 'CRAB':&#xD;
&#xD;
                    -  Hypercalcaemia: serum calcium (corrected for albumin) &gt;&#xD;
                       10.5mg/sL/&gt;2.65mmol/L or upper limit of normal&#xD;
&#xD;
                    -  Renal insufficiency defined as serum creatinine &gt; 2mg/sL/177μmol/L&#xD;
&#xD;
                    -  Anaemia: Normochromic, normocytic with a haemoglobin value &gt; 2g/dL below the&#xD;
                       lower limit of normal or a haemoglobin &lt; 10g/dL&#xD;
&#xD;
                    -  Bone lesions (lytic lesions, severe osteopenia or pathologic fractures) as&#xD;
                       shown by CT scan and/or skeletal survey&#xD;
&#xD;
          2. Patient has received no prior treatment with any systemic therapy for the treatment of&#xD;
             multiple myeloma.&#xD;
&#xD;
               -  Prior treatment of hypercalcaemia or spinal cord compression with corticosteroids&#xD;
                  does not disqualify the patient (the dose should not exceed the equivalent of 160&#xD;
                  mg of dexamethasone in a 2 week period)&#xD;
&#xD;
               -  Bisphosphonates are permitted&#xD;
&#xD;
               -  Patients treated with local radiotherapy with or without concomitant exposure to&#xD;
                  steroids, for pain control or management of cord/nerve root compression, are&#xD;
                  eligible. Two weeks must have lapsed since last date of radiotherapy, which is&#xD;
                  recommended to be a limited field. Patients who require concurrent radiotherapy&#xD;
                  should have entry to the protocol deferred until the radiotherapy is completed&#xD;
                  and 2 weeks have passed since the last date of therapy.&#xD;
&#xD;
          3. Voluntary written informed consent before performance of any study-related procedure&#xD;
             not part of normal medical care, with the understanding that consent may be withdrawn&#xD;
             by the subject at any time without prejudice to future medical care&#xD;
&#xD;
          4. Age ≥ 18 years at the time of signing Informed Consent&#xD;
&#xD;
          5. Females of reproductive potential must adhere to the scheduled pregnancy testing as&#xD;
             required in the Lenalidomide Pregnancy Prevention Risk Management Plan. Females of&#xD;
             childbearing potential (FCBP) must have a negative serum or urine pregnancy test with&#xD;
             a sensitivity of at least 50 mlU/mL 10 to14 days prior to therapy and repeated again&#xD;
             within 24 hours prior to prescribing lenalidomide for Cycle 1 (prescriptions must be&#xD;
             filled within 7 days as required by Lenalidomide Pregnancy Prevention Risk Management&#xD;
             Plan) and must either commit to complete abstinence from heterosexual contact or begin&#xD;
             TWO acceptable methods of birth control, one highly effective method and one&#xD;
             additional effective (barrier) method, AT THE SAME TIME, at least 28 days before she&#xD;
             starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men&#xD;
             must practice complete abstinence or agree to use a condom during sexual contact with&#xD;
             a FCBP even if they have had a successful vasectomy. All study participants must be&#xD;
             registered into the mandatory Lenalidomide Pregnancy Prevention Risk Management Plan,&#xD;
             and be willing and able to comply with the requirements of the Lenalidomide Pregnancy&#xD;
             Prevention Risk Management Plan.*A female of childbearing potential is a sexually&#xD;
             mature female who: 1) has not undergone a hysterectomy (the surgical removal of the&#xD;
             uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or 2) has not&#xD;
             been naturally postmenopausal (amenorrhea following cancer therapy does not rule out&#xD;
             childbearing potential) for at least 24 consecutive months (i.e. has had menses at any&#xD;
             time during the preceding 24 consecutive months)&#xD;
&#xD;
          6. All necessary baseline studies for determining eligibility must be obtained within 21&#xD;
             days prior to enrolment&#xD;
&#xD;
          7. Subject has an ECOG performance status of &lt; 2 or Karnofsky performance status of ≥ 60&#xD;
