<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/NCT02201459</url>
  </required_header>
  <id_info>
    <org_study_id>2013.837</org_study_id>
    <nct_id>NCT02201459</nct_id>
  </id_info>
  <brief_title>Nilotinib ± Peg-IFN for First Line Chronic Phase CML Patients</brief_title>
  <acronym>PETALs</acronym>
  <official_title>Randomized Multicenter Phase III Study Comparing the Rate of Molecular Response 4.5 at 12 Months in Newly Diagnosed Philadelphia Positive Chronic Phase Chronic Myelogenous Leukemia Patients Receiving Either Frontline Nilotinib 600 mg Daily or Nilotinib 600 mg Daily Combined to Pegylated Interferon-alfa 2a (Peg-IFN)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospices Civils de Lyon</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Novartis</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Hospices Civils de Lyon</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a phase III trial comparing, for newly diagnosed chronic phase CML patients,&#xD;
      nilotinib 600 mg BID as a standard arm and nilotinib 600 mg BID combined to interferon alfa 2&#xD;
      a (pegylated form improving tolerance and maybe enhancing is efficacy) at increased doses for&#xD;
      a total of 24 months of combination, in a 1:1 randomized manner. The assessment for the&#xD;
      primary efficacy endpoint will be performed at 12 months (since nilotinib initiation) and is&#xD;
      the rate patients obtaining MR4.5 will be measured at this time point.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>August 2014</start_date>
  <completion_date type="Anticipated">August 2019</completion_date>
  <primary_completion_date type="Anticipated">January 2018</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>Molecular response (MR) 4.5 at 12 months of nilotinib 300 mg twice a day versus a combination of low-dose Peg-Interferon (Peg-IFN) to nilotinib 300 mg twice a day in newly diagnosed CP-CML Chronic Phase Chronic Myelogenous Leukemia patients.</measure>
    <time_frame>12 months</time_frame>
    <description>Centralised assessment of the BCR-ABL transcripts at 12 months since nilotinib initiation</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Molecular Response 4.5 at 1, 2, 3, 6, 9, 12 months of nilotinib, and duration of MR4.5 during the second year of treatment (18, 24 and 36 months).</measure>
    <time_frame>36 months</time_frame>
    <description>Centralised assessment of the BCR-ABL transcripts every month for 3 months and every three months until 12 months and thereafter every 6 months until 36 months assessment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Major Molecular Response at 1, 2, 3, 6, 9, 12 months of nilotinib, and duration of MMR during the second year of treatment (18, 24 and 36 months).</measure>
    <time_frame>36 months</time_frame>
    <description>Centralised assessment of the BCR-ABL transcripts every month for 3 months and every three months until 12 months and thereafter every 6 months until 36 months assessment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of patients with BCR-ABL/ABL (IS) ≥10% at 3 months.</measure>
    <time_frame>3 months after nilotinib initiation</time_frame>
    <description>Centralised assessment of the BCR-ABL transcripts at 3 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of CCyR (complete cytogenetic responses: bone marrow Philadelphie positive at 0 % on at least 20 metaphases) at 3, 6, 12 months of nilotinib.</measure>
    <time_frame>Assessment at 3, 6 and 12 months</time_frame>
    <description>Local bone marrow cytogenetic assessment (on 20 metaphases)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety of the nilotinib combined to Peg-IFN or not (hematological and non-hematological adverse events (AE) graded according to the NCI CTC AE v3).</measure>
    <time_frame>36 months</time_frame>
    <description>Continuous evaluation of the AEs and SAEs reported during 36 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life of patients treated in both arms</measure>
    <time_frame>36 months</time_frame>
    <description>EORTC-QLQ C30 and C24 questionnaire at months -1 (Arm B), month 0, 1, 6, 12, 24, 36.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Doses-reductions/interruptions of drugs in both arms. Mean daily doses of nilotinib and Peg-IFN administered.</measure>
    <time_frame>24 months for Peg-IFN, and 36 months for both drugs</time_frame>
