<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/NCT02215980</url>
  </required_header>
  <id_info>
    <org_study_id>RV-MM-PI-0752</org_study_id>
    <nct_id>NCT02215980</nct_id>
  </id_info>
  <brief_title>STUDY TO DETERMINE THE EFFICACY AND SAFETY OF STANDARD SCHEDULE VERSUS A NEW ALGORITHM OF DOSE REDUCTIONS IN ELDERLY AND UNFIT NEWLY DIAGNOSED MULTIPLE MYELOMA PATIENTS RECEIVING LENALIDOMIDE PLUS STEROIDS</brief_title>
  <official_title>A PHASE III, MULTICENTRE, RANDOMIZED, CONTROLLED STUDY TO DETERMINE THE EFFICACY AND SAFETY OF STANDARD SCHEDULE VERSUS A NEW ALGORITHM OF DOSE REDUCTIONS IN ELDERLY AND UNFIT NEWLY DIAGNOSED MULTIPLE MYELOMA PATIENTS RECEIVING LENALIDOMIDE PLUS STEROIDS</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fondazione EMN Italy Onlus</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fondazione EMN Italy Onlus</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This protocol is a phase III multicenter, randomized, controlled study designed to assess the&#xD;
      safety and the efficacy of standard schedule versus a new algoritm of dose reductions in&#xD;
      elderly and unfit newly diagnosed Multiple Myeloma (MM) patients receiving lenalidomide plus&#xD;
      steroids.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      TREATMENT PERIOD:&#xD;
&#xD;
      Arm A: Rd&#xD;
&#xD;
        -  Lenalidomide: at the dose of 25 mg/daily as oral administration (PO) on days 1-21.&#xD;
&#xD;
        -  Dexamethasone: at the dose of 20 mg as oral administration (PO) once weekly. Each cycle&#xD;
           will be repeated every 28 days until progression or intolerance.&#xD;
&#xD;
      Arm B: Rd-R (reduced)&#xD;
&#xD;
        -  Lenalidomide: at the dose of 25 mg/daily as oral administration (PO) on days 1-21&#xD;
&#xD;
        -  Dexamethasone: at the dose of 20 mg as oral administration (PO) once weekly. Each cycle&#xD;
           will be repeated every 28 days, for a total of 9 cycles.&#xD;
&#xD;
      Maintenance until progression or intolerance:&#xD;
&#xD;
      - Lenalidomide: 10 mg/daily on days 1-21 of each 28-day cycle&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">July 2014</start_date>
  <completion_date type="Anticipated">July 2024</completion_date>
  <primary_completion_date type="Actual">July 2022</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Event-free survival</measure>
    <time_frame>3 years</time_frame>
    <description>Determine the Event-free survival defined as:&#xD;
Progression&#xD;
Death for any cause&#xD;
Discontinuation of lenalidomide therapy&#xD;
Occurrence of any haematological grade 4 or non-haematological grade 3-4 adverse events (AES), including Secondary Primary Malignancies (SPMs)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to progression (TTP)</measure>
    <time_frame>5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall response rate (ORR)</measure>
    <time_frame>5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to response (TTR)</measure>
    <time_frame>5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DOR)</measure>
    <time_frame>5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to the next therapy (TNT)</measure>
    <time_frame>5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of dose reduction and drug discontinuation</measure>
    <time_frame>5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health care cost</measure>
    <time_frame>5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation between tumor response and outcome with baseline prognostic factors</measure>
    <time_frame>5 years</time_frame>
    <description>Analysis of tumor response and outcome stratification by prognostic factors</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life assessment (HRQOL)</measure>
    <time_frame>5 years</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">210</enrollment>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Lenalidomide: at the dose of 25 mg/daily as oral administration (PO) on days 1-21.&#xD;
Dexamethasone: at the dose of 20 mg as oral administration (PO) once weekly. Each cycle will be repeated every 28 days until progression or intolerance.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Lenalidomide: at the dose of 25 mg/daily as oral administration (PO) on days 1-21&#xD;
Dexamethasone: at the dose of 20 mg as oral administration (PO) once weekly. Each cycle will be repeated every 28 days, for a total of 9 cycles.&#xD;
Maintenance until progression or intolerance:&#xD;
- Lenalidomide: 10 mg/daily on days 1-21 of each 28-day cycle</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lenalidomide</intervention_name>
    <arm_group_label>A</arm_group_label>
    <arm_group_label>B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexamethasone</intervention_name>
    <arm_group_label>A</arm_group_label>
    <arm_group_label>B</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients &gt;65 years unfit and unsuitable, according to the investigator's opinion, to&#xD;
             receive approved first line treatments for newly diagnosed MM.&#xD;
&#xD;
          -  Patient is, in the investigator(s) opinion, willing and able to comply with the&#xD;
             protocol requirements.&#xD;
&#xD;
          -  Patient has given voluntary written informed consent before performance of any&#xD;
             study-related procedure not part of normal medical care, with the understanding that&#xD;
