<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/NCT02223208</url>
  </required_header>
  <id_info>
    <org_study_id>FIL_PTCL13</org_study_id>
    <nct_id>NCT02223208</nct_id>
  </id_info>
  <brief_title>Ro Plus CHOEP as First Line Treatment Before HSCT in Young Patients With Nodal Peripheral T-cell Lymphomas</brief_title>
  <acronym>FIL_PTCL13</acronym>
  <official_title>Romidepsin in Combination With CHOEP as First Line Treatment Before Hematopoietic Stem Cell Transplantation in Young Patients With Nodal Peripheral T-cell Lymphomas: a Phase I-II Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fondazione Italiana Linfomi - ETS</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fondazione Italiana Linfomi - ETS</source>
  <brief_summary>
    <textblock>
      This is a multicenter study that includes two phases:&#xD;
&#xD;
        1. A phase I study to define the maximum tolerated dose (MTD) of Romidepsin in addition to&#xD;
           CHOEP-21 and to test the safety and feasibility of CHOEP-21 in combination with dose&#xD;
           escalation of Romidepsin (8, 10, 12, 14 mg). The dose level defined as MTD of Romidepsin&#xD;
           will be used for the subsequent phase II study.&#xD;
&#xD;
        2. A phase II study to evaluate the efficacy (response rate, progression free survival and&#xD;
           overall survival) and safety of Ro-CHOEP-21 incorporated into a treatment strategy&#xD;
           including SCT.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PHASE I A1) Induction phase Ro-CHOEP-21 x 3 cycles&#xD;
&#xD;
        -  Romidepsin (dose escalation) starting dose: 12mg/ms iv day +1 and +8. Dose modification&#xD;
           according to toxicity (14mg/ms day +1 and +8; 10mg/ms day +1 and +8; 8mg/ms day +1 and&#xD;
           +8);&#xD;
&#xD;
        -  CHOEP-21 (Doxorubicin 50 mg/ms iv day +1; Vincristin 1.4 mg/ms (maximum 2.0 mg total&#xD;
           dose) iv day+1; Cyclophosphamide 750 mg/ms iv day +1; Etoposide 100mg/ms iv from day +1&#xD;
           to +3; Prednisone100 mg orally from days +1 to +5).&#xD;
&#xD;
      According to the response achieved after the first 3 Ro-CHOEP-21 cycles:&#xD;
&#xD;
        -  PR or CR: Ro-CHOEP-21 for 3 additional cycles followed by phase A2&#xD;
&#xD;
        -  SD or PD: Treatment failures, proceed to salvage according to each institutional policy.&#xD;
&#xD;
      A2) Stem cell mobilization and transplantation phase Response evaluation and one DHAP course&#xD;
      followed by peripheral stem cell harvesting.&#xD;
&#xD;
      According to response achieved after 6 Ro-CHOEP-21 cycles:&#xD;
&#xD;
      CR: BEAM or FEAM or CEAM followed by auto-SCT PR&#xD;
&#xD;
        -  Allogeneic SCT with HLA-identical (A, B, C, DR, DQ loci) or one antigen mismatched&#xD;
           (class I) sibling donors. Donor selection is based on molecular high-resolution typing&#xD;
           (4 digits) of the HLA gene loci class I (HLA-A, B, and C) and class II (DRB1, DQB1). In&#xD;
           case, no class I and class II completely identical urelated donor (10 out of 10 gene&#xD;
           loci) can be identified, the degree of histocompatibility between patient and donor must&#xD;
           fulfill with the minimal degree of matching established by the Italian Bone Marrow Donor&#xD;
           Registry: HLA-A and HLA-B antigen histocompatibility and HLA-DRB1 allelic&#xD;
           histocompatibility.&#xD;
&#xD;
        -  when a suitable donor is not available: BEAM or FEAM or CEAM followed by Auto-SCT.&#xD;
&#xD;
        -  Haploidentical transplantation is allowed in selected cases &lt; PR: Treatment failures,&#xD;
           proceed to salvage according to each institutional policy.&#xD;
&#xD;
      PHASE II A1) Induction phase Ro-CHOEP-21 x 3 cycles&#xD;
&#xD;
        -  Romidepsin dose according to phase I iv day +1 and +8&#xD;
&#xD;
        -  Doxorubicin 50 mg/ms iv day +1,&#xD;
&#xD;
        -  Vincristin 1.4 mg/ms (maximum 2.0 mg total dose) iv day+1,&#xD;
&#xD;
        -  Cyclophosphamide 750 mg/ms iv day +1,&#xD;
&#xD;
        -  Etoposide 100mg/ms iv from day +1 to +3&#xD;
&#xD;
        -  Prednisone100 mg orally from days +1 to +5&#xD;
&#xD;
      According to the response achieved after the first 3 Ro-CHOEP-21 cycles:&#xD;
&#xD;
        -  PR or CR: Ro-CHOEP-21 for 3 additional cycles followed by phase A2&#xD;
&#xD;
        -  SD or PD: Treatment failures, proceed to salvage according to each institutional policy.&#xD;
