<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/NCT01679860</url>
  </required_header>
  <id_info>
    <org_study_id>PTCL-062006-004234-33</org_study_id>
    <nct_id>NCT01679860</nct_id>
  </id_info>
  <brief_title>Intensive Chemo-immunotherapy as First Line Treatment in Adult Patients With Peripheral T- Cell Lymphoma</brief_title>
  <acronym>PTCL-06</acronym>
  <official_title>Intensive Chemo-immunotherapy as First-line Treatment in Adult Patients With Peripheral T-cell Lymphoma (PTCL)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fondazione IRCCS Istituto Nazionale dei Tumori, Milano</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fondazione IRCCS Istituto Nazionale dei Tumori, Milano</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Peripheral T cell lymphomas (PTCL) are a rare hematologic disease. Five-year overall survival&#xD;
      (OS) of PTCL patients (pts) ranges between 20 and 30%. Allogeneic stem cell transplantation&#xD;
      (allo-STC) may have a curative role for these pts but its toxicity is high when myeloablative&#xD;
      conditioning is used. Reduced intensity conditionings (RIC) can decrease transplant related&#xD;
      toxicity and mortality. The investigators have recently proved feasibility and potential&#xD;
      efficacy of a RIC regimen in relapsed PTCL patients.&#xD;
&#xD;
      We want to investigate whether it is possible to improve the outcome of alk negative PTCL&#xD;
      pts, stage II-IV at diagnosis, by intensifying the therapeutic approach.&#xD;
&#xD;
      The intensification will be obtained by combining intensive chemotherapy, alemtuzumab&#xD;
      (anti-CD52 humanised antibody) and auto- or allo-SCT in pts aged between 18 and 60 years&#xD;
      (Clinical Study A) or adding alemtuzumab to standard chemotherapy (CHOP) in pts aged between&#xD;
      61 and 70 years(Clinical Study B).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Inclusion criteria Clin A&#xD;
&#xD;
        -  Age ≥18 &lt; or =60 years (patients older than 60 years are excluded because of the&#xD;
           intensive chemotherapy and transplant procedures)&#xD;
&#xD;
        -  Histologically proven diagnosis of PTCL, including the following categories: PTCL-U&#xD;
           (peripheral T-cell lymphoma, unspecified), AILD-T (angioimmunoblastic-like T-cell&#xD;
           lymphoma), ALKneg ALCL (ALK-negative anaplastic large cell lymphoma),intestinal T - NHL&#xD;
&#xD;
        -  Advanced stage disease (stage II-IV) or stage I and aaIPI score ≥ 2&#xD;
&#xD;
        -  Written informed consent&#xD;
&#xD;
      Inclusion criteria Clin B&#xD;
&#xD;
        -  Age &gt;60 and ≤75 years (patients older than 75 years are excluded because of the&#xD;
           intensive chemo-immunotherapy program)&#xD;
&#xD;
        -  Histological proven diagnosis of PTCL, including the following categories: PTCL-U&#xD;
           (peripheral T-cell lymphoma, unspecified), AILD-T (angioimmunoblastic-like T-cell&#xD;
           lymphoma), ALKneg ALCL (ALK-negative anaplastic large cell lymphoma), intestinal T - NHL&#xD;
&#xD;
        -  Advanced-stage disease (stage II-IV) or stage I and aaIPI score ≥ 2&#xD;
&#xD;
        -  Informed written consent&#xD;
&#xD;
      In clinical study A (Clin A) we are planning to evaluate the efficacy and the feasibility of&#xD;
      an intensified chemo-immunotherapy program including auto-SCT or RIC allo-SCT in advanced&#xD;
      stage PTCL pts ≥ 18 and &lt; or = 60 years.&#xD;
&#xD;
      In clinical study B (Clin B) we intend to verify the efficacy and the feasibility of a&#xD;
      combined immuno-chemotherapy approach in a subset of elderly pts aged &gt; 60 and &lt; or = 75&#xD;
      years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2006</start_date>
  <completion_date type="Actual">August 2012</completion_date>
  <primary_completion_date type="Actual">December 2011</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Efficacy</measure>
    <time_frame>one year</time_frame>
    <description>number of clinical responses</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>evaluation of OS (overall survival)</measure>
    <time_frame>4 years</time_frame>
    <description>OS time is calculated from patients enrollment to death for all causes; censored cases are pts alive at the date of last follow-up assessment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DFS (Disease Free Survival)</measure>
    <time_frame>4 years</time_frame>
    <description>DFS time is the interval between CR achievement and the first disease relapse or death regardless of the cause.Definition of disease response/progression will be performed according to the criteria published by Juweid et al.(J Clin Oncol. 2005; 23: 4652-61)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TRM (Treatment Related Mortality)</measure>
    <time_frame>4 years</time_frame>
    <description>TRM will be analysed by computing the corresponding crude cumulative incidence curve, considering disease-related death as competing event.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">92</enrollment>
  <condition>Lymphoma, T-Cell, Peripheral</condition>
  <arm_group>
    <arm_group_label>Clin A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Clin A. CHOP-Campath (CHOP-C) for 2 cycles , Hyper-C-Hidam for 2 cycles and auto-SCT (stem cell transplantation) or RIC allo-SCT in advanced stage PTCL pts ≥ 18 and ≤ 60 years</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Clin B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Clin B: CHOP-Campath (CHOP-C) for 6 cycles . It is a combined immunochemotherapy approach in a subset of elderly pts aged &gt; 60 ≤ 75 years</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Clin A. CHOP-CAMPATH (Chemo-immunotherapy) + SCT</intervention_name>
    <description>Clin A:&#xD;
CHOP-Campath (CHOP-C) for 2 cycles (every 21 days): Doxorubicin 50mg/m2 day +1, Vincristin 1.4mg/m2 day +1, Cyclophosphamide 750mg/m2 day +1, prednisone 100mg/m2 PO on days +1 to +5; Campath-1H (alemtuzumab) dose escalation 3-10-20mg IV days - 2, - 1, 0 (first CHOP-C) or 30mg SC day 0 (second CHOP-C). Methotrexate 12.5mg IT, Ara-C 40mg IT, Dexamethasone 4mg IT on days + 1 and 21 (first and second CHOP-C).&#xD;
HYPER-C-HiDAM for 2 cycles: Methotrexate 1.5gr/m2 day +1; Cyclophosphamide 300mg/m2 every 12 hours days +2-3-4; ARA-C 2gr/m2 every 12 hours days +2-3-4; G-CSF 5μcg/kg/day starting from day +5 until peripheral blood stem cell harvest&#xD;
Myeloablative regimen followed by autologous transplantation or Reduced intensity conditioning followed by allogeneic transplantation.</description>
    <arm_group_label>Clin A</arm_group_label>
    <other_name>Mab - Campath (Alemtuzumab)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Clin B (CHOP- CAMPATH) Chemo-immunotherapy</intervention_name>
