<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/NCT01729663</url>
  </required_header>
  <id_info>
    <org_study_id>CASVAC0401</org_study_id>
    <nct_id>NCT01729663</nct_id>
  </id_info>
  <brief_title>Phase II/III Clinical Study CSF470 Plus BCG Plus GM-CSF vs IFN Alpha 2b in Stage IIB, IIC and III Melanoma Patients</brief_title>
  <official_title>Randomized, Comparative Phase II/III Study Between Treatment With CSF470 Vaccine (Allogeneic, Irradiated) Plus BCG and MOLGRAMOSTIN (rhGM-CSF) as Adjuvants and Interferon-alfa 2b (IFN-ALPHA), in Stages IIB, IIC and III Post Surgery Cutaneous Melanoma Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Laboratorio Pablo Cassará S.R.L.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Fundacion Sales</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Agency for Scientific and Technological Promotion, Argentina</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Fundacion Cancer FUCA</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Council of Scientific and Technical Research, Argentina</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Instituto Nacional del Cáncer, Argentina</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Laboratorio Pablo Cassará S.R.L.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Randomized, open, Phase II-III study, comparative between treatment with CSF-470 vaccine ,&#xD;
      allogeneic, irradiated with BCG and molgramostin (rHuGM-CSF) as adjuvants and interferon alfa&#xD;
      2b (IFN-alpha2b) treatment , in stages IIB, IIC o III (AJCC) post-surgery cutaneous melanoma&#xD;
      patients. This study has been approved by ANMAT ( Administración Nacional de Medicamentos,&#xD;
      Alimentos y Tecnología Médica (ANMAT)), number 1556/2011 (www.anmat.gov.ar).&#xD;
&#xD;
      The study Institution is Instituto Médico Especializado Alexander Fleming, Ciudad Autónoma de&#xD;
      Buenos Aires, Argentina. The Sponsor is Laboratory Pablo Cassará (LPC, S.R.L.).&#xD;
&#xD;
      Study population include a total of 108 patients (72 patients will receive CSF470 vaccine and&#xD;
      36 patients will receive alpha IFN-alpha 2b) for a total of 24 months.&#xD;
&#xD;
      CSF-470 treatment will consist of four vaccine doses id injection (three weeks apart), then&#xD;
      one dose every two months for the first year and them every three months for the second year.&#xD;
&#xD;
      Each vaccine consist of a mixture of 17,6.106 melanoma cells, from four melanoma cell lines,&#xD;
      not genetically modified and lethally irradiated. As adjuvant BCG (120 µg prot) the first day&#xD;
      and rHuGM-CSF (Molgramostim, 400 µg, fractionated in four days doses) will be used.&#xD;
&#xD;
      IFN-alpha 2b treatment will consist of s.c. injection of 10 million units (MU) (5 t/w ) for&#xD;
      four weeks and then 5 MU (3t/w) for 23 months.&#xD;
&#xD;
      Both treatments will also compare quality of life (QOL) and study a possible correlation in&#xD;
      the CSF470 vaccine arm between the induced immune response and clinical outcome&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>April 2009</start_date>
  <primary_completion_date type="Anticipated">December 2018</primary_completion_date>
  <phase>Phase 2/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>Efficacy</measure>
    <time_frame>two years</time_frame>
    <description>OS, DFS, Partial or total remission (PR or CR)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>security</measure>
    <time_frame>two years</time_frame>
    <description>measured according to the NCI-Common Toxicity Criteria</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Quality of Life</measure>
    <time_frame>two years</time_frame>
    <description>QOL:evaluated with EORTC QLQ-C30 questionnaire; ECOG Performance status</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Induction of immune responses</measure>
    <time_frame>two years</time_frame>
    <description>Induction of immune responses associated to different vaccine doses for 2 years (Trial duration) ]Cellular immunity (DTH) - Humoral immunity</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">108</enrollment>
  <condition>Cutaneous Melanoma</condition>
  <arm_group>
    <arm_group_label>Interferon alpha 2 b</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Interferon alpha 2b treatment will consist of s.c. injection of 10 MU (5 t/w) for four weeks and then 5 MU (3t/w) for 23 months.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CSF470 vaccine, BCG, Molgramostim</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>CSF470 vaccine, BCG, Molgramostim&#xD;
CSF-470 treatment will consist of four vaccine doses id injection (three weeks apart), then one dose every two months for the first year and them every three months for the second year.&#xD;
Each vaccine consist of a mixture of 17,6.106 melanoma cells , from four melanoma cell lines, not genetically modified and lethally irradiated. As adjuvant BCG (120 µg prot) the first day and rhGM-CSF (Molgramostim 400 µg, fractionated in four days doses) will be used.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>CSF470 vaccine, BCG, Molgramostim</intervention_name>