&#xD;
      A2) Stem cell mobilization and transplantation phase Response evaluation and one DHAP course&#xD;
      followed by peripheral stem cell harvesting.&#xD;
&#xD;
      According to response achieved after 6 Ro-CHOEP-21 cycles:&#xD;
&#xD;
      CR: BEAM or FEAM or CEAM followed by auto-SCT PR&#xD;
&#xD;
        -  Allogeneic SCT with HLA-identical (A, B, C, DR, DQ loci) or one antigen mismatched&#xD;
           (class I) sibling donors. Donor selection is based on molecular high-resolution typing&#xD;
           (4 digits) of the HLA gene loci class I (HLA-A, B, and C) and class II (DRB1, DQB1). In&#xD;
           case, no class I and class II completely identical urelated donor (10 out of 10 gene&#xD;
           loci) can be identified, the degree of histocompatibility between patient and donor must&#xD;
           fulfill with the minimal degree of matching established by the Italian Bone Marrow Donor&#xD;
           Registry: HLA-A and HLA-B antigen histocompatibility and HLA-DRB1 allelic&#xD;
           histocompatibility.&#xD;
&#xD;
        -  when a suitable donor is not available: BEAM or FEAM or CEAM followed by Auto-SCT.&#xD;
&#xD;
        -  Haploidentical transplantation is allowed in selected cases &lt; PR: Treatment failures,&#xD;
           proceed to salvage according to each institutional policy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">September 2014</start_date>
  <completion_date type="Anticipated">October 2026</completion_date>
  <primary_completion_date type="Actual">October 2020</primary_completion_date>
  <phase>Phase 1/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>Dose-limiting toxicity (DLT) of Ro-CHOEP-21 (Phase I endpoint)</measure>
    <time_frame>3 months</time_frame>
    <description>Incidence of dose-limiting toxicity (DLT) of Ro-CHOEP-21, considering as maximum dose the one causing induction of any grade ≥ 3 non hematologic toxicity or a delay &gt;15 days of planned cycle date observed during the first two cycles according to the definitions of NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 (2009)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Progression Free Survival (PFS) of Ro-CHOEP-21 (Phase II endpoint)</measure>
    <time_frame>18 months</time_frame>
    <description>PFS on intention to treatment (ITT) evaluated at 18 months. PFS will be defined as the time between the date of enrolment and the date of disease progression, relapse or death from any cause.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients reaching SCT (Phase I endpoint)</measure>
    <time_frame>6 months</time_frame>
    <description>Proportion of patients reaching SCT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ORR = Overall response rate (Phase I endpoint)</measure>
    <time_frame>6 months</time_frame>
    <description>Overall response rate (ORR, defined according to the Cheson 2007 response criteria) of the combination of Ro-CHOEP-21.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Response Rate (ORR) and Complete Response (CR)(Phase II endpoint)</measure>
    <time_frame>6 months</time_frame>
    <description>ORR and CR (defined according to the Cheson 2007 response criteria), after induction treatment and after SCT.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Event free survival (EFS) (Phase II endpoint)</measure>
    <time_frame>18 months</time_frame>
    <description>Event free survival (EFS) defined as the time between the date of enrollment and the date of discontinuation of treatment for any reason</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS) (Phase II endpoint)</measure>
    <time_frame>24 months</time_frame>
    <description>Overall survival (OS) defined as the time between the date of enrolment and the date of death from any cause in the ITT population enrolled in the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS) and Overall Survival (OS) (Phase II endpoint)</measure>
    <time_frame>3 months</time_frame>
    <description>PFS and OS in patients not responding to the first 3 courses of Ro-CHOEP-21</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Toxicities (Phase II endpoint)</measure>
    <time_frame>18 months</time_frame>
    <description>Evaluation during the interim analyses of any grade III or higher toxicities, recorded and classified according to the definitions of NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 (2009)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Higher toxicities (Phase II endpoint)</measure>