    <description>Clin B:&#xD;
CHOP-Campath (CHOP-C) for 6 cycles (every 21 days): Doxorubicin 50mg/m2 day +1, Vincristin 1.4mg/m2 day +1, Cyclophosphamide 750mg/m2 day +1, prednisone 100mg/m2 PO from day +1 to day +5¸ Campath-1H (alemtuzumab) 3-10mg IV on days - 1 and 0 ( first CHOP-C course) or 10mg SC on day 0 (for the following 5 C-CHOP courses). Methotrexate 12.5mg IT, Ara-C 40mg IT, Dexamethasone 4mg IT on day +1 of each CHOP-C course.</description>
    <arm_group_label>Clin B</arm_group_label>
    <other_name>Mab- Campath (Alemtuzumab)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥18 &lt;60 years (patients older than 60 years are excluded because of the intensive&#xD;
             chemotherapy and transplant procedures)&#xD;
&#xD;
          -  Histologically proven diagnosis of PTCL, including the following categories: PTCL-U&#xD;
             (peripheral T-cell lymphoma, unspecified), AILD-T (angioimmunoblastic-like T-cell&#xD;
             lymphoma), ALKneg ALCL (ALK-negative anaplastic large cell lymphoma),intestinal T -&#xD;
             NHL&#xD;
&#xD;
          -  Advanced stage disease (stage II-IV) or stage I and aaIPI score ≥ 2&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Histological PTCL subset other than PTCL-U, AILD-T ALCL-ALKneg, intestinal T - NHL&#xD;
&#xD;
          -  Central nervous system localization&#xD;
&#xD;
          -  Positive serologic markers for human immunodeficiency virus (HIV), hepatitis B virus&#xD;
             (HBV), and hepatitis C virus (HCV) infection&#xD;
&#xD;
          -  Serum bilirubin levels &gt; 2 the upper normal limit&#xD;
&#xD;
          -  Clearance of creatinine &lt; 50 ml/min&#xD;
&#xD;
          -  DLCO &lt; 50%&#xD;
&#xD;
          -  Ejection fraction &lt; 45% (or myocardial infarction in the last 12 months)&#xD;
&#xD;
          -  Pregnancy or lactation&#xD;
&#xD;
          -  Patient not agreeing to take adequate contraceptive measures during the study&#xD;
&#xD;
          -  Psychiatric disease&#xD;
&#xD;
          -  Any active, uncontrolled infection&#xD;
&#xD;
          -  Type I hypersensitivity or anaphylactic reactions to proteins drugs&#xD;
&#xD;
          -  Active secondary malignancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>paolo corradini</last_name>
    <role>Principal Investigator</role>
    <affiliation>fondazione IRCCS istituto nazionale tumori Milano</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Azienda Ospedaliera S. Luigi</name>
      <address>
        <city>Orbassano</city>
        <state>Torino</state>
        <zip>10043</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale SS. Antonio e Biagio e Cesare Arrigo</name>
      <address>
        <city>Alessandria</city>
        <zip>15100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Ancona - Division of Hematology</name>
      <address>
        <city>Ancona</city>
        <zip>62020</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale Riuniti, Bergamo - Division of Hematology</name>
      <address>
        <city>Bergamo</city>
        <zip>24128</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale Generale Regionale Bolzano</name>
      <address>
        <city>Bolzano</city>
        <zip>39100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spedali Civili di Brescia</name>
      <address>
        <city>Brescia</city>
        <zip>25123</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedale Vittorio Emanuele Ferrarorro S. Bambino- Università di Catania</name>
      <address>
        <city>Catania</city>
        <zip>94124</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale S. Croce - Division of Hematology</name>
      <address>
        <city>Cuneo</city>
        <zip>12100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IRCCS Ospedale Maggiore Policlinico di Milano</name>
      <address>
        <city>Milano</city>
        <zip>20122</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale San Raffaele, Milano - Division of Hematology</name>
      <address>
        <city>Milan</city>
        <zip>20100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Division of Hematology - Fondazione IRCCS Istituto Nazionale Tumori</name>
      <address>
        <city>Milan</city>
        <zip>20133</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale Cervello - Bone Marrow Transplantation Unit</name>
      <address>
        <city>Palermo</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale San Carlo</name>
      <address>
        <city>Potenza</city>
        <zip>85100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda OspedalieraSan Giovanni Battista</name>
      <address>
        <city>Torino</city>
        <zip>10126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Università di Torino- Azienda Ospedaliera S. Giovanni Battista</name>
      <address>
        <city>Torino</city>
        <zip>10126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Policlinico Universitario Udine</name>
      <address>
        <city>Udine</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Policlinico di Verona</name>
      <address>
        <city>Verona</city>
        <zip>37134</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>September 2012</verification_date>
  <study_first_submitted>August 30, 2012</study_first_submitted>
  <study_first_submitted_qc>September 3, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 6, 2012</study_first_posted>
  <last_update_submitted>September 3, 2012</last_update_submitted>
  <last_update_submitted_qc>September 3, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 6, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Fondazione IRCCS Istituto Nazionale dei Tumori, Milano</investigator_affiliation>
    <investigator_full_name>Paolo Corradini</investigator_full_name>
    <investigator_title>Director Hematology and BMT Unit</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, T-Cell</mesh_term>
    <mesh_term>Lymphoma, T-Cell, Peripheral</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alemtuzumab</mesh_term>
    <mesh_term>Immunomodulating Agents</mesh_term>
    <mesh_term>Immunologic Factors</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/NCT01679860
org study id: PTCL-062006-004234-33
nct id: NCT01679860
lead sponsor: 
has dmc: Yes
Peripheral T cell lymphomas (PTCL) are a rare hematologic disease. Five-year overall survival
      (OS) of PTCL patients (pts) ranges between 20 and 30%. Allogeneic stem cell transplantation
      (allo-STC) may have a curative role for these pts but its toxicity is high when myeloablative
      conditioning is used. Reduced intensity conditionings (RIC) can decrease transplant related
      toxicity and mortality. The investigators have recently proved feasibility and potential
      efficacy of a RIC regimen in relapsed PTCL patients.