    <description>Continuous recording of dose intensity along the study for 24-36 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compliance to drugs in each arms</measure>
    <time_frame>36 months</time_frame>
    <description>Morisky questionnaire to be fulfilled at 1, 6, 12, 24 and 36 months after nilotinib initiation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Molecular relapse rate at 6 and 12 months after nilotinib withdrawal in patients obtaining 2-year stable MR4.5.</measure>
    <time_frame>36 months</time_frame>
    <description>Local (but standardized) assessment of the BCR-ABL transcripts every months for 3 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Event-free survival.</measure>
    <time_frame>36 months</time_frame>
    <description>Survival since randomization without any event defined as loss of CHR, loss of PCyR or CCyR, death from any cause, progression towards accelerated phase or blast crisis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival</measure>
    <time_frame>36 months</time_frame>
    <description>Survival without progression towards accelerated of blast phase, death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival.</measure>
    <time_frame>36 months</time_frame>
    <description>Survival without death from any cause</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Chronic Myeloid Leukemia</condition>
  <arm_group>
    <arm_group_label>Nilotinib</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Control arm, this compound been licensed in this indication.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Peg-IFN alfa 2a (Pegasys®) and Nilotinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Arm testing the efficacy of a combination of nilotinib and Peg-IFN alfa 2a as frontline therapy for first line chronic phase CML patients.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nilotinib (Tasigna ®), capsules of 150 mg</intervention_name>
    <description>Nilotinib 2 capsules of 150 mg orally twice daily at 12 hours difference, fasting (minimum 1 hour before or 2 hours after a meal) for at least 36 months</description>
    <arm_group_label>Nilotinib</arm_group_label>
    <arm_group_label>Peg-IFN alfa 2a (Pegasys®) and Nilotinib</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nilotinib (Tasigna ®) and Pegylated interferon alfa 2a (Pegasys®)</intervention_name>
    <description>Nilotinib 2 capsules of 150 mg orally twice daily at 12 hours difference, fasting (minimum 1 hour before or 2 hours after a meal) for at least 36 months and&#xD;
Pegylated interferon alfa 2a subcutaneously once a week (auto-injection syringes of 135 and 90 micrograms) at 30 micrograms/week the first month alone (= priming procedure), then at 30 micrograms/2weeks the first month of combination to nilotinib and then at 45 micrograms/week thereafter until month 24 after nilotinib initiation.</description>
    <arm_group_label>Peg-IFN alfa 2a (Pegasys®) and Nilotinib</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male and female patients&#xD;
&#xD;
          -  CP-CML, positive Philadelphia chromosome or positive BCR-ABL (M-bcr transcript),&#xD;
             diagnosed less than 3 months prior to study entry&#xD;
&#xD;
          -  Age of at least 18 years-old and less than 65 years&#xD;
&#xD;
          -  Patient for whom treatment with Nilotinib is expected&#xD;
&#xD;
          -  No other CML treatment except for hydroxyurea and/or anagrelide&#xD;
&#xD;
          -  No previous TKI treatment.&#xD;
&#xD;
          -  No previous treatment with IFN even for other purposes.&#xD;
&#xD;
          -  SGOT and SGPT &lt; 2.5 UNL&#xD;
&#xD;
          -  Serum creatinine &lt; 2 UNL&#xD;
&#xD;
          -  No planned allogeneic stem cell transplantation&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
          -  ECOG score 0 to 2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Contra-indication to IFN&#xD;
&#xD;
          -  Transcripts other than M-Bcr&#xD;
&#xD;
          -  Pregnancy, lactation&#xD;
&#xD;
          -  HIV positivity, chronic hepatitis B or C.&#xD;
&#xD;
          -  Prior or concurrent malignancy other than CML (exceptions to be mentioned)&#xD;
&#xD;
          -  History of arterial occlusive disease or (peripheral, carotids or severe coronary&#xD;
             heart disease).&#xD;
&#xD;
          -  Permanent elevation of total cholesterol and triglycerides despite treatment&#xD;