             consent may be withdrawn by the patient at any time without prejudice to their future&#xD;
             medical care.&#xD;
&#xD;
          -  Symptomatic MM based on standard CRAB criteria (5).&#xD;
&#xD;
          -  Patient has measurable disease, defined as follows: any quantifiable serum monoclonal&#xD;
             protein value (generally, but not necessarily, ≥ 0.5 g/dL of M-protein) and, where&#xD;
             applicable, urine light-chain excretion of &gt;200 mg/24 hours. For patients with oligo&#xD;
             or non-secretory MM, it is required that they have measurable plasmacytoma &gt; 2 cm as&#xD;
             determined by clinical examination or applicable radiographs (i.e. MRI, CT-Scan) or an&#xD;
             abnormal free light chain ratio (n.v.: 0.26-1.65). We anticipate that less than 10% of&#xD;
             patients admitted to this study will be oligo- or non-secretory MM with free light&#xD;
             chains only in order to maximize interpretation of benefit results.&#xD;
&#xD;
          -  All randomized patients will be selected based on the use of 3 geriatric scales: IADL,&#xD;
             ADL, Charlson. Unfit patients with clinical sign of frailty (mild, moderate or severe&#xD;
             frailty), including need help for household tasks and personal care can be enrolled in&#xD;
             this trial (2,4).&#xD;
&#xD;
          -  In order to include patients who normally are not select for clinical trials, also&#xD;
             patients with the following abnormal laboratory values can be considered:&#xD;
&#xD;
               1. absolute neutrophil count (ANC) &lt; 1 x 10^9/L&#xD;
&#xD;
               2. platelet count &lt; 80 x 10^9/L&#xD;
&#xD;
               3. haemoglobin &lt; 8 g/dl.&#xD;
&#xD;
               4. aspartate transaminase (AST): &lt; 5 x the upper limit of normal (ULN).&#xD;
&#xD;
               5. alanine transaminase (ALT): &lt; 5 x the ULN.&#xD;
&#xD;
               6. total bilirubin: &gt; 1.5 x the ULN&#xD;
&#xD;
               7. calculated or measured creatinine clearance: &lt;30 mL/minute&#xD;
&#xD;
        The geriatric assessment evaluations will select unfit patients to be randomized regardless&#xD;
        of possible abnormal laboratory values at the study entry.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant or lactating females.&#xD;
&#xD;
          -  Male patients not agreeing to use an acceptable method for contraception (i.e., condom&#xD;
             or abstinence) for the duration of the study.&#xD;
&#xD;
          -  Females of childbearing potential not agreeing to use two acceptable methods for&#xD;
             contraception (e.g. a hormonal contraceptive, intrauterine device, diaphragm with&#xD;
             spermicide, condom with spermicide, or abstinence) for the duration of the study.&#xD;
&#xD;
          -  Previous treatment with anti-myeloma therapy (does not include radiotherapy,&#xD;
             bisphosphonates, or a single short course of steroid &lt; to the equivalent of&#xD;
             dexamethasone 40 mg/day for 4 days).&#xD;
&#xD;
          -  Any significant medical disease or conditions that, in the investigator's opinion, may&#xD;
             interfere with protocol adherence or subject's ability to give informed consent or&#xD;
             could place the subject at unacceptable risk.&#xD;
&#xD;
          -  Presence of clinical active infectious hepatitis type B or C, classified into&#xD;
             Child-Pugh class C (see Appendix V) and HIV.&#xD;
&#xD;
          -  Presence of acute active infection requiring antibiotics or infiltrative pulmonary&#xD;
             disease.&#xD;
&#xD;
          -  Contraindication to any of the required drugs or supportive treatments.&#xD;
&#xD;
          -  Presence of prior history of malignancies, other than multiple myeloma, with a life&#xD;
             expectancy &lt; 2 years.&#xD;
&#xD;
          -  Known allergy to any of the study medications, their analogues, or excipients in the&#xD;
             various formulations.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>65 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Fondazione EMN Italy Onlus</name>
      <address>
        <city>Torino</city>
        <zip>10126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>July 28, 2014</study_first_submitted>
  <study_first_submitted_qc>August 11, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 13, 2014</study_first_posted>
  <last_update_submitted>June 28, 2023</last_update_submitted>
  <last_update_submitted_qc>June 28, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 29, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Multiple myeloma</keyword>
  <keyword>Diagnosis</keyword>
  <keyword>Elderly and unfit patients</keyword>
  <keyword>Lenalidomide plus steroids</keyword>
  <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>
  </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/NCT02215980
org study id: RV-MM-PI-0752
nct id: NCT02215980
lead sponsor: 
has dmc: No
This protocol is a phase III multicenter, randomized, controlled study designed to assess the
      safety and the efficacy of standard schedule versus a new algoritm of dose reductions in
      elderly and unfit newly diagnosed Multiple Myeloma (MM) patients receiving lenalidomide plus
      steroids.
TREATMENT PERIOD:

      Arm A: Rd

        -  Lenalidomide: at the dose of 25 mg/daily as oral administration (PO) on days 1-21.

        -  Dexamethasone: at the dose of 20 mg as oral administration (PO) once weekly. Each cycle
           will be repeated every 28 days until progression or intolerance.

      Arm B: Rd-R (reduced)

        -  Lenalidomide: at the dose of 25 mg/daily as oral administration (PO) on days 1-21

        -  Dexamethasone: at the dose of 20 mg as oral administration (PO) once weekly. Each cycle
           will be repeated every 28 days, for a total of 9 cycles.

      Maintenance until progression or intolerance:

      - Lenalidomide: 10 mg/daily on days 1-21 of each 28-day cycle
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Event-free survival
time frame: 3 years
description: Determine the Event-free survival defined as:
Progression
Death for any cause
Discontinuation of lenalidomide therapy
Occurrence of any haematological grade 4 or non-haematological grade 3-4 adverse events (AES), including Secondary Primary Malignancies (SPMs)
measure: Progression-free survival (PFS)
time frame: 5 years
measure: Overall survival (OS)
time frame: 5 years
measure: Time to progression (TTP)
time frame: 5 years
measure: Overall response rate (ORR)
time frame: 5 years
measure: Time to response (TTR)
time frame: 5 years
measure: Duration of response (DOR)
time frame: 5 years
measure: Time to the next therapy (TNT)
time frame: 5 years
measure: Incidence of dose reduction and drug discontinuation
time frame: 5 years
measure: Health care cost
time frame: 5 years
measure: Correlation between tumor response and outcome with baseline prognostic factors
time frame: 5 years
description: Analysis of tumor response and outcome stratification by prognostic factors
measure: Quality of life assessment (HRQOL)
time frame: 5 years
arm group label: A
arm group type: Experimental
description: Lenalidomide: at the dose of 25 mg/daily as oral administration (PO) on days 1-21.
Dexamethasone: at the dose of 20 mg as oral administration (PO) once weekly. Each cycle will be repeated every 28 days until progression or intolerance.
arm group label: B
arm group type: Experimental
description: Lenalidomide: at the dose of 25 mg/daily as oral administration (PO) on days 1-21
Dexamethasone: at the dose of 20 mg as oral administration (PO) once weekly. Each cycle will be repeated every 28 days, for a total of 9 cycles.
Maintenance until progression or intolerance:
- Lenalidomide: 10 mg/daily on days 1-21 of each 28-day cycle
intervention type: Drug
intervention name: Lenalidomide
arm group label: A
arm group label: B
intervention type: Drug
intervention name: Dexamethasone
arm group label: A
arm group label: B
criteria: 
gender: All
minimum age: 65 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Italy
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Dexamethasone
mesh term: Lenalidomide