    <time_frame>18 months</time_frame>
    <description>Evaluation during all the pretransplant phase of any grade III or higher toxicities, recorded and classified according to the definitions of NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 (2009)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment-related mortality (TRM) (Phase II Endpoint)</measure>
    <time_frame>24 months</time_frame>
    <description>Treatment-related mortality defined as any death that was not attributable to the lymphoma.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Graft-versus-host disease (GVHD) (Phase II endpoint)</measure>
    <time_frame>24 months</time_frame>
    <description>Incidence of acute and chronic GVHD in allografted patients</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Evaluation of response biomarkers (eg TET2 mutations)</measure>
    <time_frame>8 years</time_frame>
    <description>Evaluation of response biomarkers (eg TET2 mutations)</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">89</enrollment>
  <condition>Peripheral T-cell Lymphomas (PTCL)</condition>
  <condition>PTCL-NOS</condition>
  <condition>Angioimmunoblastic T-cell Lymphoma (AITL)</condition>
  <condition>ALK- Anaplastic Large Cell Lymphoma (ALCL)</condition>
  <condition>Nodal Peripheral T-Cell Lymphoma of T Follicular Helper Cell Origin</condition>
  <arm_group>
    <arm_group_label>Ro-CHOEP-21</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>During the Phase I It will administered Romidepsin (dose escalation) and the combination of CHOEP-21. During the Phase II It will administered Romidepsin (dose according to phase I) and the combination of CHOEP-21.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ro-CHOEP-21 (PHASE I)</intervention_name>
    <description>Romidepsin (dose escalation) Starting dose: 12mg/ms iv day +1 and +8&#xD;
Dose modification according to toxicity:&#xD;
14mg/ms day +1 and +8&#xD;
10mg/ms day +1 and +8&#xD;
8mg/ms day +1 and +8&#xD;
CHOEP-21&#xD;
Doxorubicin 50 mg/ms iv day +1 or +2,&#xD;
Vincristin 1.4 mg/ms (maximum 2.0 mg total dose) iv day+1 or +2&#xD;
Cyclophosphamide 750 mg/ms iv day +1 or +2&#xD;
Etoposide 100mg/ms iv from day +1 to +3 or from day +2 to +4&#xD;
Prednisone100 mg orally from days +1 to +5 or from days +2 to +6&#xD;
PR or CR:Ro-CHOEP-21 for 3 additional cycles followed by stem cell mobilization and transplantation phase (CR --&gt; AUTO-SCT, PR --&gt; ALLO-SCT)</description>
    <arm_group_label>Ro-CHOEP-21</arm_group_label>
    <other_name>Romidepsin</other_name>
    <other_name>Cyclophosphamide</other_name>
    <other_name>Doxorubicin</other_name>
    <other_name>Vincristin</other_name>
    <other_name>Etoposide</other_name>
    <other_name>Prednisone</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ro-CHOEP-21 (PHASE II)</intervention_name>
    <description>Ro-CHOEP-21 x 3 cycles&#xD;
Romidepsin dose according to phase I iv day +1 and +8&#xD;
Doxorubicin 50 mg/ms iv day +1 or +2,&#xD;
Vincristin 1.4 mg/ms (maximum 2.0 mg total dose) iv day+1 or +2,&#xD;
Cyclophosphamide 750 mg/ms iv day +1 or +2&#xD;
Etoposide 100mg/ms iv from day +1 to +3 or from day +2 to +4&#xD;
Prednisone100 mg orally from days +1 to +5 or from days +2 to +6&#xD;
PR or CR: Ro-CHOEP-21 for 3 additional cycles followed by stem cell mobilization and transplantation phase (CR --&gt; AUTO-SCT, PR --&gt; ALLO-SCT)</description>
    <arm_group_label>Ro-CHOEP-21</arm_group_label>
    <other_name>Romidepsin</other_name>
    <other_name>Cyclophosphamide</other_name>
    <other_name>Doxorubicin</other_name>
    <other_name>Vincristin</other_name>
    <other_name>Etoposide</other_name>
    <other_name>Prednisone</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age ≥18 e ≤ 65 years&#xD;
&#xD;
          2. Peripheral T-cell lymphomas at diagnosis including: PTCL-NOS, AITL including other&#xD;
             nodal TFH, ALK-ALCL&#xD;
&#xD;
          3. Stage II-IV&#xD;
&#xD;
          4. Written informed consent&#xD;
&#xD;
          5. No prior treatment for lymphoma&#xD;
&#xD;
          6. No Central Nervous System (CNS) disease (meningeal and/or brain involvement by&#xD;
             lymphoma)&#xD;
&#xD;
          7. HIV negativity&#xD;
&#xD;
          8. Absence of active hepatitis C virus (HCV) infection&#xD;
&#xD;
          9. HBV negativity or patients with HBcAb +, HBsAg -, HBs Ab+/- with HBV-DNA negativity&#xD;