             (Appendix E).&#xD;
&#xD;
          8. Subject must be able to adhere to the study visit schedule and other protocol&#xD;
             requirements.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patient has ≥ Grade 2 peripheral neuropathy on clinical examination within 14 days&#xD;
             before enrolment&#xD;
&#xD;
          2. Renal insufficiency (serum creatinine levels &gt; 2.5 mg/dL/221μmol/L, calculated&#xD;
             creatinine clearance with Cockcroft-Gault formula (see Appendix G) &lt; 45 ml/min)&#xD;
&#xD;
          3. Subjects with evidence of mucosal or internal bleeding and/or platelet refractory&#xD;
             (i.e. unable to maintain a platelet count 50,000 cells/mm3)&#xD;
&#xD;
          4. Subjects with an absolute neutrophil count (ANC) &lt; 1000 cells/mm3. Growth factors may&#xD;
             not be used to meet ANC eligibility criteria&#xD;
&#xD;
          5. Subjects with a haemoglobin &lt; 8.0 g/dL&#xD;
&#xD;
          6. AST (SGOT) and ALT (SGPT) &gt; 2 x ULN, bilirubin levels 1.5 ULN&#xD;
&#xD;
          7. Concomitant therapy medications that include corticosteroids (except as indicated in&#xD;
             inclusion criteria)&#xD;
&#xD;
          8. Myocardial infarction within 6 months prior to enrolment or has New York Heart&#xD;
             Association (NYHA) Class III or IV heart failure (Appendix G), uncontrolled angina,&#xD;
             severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute&#xD;
             ischemia or active conduction system abnormalities&#xD;
&#xD;
          9. Clinically relevant active infection requiring treatment (antibiotics, antivirals,&#xD;
             antifungals)&#xD;
&#xD;
         10. Any serious co-morbid condition, including laboratory abnormalities, that in the&#xD;
             opinion of the Investigator places the subject at unacceptable risk if he/she were to&#xD;
             participate in the study.&#xD;
&#xD;
         11. Female subject is pregnant or breast-feeding&#xD;
&#xD;
         12. Serious psychiatric illness or addiction likely to interfere with participation in&#xD;
             this clinical study&#xD;
&#xD;
         13. Uncontrolled diabetes mellitus&#xD;
&#xD;
         14. Contraindication to any required concomitant drugs or supportive therapies including&#xD;
             hypersensitivity to all anticoagulation and antiplatelet options or hypersensitivity&#xD;
             to acyclovir or similar anti-viral drug. History of allergic reaction/hypersensitivity&#xD;
             attributed to compounds containing boron, mannitol, polysorbate 80 or sodium citrate&#xD;
             dehydrate&#xD;
&#xD;
         15. POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly,&#xD;
             endocrinopathy, monoclonal protein (M-protein) and skin changes)&#xD;
&#xD;
         16. Known seropositive for or active HIV infection or active hepatitis B or C viral&#xD;
             infection. Patients who are seropositive because of hepatitis B virus vaccine are&#xD;
             eligible&#xD;
&#xD;
         17. Known intolerance to steroid therapy&#xD;
&#xD;
         18. Patient has hypersensitivity to bortezomib, boron, or mannitol&#xD;
&#xD;
         19. Diagnosed or treated for another malignancy within 2 years of enrolment, with the&#xD;
             exception of complete resection of basal cell carcinoma or squamous cell carcinoma of&#xD;
             the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy&#xD;
&#xD;
         20. Participation in clinical trials with other anti-myeloma investigational agents not&#xD;
             included in this trial, within 14 days of the start of this trial and throughout the&#xD;
             duration of this trial&#xD;
&#xD;
         21. Radiation therapy within 2 weeks before randomization. Enrolment of subjects who&#xD;
             require concurrent radiotherapy (which must be localized in its field size) should be&#xD;
             deferred until the radiotherapy is completed and 2 weeks have elapsed since the last&#xD;
             date of therapy.&#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>Peter O'Gorman, Dr</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mater Misericordiae University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital Waterford</name>
      <address>
        <city>Waterford</city>