      We want to investigate whether it is possible to improve the outcome of alk negative PTCL
      pts, stage II-IV at diagnosis, by intensifying the therapeutic approach.

      The intensification will be obtained by combining intensive chemotherapy, alemtuzumab
      (anti-CD52 humanised antibody) and auto- or allo-SCT in pts aged between 18 and 60 years
      (Clinical Study A) or adding alemtuzumab to standard chemotherapy (CHOP) in pts aged between
      61 and 70 years(Clinical Study B).
Inclusion criteria Clin A

        -  Age ≥18 < or =60 years (patients older than 60 years are excluded because of the
           intensive chemotherapy and transplant procedures)

        -  Histologically proven diagnosis of PTCL, including the following categories: PTCL-U
           (peripheral T-cell lymphoma, unspecified), AILD-T (angioimmunoblastic-like T-cell
           lymphoma), ALKneg ALCL (ALK-negative anaplastic large cell lymphoma),intestinal T - NHL

        -  Advanced stage disease (stage II-IV) or stage I and aaIPI score ≥ 2

        -  Written informed consent

      Inclusion criteria Clin B

        -  Age >60 and ≤75 years (patients older than 75 years are excluded because of the
           intensive chemo-immunotherapy program)

        -  Histological proven diagnosis of PTCL, including the following categories: PTCL-U
           (peripheral T-cell lymphoma, unspecified), AILD-T (angioimmunoblastic-like T-cell
           lymphoma), ALKneg ALCL (ALK-negative anaplastic large cell lymphoma), intestinal T - NHL

        -  Advanced-stage disease (stage II-IV) or stage I and aaIPI score ≥ 2

        -  Informed written consent

      In clinical study A (Clin A) we are planning to evaluate the efficacy and the feasibility of
      an intensified chemo-immunotherapy program including auto-SCT or RIC allo-SCT in advanced
      stage PTCL pts ≥ 18 and < or = 60 years.