    <arm_group_label>CSF470 vaccine, BCG, Molgramostim</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>interferon alpha 2b</intervention_name>
    <arm_group_label>Interferon alpha 2 b</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  histologically confirmed cutaneous melanoma stages IIB, IIC or III (AJCC)&#xD;
&#xD;
          -  patients non-detectable disease (NED) after surgery as asserted by CAT scans. Melanoma&#xD;
             pts with unknown primary tumor site could be included in the study&#xD;
&#xD;
          -  life expectancy &gt; 6 months&#xD;
&#xD;
          -  performance status (ECOG) 0 or 1&#xD;
&#xD;
          -  Time post surgery not more than 4 months&#xD;
&#xD;
          -  no chemotherapy, radiotherapy or any biological treatments prior to this study.&#xD;
&#xD;
          -  patients must have CATscans of brain, thorax, abdomen and pelvis in the 60 previous&#xD;
             days to trial enrolling&#xD;
&#xD;
          -  To have laboratory studies (no more than 15 days before entering the study)&#xD;
&#xD;
          -  laboratory eligibility criteria include: hematocrit: ≥35 (hemoglobin &gt; 10,5 gr %); WBC&#xD;
             count &gt; 3500/mm3, platelets &gt; 100.000/mm3, total and direct bilirubin, serum&#xD;
             oxalacetic transaminase and glutamic pyruvic transaminase &lt; 1.5 fold the upper normal&#xD;
             value; LDH ≤ 450 mU/ml&#xD;
&#xD;
          -  negative serology for HIV, anti-HCV and HBsAg&#xD;
&#xD;
          -  serum creatinine &lt; 2.0 mg %&#xD;
&#xD;
          -  all patients must give written informed consent before inclusion in the Study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant or breast-feeding women&#xD;
&#xD;
          -  Diabetes (Type I or II)&#xD;
&#xD;
          -  Antecedents of psychiatric diseases&#xD;
&#xD;
          -  Evidence of active infections&#xD;
&#xD;
          -  Antecedents of viral or autoimmune hepatitis&#xD;
&#xD;
          -  Previous autoimmune diseases&#xD;
&#xD;
          -  Morbid Obesity, defined as CMI (Corporal mass index)&gt;37 kg/m2 in women and &gt;40 kg/m2&#xD;
             in men.&#xD;
&#xD;
          -  Other diseases that require treatment with regular corticoids or non steroids&#xD;
             anti-inflammatory drugs&#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>José Mordoh, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Instituto Médico Alexander Fleming</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>José Mordoh, MD, PhD</last_name>
    <phone>54-11-6323-2900</phone>
    <phone_ext>2205</phone_ext>
    <email>jmordoh@alexanderfleming.org</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>María M Barrio, PhD</last_name>
    <phone>54-11-6323-2900</phone>
    <phone_ext>1110</phone_ext>
    <email>barrio.marcela@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Instituto Médico Alexander Fleming</name>
      <address>
        <city>Buenos Aires</city>
        <state>Capital Federal</state>
        <zip>1426</zip>
        <country>Argentina</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>José Mordoh, MD, PhD</last_name>
      <phone>44-11-6323-2900</phone>
      <phone_ext>2204</phone_ext>
      <email>jmordoh@leloir.org.ar</email>
    </contact>
    <investigator>
      <last_name>José Mordoh, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>María M Barrio, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Argentina</country>
  </location_countries>
  <verification_date>August 2015</verification_date>
  <study_first_submitted>November 14, 2012</study_first_submitted>
  <study_first_submitted_qc>November 19, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 20, 2012</study_first_posted>
  <last_update_submitted>August 31, 2015</last_update_submitted>
  <last_update_submitted_qc>August 31, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 2, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Laboratorio Pablo Cassará S.R.L.</investigator_affiliation>
    <investigator_full_name>José Mordoh</investigator_full_name>
    <investigator_title>MD, PhD</investigator_title>
  </responsible_party>
  <keyword>melanoma</keyword>
  <keyword>irradiated-allogeneic cells</keyword>
  <keyword>therapeutic vaccine</keyword>
  <keyword>Interferon alpha 2-b</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Melanoma</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>Molgramostim</mesh_term>
    <mesh_term>Sargramostim</mesh_term>
    <mesh_term>BCG Vaccine</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/NCT01729663
org study id: CASVAC0401
nct id: NCT01729663
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
Randomized, open, Phase II-III study, comparative between treatment with CSF-470 vaccine ,
      allogeneic, irradiated with BCG and molgramostin (rHuGM-CSF) as adjuvants and interferon alfa
      2b (IFN-alpha2b) treatment , in stages IIB, IIC o III (AJCC) post-surgery cutaneous melanoma
      patients. This study has been approved by ANMAT ( Administración Nacional de Medicamentos,
      Alimentos y Tecnología Médica (ANMAT)), number 1556/2011 (www.anmat.gov.ar).