        <state>Co Waterford</state>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cork University Hospital</name>
      <address>
        <city>Cork</city>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beaumont Hospital</name>
      <address>
        <city>Dublin</city>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mater Misericordiae University Hospital</name>
      <address>
        <city>Dublin</city>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St James's Hospital</name>
      <address>
        <city>Dublin</city>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Galway</name>
      <address>
        <city>Galway</city>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Limerick</name>
      <address>
        <city>Limerick</city>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Midlands Regional Hospital</name>
      <address>
        <city>Tullamore</city>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Ireland</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>August 11, 2014</study_first_submitted>
  <study_first_submitted_qc>August 15, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 18, 2014</study_first_posted>
  <last_update_submitted>July 16, 2020</last_update_submitted>
  <last_update_submitted_qc>July 16, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 17, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Myeloma</mesh_term>
    <mesh_term>Neoplasms, Plasma Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dexamethasone</mesh_term>
    <mesh_term>Lenalidomide</mesh_term>
    <mesh_term>Bortezomib</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02219178
org study id: CTRIAL-IE (ICORG) 13-17
secondary id: 2013-005008-32
nct id: NCT02219178
lead sponsor: 
has dmc: No
This study aims to evaluate the overall response rate after 4 cycles and the best response to
      induction therapy with combination of lenalidomide, subcutaneous bortezomib, and
      dexamethasone (RsqVD) in patients with newly diagnosed multiple myeloma.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: To evaluate the overall response rate (ORR) after 4 induction cycles
time frame: After 4 cycles (84 days)
description: To evaluate the overall response rate (ORR) after 4 induction cycles and the best response to induction therapy with the combination of lenalidomide, subcutaneous (SQ) bortezomib, and dexamethasone (RsqVD) in patients with newly diagnosed multiple myeloma.
measure: a) To evaluate the rate and severity of Peripheral Neuropathy (PN) of SQ bortezomib in combination with lenalidomide, and dexamethasone after the 4th and after the final cycle of induction therapy.
time frame: After 4 cycles (84 days)
description: Evaluate the rate and severity of Peripheral Neuropathy of SQ bortezomib in combination with lenalidomide, and dexamethasone after the 4th and after the final cycle of induction therapy
measure: Progression of disease
time frame: Duration of the study, expected to be approximately 3 years
description: Evaluate the time to progression
measure: Progression free survival
time frame: Duration of the study, expected to be approximately 3 years
description: Evaluate progression free survival
measure: Duration of response
time frame: Duration of the study, expected to be approximately 3 years
arm group label: RsqVD
arm group type: Experimental
description: Oral lenalidomide 25mg days 1 - 14 of 21 day schedule Subcutaneous bortezomib 1.3mg/m2 days 1, 4, 8, 11 of 21 day schedule Oral dexamethasone 20mg on days 1, 2, 4, 5, 8, 9, 11, 12 of 21 day schedule
intervention type: Drug
intervention name: lenalidomide
description: 25mg days 1 - 14 of 21 day schedule
arm group label: RsqVD
other name: Revlimid
intervention type: Drug
intervention name: Subcutaneous bortezomib
description: 1.3mg/m2 days 1, 4, 8, 11 of 21 day schedule
arm group label: RsqVD
other name: Velcade
intervention type: Drug
intervention name: Dexamethasone
description: 20mg on days 1, 2, 4, 5, 8, 9, 11, 12 of 21 day schedule
arm group label: RsqVD
other name: Decadron
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Peter O'Gorman, Dr
role: Principal Investigator
affiliation: Mater Misericordiae University Hospital
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Ireland
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Dexamethasone
mesh term: Lenalidomide
mesh term: Bortezomib