      In clinical study B (Clin B) we intend to verify the efficacy and the feasibility of a
      combined immuno-chemotherapy approach in a subset of elderly pts aged > 60 and < or = 75
      years.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Efficacy
time frame: one year
description: number of clinical responses
measure: evaluation of OS (overall survival)
time frame: 4 years
description: OS time is calculated from patients enrollment to death for all causes; censored cases are pts alive at the date of last follow-up assessment.
measure: DFS (Disease Free Survival)
time frame: 4 years
description: DFS time is the interval between CR achievement and the first disease relapse or death regardless of the cause.Definition of disease response/progression will be performed according to the criteria published by Juweid et al.(J Clin Oncol. 2005; 23: 4652-61)
measure: TRM (Treatment Related Mortality)
time frame: 4 years
description: TRM will be analysed by computing the corresponding crude cumulative incidence curve, considering disease-related death as competing event.
arm group label: Clin A
arm group type: Experimental
description: Clin A. CHOP-Campath (CHOP-C) for 2 cycles , Hyper-C-Hidam for 2 cycles and auto-SCT (stem cell transplantation) or RIC allo-SCT in advanced stage PTCL pts ≥ 18 and ≤ 60 years
arm group label: Clin B
arm group type: Experimental
description: Clin B: CHOP-Campath (CHOP-C) for 6 cycles . It is a combined immunochemotherapy approach in a subset of elderly pts aged > 60 ≤ 75 years
intervention type: Procedure
intervention name: Clin A. CHOP-CAMPATH (Chemo-immunotherapy) + SCT
description: Clin A:
CHOP-Campath (CHOP-C) for 2 cycles (every 21 days): Doxorubicin 50mg/m2 day +1, Vincristin 1.4mg/m2 day +1, Cyclophosphamide 750mg/m2 day +1, prednisone 100mg/m2 PO on days +1 to +5; Campath-1H (alemtuzumab) dose escalation 3-10-20mg IV days - 2, - 1, 0 (first CHOP-C) or 30mg SC day 0 (second CHOP-C). Methotrexate 12.5mg IT, Ara-C 40mg IT, Dexamethasone 4mg IT on days + 1 and 21 (first and second CHOP-C).
HYPER-C-HiDAM for 2 cycles: Methotrexate 1.5gr/m2 day +1; Cyclophosphamide 300mg/m2 every 12 hours days +2-3-4; ARA-C 2gr/m2 every 12 hours days +2-3-4; G-CSF 5μcg/kg/day starting from day +5 until peripheral blood stem cell harvest
Myeloablative regimen followed by autologous transplantation or Reduced intensity conditioning followed by allogeneic transplantation.
arm group label: Clin A
other name: Mab - Campath (Alemtuzumab)
intervention type: Drug
intervention name: Clin B (CHOP- CAMPATH) Chemo-immunotherapy
description: Clin B:
CHOP-Campath (CHOP-C) for 6 cycles (every 21 days): Doxorubicin 50mg/m2 day +1, Vincristin 1.4mg/m2 day +1, Cyclophosphamide 750mg/m2 day +1, prednisone 100mg/m2 PO from day +1 to day +5¸ Campath-1H (alemtuzumab) 3-10mg IV on days - 1 and 0 ( first CHOP-C course) or 10mg SC on day 0 (for the following 5 C-CHOP courses). Methotrexate 12.5mg IT, Ara-C 40mg IT, Dexamethasone 4mg IT on day +1 of each CHOP-C course.
arm group label: Clin B
other name: Mab- Campath (Alemtuzumab)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: paolo corradini
role: Principal Investigator
affiliation: fondazione IRCCS istituto nazionale tumori Milano
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
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facility: 
facility: 
facility: 
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country: Italy
responsible party type: Principal Investigator
investigator affiliation: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
investigator full name: Paolo Corradini
investigator title: Director Hematology and BMT Unit
mesh term: Lymphoma
mesh term: Lymphoma, T-Cell
mesh term: Lymphoma, T-Cell, Peripheral
mesh term: Alemtuzumab
mesh term: Immunomodulating Agents
mesh term: Immunologic Factors