             (in these patients Lamivudine prophylaxis is mandatory)&#xD;
&#xD;
         10. Levels of serum bilirubin, alkaline phosphatase and transaminases &lt; 2 the upper normal&#xD;
             limit, if not disease related&#xD;
&#xD;
         11. No psychiatric illness that precludes understanding concepts of the trial or signing&#xD;
             informed consent&#xD;
&#xD;
         12. Ejection fraction &gt; 50% and myocardial stroke in the last year nor QT prolongation&#xD;
             (QTc interval &lt; 480 msec using the Fridericia formula)&#xD;
&#xD;
         13. Clearance of creatinine &gt; 60 ml/min if not disease related&#xD;
&#xD;
         14. Spirometry Diffusion Capacity (DLCO) &gt; 50%&#xD;
&#xD;
         15. Absence of active, uncontrolled infection&#xD;
&#xD;
         16. For males and females of child-bearing potential, agreement upon the use of effective&#xD;
             contraceptive methods prior to study entry, for the duration of study participation&#xD;
             and in the following 90 days after discontinuation of study treatment&#xD;
&#xD;
         17. Availability of histological material for central review and pathobiological studies.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Age &lt;18 e &gt; 65 years&#xD;
&#xD;
          2. Hystology other than: PTCL-NOS, AITL, ALK-ALCL&#xD;
&#xD;
          3. Stage I&#xD;
&#xD;
          4. Prior treatment for lymphoma&#xD;
&#xD;
          5. Positive serologic markers for human immunodeficiency virus (HIV)&#xD;
&#xD;
          6. Active hepatitis B virus (HBV) infection&#xD;
&#xD;
          7. Active hepatitis C virus (HCV) infection&#xD;
&#xD;
          8. Levels of serum bilirubin, alkaline phosphatase and transaminases &gt; 2 the upper normal&#xD;
             limit, if not disease related&#xD;
&#xD;
          9. Ejection fraction &lt; 50% and no myocardial stroke in the last year or QT prolongation&#xD;
             (QTc interval &gt; 480 msec using the Fridericia formula)&#xD;
&#xD;
         10. Clearance of creatinine &lt; 60 ml/min if not disease related&#xD;
&#xD;
         11. Spirometry Diffusion Capacity (DLCO) &lt; 50%&#xD;
&#xD;
         12. Pregnancy or lactation&#xD;
&#xD;
         13. Patient not agreeing to take adequate contraceptive measures during the study&#xD;
&#xD;
         14. Psychiatric disease that precludes understanding concepts of the trial or signing&#xD;
             informed consent&#xD;
&#xD;
         15. Any active, uncontrolled infection&#xD;
&#xD;
         16. Prior history of malignancies other than PTCLs in the last five years (except for&#xD;
             basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix&#xD;
             or breast).&#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>Paolo Corradini, Prof</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fondazione IRCCS Istituto Nazionale dei Tumori di Milano</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Ospedale SS. Antonio e Biagio e Cesare Arrigo</name>
      <address>
        <city>Alessandria</city>
        <state>AL</state>
        <zip>15121</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Policlinico S. Orsola Malpighi</name>
      <address>
        <city>Bologna</city>
        <state>BO</state>
        <zip>40138</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spedali Civili</name>
      <address>
        <city>Brescia</city>
        <state>BS</state>
        <zip>26123</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale Businco</name>
      <address>
        <city>Cagliari</city>
        <state>CA</state>
        <zip>09121</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera S.Croce e Carle</name>
      <address>
        <city>Cuneo</city>
        <state>CN</state>
        <zip>12100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.) - Sede di Meldola</name>
      <address>
        <city>Meldola</city>
        <state>FC</state>
        <zip>47014</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IRCCS AOU San Martino - Clinica Ematologica</name>
      <address>
        <city>Genova</city>
        <state>GE</state>
        <zip>16321</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IRCCS AOU San Martino - UO Ematologia 1</name>
      <address>
        <city>Genova</city>
        <state>GE</state>
        <zip>16321</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Clinico Humanitas</name>
      <address>
        <city>Rozzano</city>