&#xD;
          -  Severe psychiatric/neurological disease (previous or ongoing)&#xD;
&#xD;
          -  Concomitant auto-immune disease&#xD;
&#xD;
          -  Other investigational product ongoing&#xD;
&#xD;
          -  Ongoing immunosuppressive treatment&#xD;
&#xD;
          -  Ongoing treatment at risk for inducing torsades de pointes&#xD;
&#xD;
          -  QTcF &gt; 450ms despite correction of predisposing factors (i.e electrolytes…)&#xD;
&#xD;
          -  Congenital long QTcF&#xD;
&#xD;
          -  Unstabilised thyroid disorder&#xD;
&#xD;
          -  No health insurance coverage&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Franck NICOLINI, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hopsices Civils de Lyon</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Madeleine ETIENNE, CRA</last_name>
    <phone>4 78 86 22 32</phone>
    <phone_ext>+33</phone_ext>
    <email>madeleine.etienne@chu-lyon.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>jérémy MONFRAY, CRA</last_name>
    <phone>4 78 86 22 27</phone>
    <phone_ext>+33</phone_ext>
    <email>jeremy.monfray@chu-lyon.fr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Franck NICOLINI</name>
      <address>
        <city>Lyon</city>
        <zip>04 78 86 22 50</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Franck Nicolini, MD</last_name>
      <phone>4 78 86 22 50</phone>
      <phone_ext>33</phone_ext>
      <email>franck-emmanuel.nicolini@chu-lyon.fr</email>
    </contact>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>August 2014</verification_date>
  <study_first_submitted>June 24, 2014</study_first_submitted>
  <study_first_submitted_qc>July 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 28, 2014</study_first_posted>
  <last_update_submitted>August 6, 2014</last_update_submitted>
  <last_update_submitted_qc>August 6, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 7, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Peg-IFN, nilotinib, MR4.5, CML, chronic phase, first-line</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Leukemia, Myelogenous, Chronic, BCR-ABL Positive</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Interferons</mesh_term>
    <mesh_term>Interferon-alpha</mesh_term>
    <mesh_term>Interferon alpha-2</mesh_term>
    <mesh_term>Peginterferon alfa-2a</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/NCT02201459
org study id: 2013.837
nct id: NCT02201459
lead sponsor: 
collaborator: 
has dmc: Yes
This is a phase III trial comparing, for newly diagnosed chronic phase CML patients,
      nilotinib 600 mg BID as a standard arm and nilotinib 600 mg BID combined to interferon alfa 2
      a (pegylated form improving tolerance and maybe enhancing is efficacy) at increased doses for
      a total of 24 months of combination, in a 1:1 randomized manner. The assessment for the
      primary efficacy endpoint will be performed at 12 months (since nilotinib initiation) and is
      the rate patients obtaining MR4.5 will be measured at this time point.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Molecular response (MR) 4.5 at 12 months of nilotinib 300 mg twice a day versus a combination of low-dose Peg-Interferon (Peg-IFN) to nilotinib 300 mg twice a day in newly diagnosed CP-CML Chronic Phase Chronic Myelogenous Leukemia patients.
time frame: 12 months
description: Centralised assessment of the BCR-ABL transcripts at 12 months since nilotinib initiation
measure: Molecular Response 4.5 at 1, 2, 3, 6, 9, 12 months of nilotinib, and duration of MR4.5 during the second year of treatment (18, 24 and 36 months).
time frame: 36 months
description: Centralised assessment of the BCR-ABL transcripts every month for 3 months and every three months until 12 months and thereafter every 6 months until 36 months assessment.
measure: Major Molecular Response at 1, 2, 3, 6, 9, 12 months of nilotinib, and duration of MMR during the second year of treatment (18, 24 and 36 months).
time frame: 36 months
description: Centralised assessment of the BCR-ABL transcripts every month for 3 months and every three months until 12 months and thereafter every 6 months until 36 months assessment.
measure: Rate of patients with BCR-ABL/ABL (IS) ≥10% at 3 months.
time frame: 3 months after nilotinib initiation
description: Centralised assessment of the BCR-ABL transcripts at 3 months.