      The study Institution is Instituto Médico Especializado Alexander Fleming, Ciudad Autónoma de
      Buenos Aires, Argentina. The Sponsor is Laboratory Pablo Cassará (LPC, S.R.L.).

      Study population include a total of 108 patients (72 patients will receive CSF470 vaccine and
      36 patients will receive alpha IFN-alpha 2b) for a total of 24 months.

      CSF-470 treatment will consist of four vaccine doses id injection (three weeks apart), then
      one dose every two months for the first year and them every three months for the second year.

      Each vaccine consist of a mixture of 17,6.106 melanoma cells, from four melanoma cell lines,
      not genetically modified and lethally irradiated. As adjuvant BCG (120 µg prot) the first day
      and rHuGM-CSF (Molgramostim, 400 µg, fractionated in four days doses) will be used.

      IFN-alpha 2b treatment will consist of s.c. injection of 10 million units (MU) (5 t/w ) for
      four weeks and then 5 MU (3t/w) for 23 months.

      Both treatments will also compare quality of life (QOL) and study a possible correlation in
      the CSF470 vaccine arm between the induced immune response and clinical outcome
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Efficacy
time frame: two years
description: OS, DFS, Partial or total remission (PR or CR)
measure: security
time frame: two years
description: measured according to the NCI-Common Toxicity Criteria
measure: Quality of Life
time frame: two years
description: QOL:evaluated with EORTC QLQ-C30 questionnaire; ECOG Performance status
measure: Induction of immune responses
time frame: two years
description: Induction of immune responses associated to different vaccine doses for 2 years (Trial duration) ]Cellular immunity (DTH) - Humoral immunity
arm group label: Interferon alpha 2 b
arm group type: Active Comparator
description: Interferon alpha 2b treatment will consist of s.c. injection of 10 MU (5 t/w) for four weeks and then 5 MU (3t/w) for 23 months.
arm group label: CSF470 vaccine, BCG, Molgramostim
arm group type: Experimental
description: CSF470 vaccine, BCG, Molgramostim
CSF-470 treatment will consist of four vaccine doses id injection (three weeks apart), then one dose every two months for the first year and them every three months for the second year.
Each vaccine consist of a mixture of 17,6.106 melanoma cells , from four melanoma cell lines, not genetically modified and lethally irradiated. As adjuvant BCG (120 µg prot) the first day and rhGM-CSF (Molgramostim 400 µg, fractionated in four days doses) will be used.
intervention type: Biological
intervention name: CSF470 vaccine, BCG, Molgramostim
arm group label: CSF470 vaccine, BCG, Molgramostim
intervention type: Drug
intervention name: interferon alpha 2b
arm group label: Interferon alpha 2 b
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: José Mordoh, MD, PhD
role: Principal Investigator
affiliation: Instituto Médico Alexander Fleming
last name: José Mordoh, MD, PhD
phone: 54-11-6323-2900
phone ext: 2205
email: jmordoh@alexanderfleming.org
last name: María M Barrio, PhD
phone: 54-11-6323-2900
phone ext: 1110
email: barrio.marcela@gmail.com
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
country: Argentina
responsible party type: Principal Investigator
investigator affiliation: Laboratorio Pablo Cassará S.R.L.
investigator full name: José Mordoh
investigator title: MD, PhD
mesh term: Melanoma
mesh term: Interferons
mesh term: Interferon-alpha
mesh term: Interferon alpha-2
mesh term: Molgramostim
mesh term: Sargramostim
mesh term: BCG Vaccine