        <state>Milano</state>
        <zip>20089</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico</name>
      <address>
        <city>Milano</city>
        <state>MI</state>
        <zip>20122</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione IRCCS &quot;Istituto Nazionale dei Tumori&quot;</name>
      <address>
        <city>Milano</city>
        <state>MI</state>
        <zip>20133</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Ospedale Niguarda Ca' Granda</name>
      <address>
        <city>Milano</city>
        <state>MI</state>
        <zip>20162</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AO Ospedali Riuniti Villa Sofia - Cervello (Presidio Cervello)</name>
      <address>
        <city>Palermo</city>
        <state>PA</state>
        <zip>90146</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IRCCS Centro di Riferimento Oncologico (CRO)</name>
      <address>
        <city>Aviano</city>
        <state>PN</state>
        <zip>33081</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AOU di Parma</name>
      <address>
        <city>Parma</city>
        <state>PR</state>
        <zip>43100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione IRCCS - Policlinico San Matteo</name>
      <address>
        <city>Pavia</city>
        <state>PV</state>
        <zip>27100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IRCCS Arcispedale &quot;Santa Maria Nuova&quot;</name>
      <address>
        <city>Reggio Emilia</city>
        <state>RE</state>
        <zip>42123</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale degli Infermi</name>
      <address>
        <city>Rimini</city>
        <state>RN</state>
        <zip>47900</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AO Città della Salute e della Scienza - Ematologia 1U</name>
      <address>
        <city>Torino</city>
        <state>TO</state>
        <zip>10126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AO Città della Salute e della Scienza - SC Ematologia</name>
      <address>
        <city>Torino</city>
        <state>TO</state>
        <zip>10126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AOU &quot;Santa Maria della Misericordia&quot;</name>
      <address>
        <city>Udine</city>
        <state>UD</state>
        <zip>33100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale Borgo Roma</name>
      <address>
        <city>Verona</city>
        <state>VR</state>
        <zip>37134</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Nazionale Tumori IRCCS - Fondazione G. Pascale</name>
      <address>
        <city>Napoli</city>
        <zip>80131</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale Maggiore della Carità - SCDU Ematologia</name>
      <address>
        <city>Novara</city>
        <zip>28100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>A.O. di Perugia - Santa Maria della Misericordia</name>
      <address>
        <city>Perugia</city>
        <zip>06132</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale G. Da Saliceto - AUSL di Piacenza</name>
      <address>
        <city>Piacenza</city>
        <zip>29121</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UO Ematologia Ospedale S.Maria delle Croci</name>
      <address>
        <city>Ravenna</city>
        <zip>48121</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>July 21, 2014</study_first_submitted>
  <study_first_submitted_qc>August 21, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 22, 2014</study_first_posted>
  <last_update_submitted>September 12, 2023</last_update_submitted>
  <last_update_submitted_qc>September 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>PTCL</keyword>
  <keyword>PTCL-NOS</keyword>
  <keyword>AITL</keyword>
  <keyword>ALCL</keyword>
  <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>
    <mesh_term>Lymphoma, Large-Cell, Anaplastic</mesh_term>
    <mesh_term>Immunoblastic Lymphadenopathy</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prednisone</mesh_term>
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Doxorubicin</mesh_term>
    <mesh_term>Liposomal doxorubicin</mesh_term>
    <mesh_term>Etoposide</mesh_term>
    <mesh_term>Etoposide phosphate</mesh_term>
    <mesh_term>Romidepsin</mesh_term>
    <mesh_term>Vincristine</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/NCT02223208
org study id: FIL_PTCL13
nct id: NCT02223208
lead sponsor: 
This is a multicenter study that includes two phases:

        1. A phase I study to define the maximum tolerated dose (MTD) of Romidepsin in addition to
           CHOEP-21 and to test the safety and feasibility of CHOEP-21 in combination with dose
           escalation of Romidepsin (8, 10, 12, 14 mg). The dose level defined as MTD of Romidepsin
           will be used for the subsequent phase II study.

        2. A phase II study to evaluate the efficacy (response rate, progression free survival and
           overall survival) and safety of Ro-CHOEP-21 incorporated into a treatment strategy
           including SCT.
PHASE I A1) Induction phase Ro-CHOEP-21 x 3 cycles

        -  Romidepsin (dose escalation) starting dose: 12mg/ms iv day +1 and +8. Dose modification
           according to toxicity (14mg/ms day +1 and +8; 10mg/ms day +1 and +8; 8mg/ms day +1 and
           +8);

        -  CHOEP-21 (Doxorubicin 50 mg/ms iv day +1; Vincristin 1.4 mg/ms (maximum 2.0 mg total
           dose) iv day+1; Cyclophosphamide 750 mg/ms iv day +1; Etoposide 100mg/ms iv from day +1
           to +3; Prednisone100 mg orally from days +1 to +5).

      According to the response achieved after the first 3 Ro-CHOEP-21 cycles:

        -  PR or CR: Ro-CHOEP-21 for 3 additional cycles followed by phase A2

        -  SD or PD: Treatment failures, proceed to salvage according to each institutional policy.

      A2) Stem cell mobilization and transplantation phase Response evaluation and one DHAP course
      followed by peripheral stem cell harvesting.

      According to response achieved after 6 Ro-CHOEP-21 cycles:

      CR: BEAM or FEAM or CEAM followed by auto-SCT PR

        -  Allogeneic SCT with HLA-identical (A, B, C, DR, DQ loci) or one antigen mismatched
           (class I) sibling donors. Donor selection is based on molecular high-resolution typing
           (4 digits) of the HLA gene loci class I (HLA-A, B, and C) and class II (DRB1, DQB1). In
           case, no class I and class II completely identical urelated donor (10 out of 10 gene
           loci) can be identified, the degree of histocompatibility between patient and donor must
           fulfill with the minimal degree of matching established by the Italian Bone Marrow Donor
           Registry: HLA-A and HLA-B antigen histocompatibility and HLA-DRB1 allelic
           histocompatibility.