measure: Rate of CCyR (complete cytogenetic responses: bone marrow Philadelphie positive at 0 % on at least 20 metaphases) at 3, 6, 12 months of nilotinib.
time frame: Assessment at 3, 6 and 12 months
description: Local bone marrow cytogenetic assessment (on 20 metaphases)
measure: Safety of the nilotinib combined to Peg-IFN or not (hematological and non-hematological adverse events (AE) graded according to the NCI CTC AE v3).
time frame: 36 months
description: Continuous evaluation of the AEs and SAEs reported during 36 months
measure: Quality of life of patients treated in both arms
time frame: 36 months
description: EORTC-QLQ C30 and C24 questionnaire at months -1 (Arm B), month 0, 1, 6, 12, 24, 36.
measure: Doses-reductions/interruptions of drugs in both arms. Mean daily doses of nilotinib and Peg-IFN administered.
time frame: 24 months for Peg-IFN, and 36 months for both drugs
description: Continuous recording of dose intensity along the study for 24-36 months.
measure: Compliance to drugs in each arms
time frame: 36 months
description: Morisky questionnaire to be fulfilled at 1, 6, 12, 24 and 36 months after nilotinib initiation.
measure: Molecular relapse rate at 6 and 12 months after nilotinib withdrawal in patients obtaining 2-year stable MR4.5.
time frame: 36 months
description: Local (but standardized) assessment of the BCR-ABL transcripts every months for 3 months.
measure: Event-free survival.
time frame: 36 months
description: Survival since randomization without any event defined as loss of CHR, loss of PCyR or CCyR, death from any cause, progression towards accelerated phase or blast crisis.
measure: Progression-free survival
time frame: 36 months
description: Survival without progression towards accelerated of blast phase, death.
measure: Overall survival.
time frame: 36 months
description: Survival without death from any cause
arm group label: Nilotinib
arm group type: Active Comparator
description: Control arm, this compound been licensed in this indication.
arm group label: Peg-IFN alfa 2a (Pegasys®) and Nilotinib
arm group type: Experimental
description: Arm testing the efficacy of a combination of nilotinib and Peg-IFN alfa 2a as frontline therapy for first line chronic phase CML patients.
intervention type: Drug
intervention name: Nilotinib (Tasigna ®), capsules of 150 mg
description: Nilotinib 2 capsules of 150 mg orally twice daily at 12 hours difference, fasting (minimum 1 hour before or 2 hours after a meal) for at least 36 months
arm group label: Nilotinib
arm group label: Peg-IFN alfa 2a (Pegasys®) and Nilotinib
intervention type: Drug
intervention name: Nilotinib (Tasigna ®) and Pegylated interferon alfa 2a (Pegasys®)
description: Nilotinib 2 capsules of 150 mg orally twice daily at 12 hours difference, fasting (minimum 1 hour before or 2 hours after a meal) for at least 36 months and
Pegylated interferon alfa 2a subcutaneously once a week (auto-injection syringes of 135 and 90 micrograms) at 30 micrograms/week the first month alone (= priming procedure), then at 30 micrograms/2weeks the first month of combination to nilotinib and then at 45 micrograms/week thereafter until month 24 after nilotinib initiation.
arm group label: Peg-IFN alfa 2a (Pegasys®) and Nilotinib
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Franck NICOLINI, MD
role: Principal Investigator
affiliation: Hopsices Civils de Lyon
last name: Madeleine ETIENNE, CRA
phone: 4 78 86 22 32
phone ext: +33
email: madeleine.etienne@chu-lyon.fr
last name: jérémy MONFRAY, CRA
phone: 4 78 86 22 27
phone ext: +33
email: jeremy.monfray@chu-lyon.fr
facility: 
status: Recruiting
contact: 
country: France
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Leukemia, Myelogenous, Chronic, BCR-ABL Positive
mesh term: Interferons
mesh term: Interferon-alpha
mesh term: Interferon alpha-2
mesh term: Peginterferon alfa-2a