        -  when a suitable donor is not available: BEAM or FEAM or CEAM followed by Auto-SCT.

        -  Haploidentical transplantation is allowed in selected cases < PR: Treatment failures,
           proceed to salvage according to each institutional policy.

      PHASE II A1) Induction phase Ro-CHOEP-21 x 3 cycles

        -  Romidepsin dose according to phase I iv day +1 and +8

        -  Doxorubicin 50 mg/ms iv day +1,

        -  Vincristin 1.4 mg/ms (maximum 2.0 mg total dose) iv day+1,

        -  Cyclophosphamide 750 mg/ms iv day +1,

        -  Etoposide 100mg/ms iv from day +1 to +3

        -  Prednisone100 mg orally from days +1 to +5

      According to the response achieved after the first 3 Ro-CHOEP-21 cycles:

        -  PR or CR: Ro-CHOEP-21 for 3 additional cycles followed by phase A2

        -  SD or PD: Treatment failures, proceed to salvage according to each institutional policy.

      A2) Stem cell mobilization and transplantation phase Response evaluation and one DHAP course
      followed by peripheral stem cell harvesting.

      According to response achieved after 6 Ro-CHOEP-21 cycles:

      CR: BEAM or FEAM or CEAM followed by auto-SCT PR

        -  Allogeneic SCT with HLA-identical (A, B, C, DR, DQ loci) or one antigen mismatched
           (class I) sibling donors. Donor selection is based on molecular high-resolution typing
           (4 digits) of the HLA gene loci class I (HLA-A, B, and C) and class II (DRB1, DQB1). In
           case, no class I and class II completely identical urelated donor (10 out of 10 gene
           loci) can be identified, the degree of histocompatibility between patient and donor must
           fulfill with the minimal degree of matching established by the Italian Bone Marrow Donor
           Registry: HLA-A and HLA-B antigen histocompatibility and HLA-DRB1 allelic
           histocompatibility.

        -  when a suitable donor is not available: BEAM or FEAM or CEAM followed by Auto-SCT.

        -  Haploidentical transplantation is allowed in selected cases < PR: Treatment failures,
           proceed to salvage according to each institutional policy.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Dose-limiting toxicity (DLT) of Ro-CHOEP-21 (Phase I endpoint)
time frame: 3 months
description: Incidence of dose-limiting toxicity (DLT) of Ro-CHOEP-21, considering as maximum dose the one causing induction of any grade ≥ 3 non hematologic toxicity or a delay >15 days of planned cycle date observed during the first two cycles according to the definitions of NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 (2009)
measure: Progression Free Survival (PFS) of Ro-CHOEP-21 (Phase II endpoint)
time frame: 18 months
description: PFS on intention to treatment (ITT) evaluated at 18 months. PFS will be defined as the time between the date of enrolment and the date of disease progression, relapse or death from any cause.
measure: Proportion of patients reaching SCT (Phase I endpoint)
time frame: 6 months
description: Proportion of patients reaching SCT
measure: ORR = Overall response rate (Phase I endpoint)
time frame: 6 months
description: Overall response rate (ORR, defined according to the Cheson 2007 response criteria) of the combination of Ro-CHOEP-21.
measure: Overall Response Rate (ORR) and Complete Response (CR)(Phase II endpoint)
time frame: 6 months
description: ORR and CR (defined according to the Cheson 2007 response criteria), after induction treatment and after SCT.
measure: Event free survival (EFS) (Phase II endpoint)
time frame: 18 months
description: Event free survival (EFS) defined as the time between the date of enrollment and the date of discontinuation of treatment for any reason
measure: Overall survival (OS) (Phase II endpoint)
time frame: 24 months
description: Overall survival (OS) defined as the time between the date of enrolment and the date of death from any cause in the ITT population enrolled in the study
measure: Progression Free Survival (PFS) and Overall Survival (OS) (Phase II endpoint)
time frame: 3 months
description: PFS and OS in patients not responding to the first 3 courses of Ro-CHOEP-21
measure: Toxicities (Phase II endpoint)
time frame: 18 months
description: Evaluation during the interim analyses of any grade III or higher toxicities, recorded and classified according to the definitions of NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 (2009)
measure: Higher toxicities (Phase II endpoint)
time frame: 18 months
description: Evaluation during all the pretransplant phase of any grade III or higher toxicities, recorded and classified according to the definitions of NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 (2009)
measure: Treatment-related mortality (TRM) (Phase II Endpoint)
time frame: 24 months
description: Treatment-related mortality defined as any death that was not attributable to the lymphoma.
measure: Graft-versus-host disease (GVHD) (Phase II endpoint)
time frame: 24 months
description: Incidence of acute and chronic GVHD in allografted patients
measure: Evaluation of response biomarkers (eg TET2 mutations)
time frame: 8 years
description: Evaluation of response biomarkers (eg TET2 mutations)
arm group label: Ro-CHOEP-21
arm group type: Experimental
description: During the Phase I It will administered Romidepsin (dose escalation) and the combination of CHOEP-21. During the Phase II It will administered Romidepsin (dose according to phase I) and the combination of CHOEP-21.
intervention type: Drug
intervention name: Ro-CHOEP-21 (PHASE I)
description: Romidepsin (dose escalation) Starting dose: 12mg/ms iv day +1 and +8
Dose modification according to toxicity:
14mg/ms day +1 and +8
10mg/ms day +1 and +8
8mg/ms day +1 and +8
CHOEP-21
Doxorubicin 50 mg/ms iv day +1 or +2,
Vincristin 1.4 mg/ms (maximum 2.0 mg total dose) iv day+1 or +2
Cyclophosphamide 750 mg/ms iv day +1 or +2
Etoposide 100mg/ms iv from day +1 to +3 or from day +2 to +4
Prednisone100 mg orally from days +1 to +5 or from days +2 to +6
PR or CR:Ro-CHOEP-21 for 3 additional cycles followed by stem cell mobilization and transplantation phase (CR --> AUTO-SCT, PR --> ALLO-SCT)
arm group label: Ro-CHOEP-21
other name: Romidepsin
other name: Cyclophosphamide
other name: Doxorubicin
other name: Vincristin
other name: Etoposide
other name: Prednisone
intervention type: Drug
intervention name: Ro-CHOEP-21 (PHASE II)
description: Ro-CHOEP-21 x 3 cycles
Romidepsin dose according to phase I iv day +1 and +8
Doxorubicin 50 mg/ms iv day +1 or +2,
Vincristin 1.4 mg/ms (maximum 2.0 mg total dose) iv day+1 or +2,
Cyclophosphamide 750 mg/ms iv day +1 or +2
Etoposide 100mg/ms iv from day +1 to +3 or from day +2 to +4
Prednisone100 mg orally from days +1 to +5 or from days +2 to +6
PR or CR: Ro-CHOEP-21 for 3 additional cycles followed by stem cell mobilization and transplantation phase (CR --> AUTO-SCT, PR --> ALLO-SCT)
arm group label: Ro-CHOEP-21
other name: Romidepsin
other name: Cyclophosphamide
other name: Doxorubicin
other name: Vincristin
other name: Etoposide
other name: Prednisone
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Paolo Corradini, Prof
role: Principal Investigator
affiliation: Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
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country: Italy
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, T-Cell
mesh term: Lymphoma, T-Cell, Peripheral
mesh term: Lymphoma, Large-Cell, Anaplastic
mesh term: Immunoblastic Lymphadenopathy
mesh term: Prednisone
mesh term: Cyclophosphamide
mesh term: Doxorubicin
mesh term: Liposomal doxorubicin
mesh term: Etoposide
mesh term: Etoposide phosphate
mesh term: Romidepsin
mesh term: Vincristine