<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/NCT01662050</url>
  </required_header>
  <id_info>
    <org_study_id>FIL-RBAC500</org_study_id>
    <nct_id>NCT01662050</nct_id>
  </id_info>
  <brief_title>Phase II Study of Age-Adjusted Rituximab, Bendamustine, Cytarabine as Induction Therapy in Older Patients With MCL</brief_title>
  <acronym>FIL-RBAC500</acronym>
  <official_title>Phase II Study of Age-Adjusted R-BAC (Rituximab, Bendamustine, Cytarabine) as Induction Therapy in Older Patients With Mantle Cell Lymphoma (MCL)</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>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      A phase 2 study of standard R-BAC (rituximab 375 mg/m2, bendamustine 70 mg/m2, ara-c 800&#xD;
      mg/m2) has been recently ultimated at the Vicenza Hematology Department involving several&#xD;
      regional centers on both untreated and previously treated patients with Mantle Cell Lymphoma&#xD;
      (MCL). An interim analysis conducted on 30 patients showed that rituximab + bendamustine +&#xD;
      ara-c combination had very good clinical activity, but a quite relevant hematological&#xD;
      toxicity, especially in previously treated and older patients (Visco C, ICML 2011 Lugano&#xD;
      Conference, Poster 236).&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
      The primary objective is to determine the activity (complete remission rate according to&#xD;
      Cheson 2007 criteria) and safety of age-adjusted Rituximab-Bendamustine-Cytarabine (RBAC500)&#xD;
      regimen at the end of treatment in older untreated patients with MCL.&#xD;
&#xD;
      The secondary objectives are to determine:&#xD;
&#xD;
        -  The rate of molecular response (characterized by labs of the FIL)&#xD;
&#xD;
        -  The progression-free survival (PFS)&#xD;
&#xD;
        -  The overall survival (OS)&#xD;
&#xD;
        -  The duration of responses (DOR)&#xD;
&#xD;
        -  The rate of patients that complete the expected treatment schedule (6 courses)&#xD;
&#xD;
        -  The rate of patients that are subject to dose reductions or delays&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study End points Primary efficacy end point of the study is the proportion of CR defined&#xD;
      according to Cheson criteria (2007) at the end of treatment (6 or 4 cycles). Primary safety&#xD;
      end point is the occurrence of any of the stop treatment criteria or of any episode of&#xD;
      relevant toxicity, as above defined.&#xD;
&#xD;
      Secondary end points are MRD defined response, OS, PFS and DOR (Cheson 2007). Molecular&#xD;
      response is the proportion of patients with molecular rearrangements at baseline that become&#xD;
      negative during treatment, measured by qualitative and quantitative PCR.&#xD;
&#xD;
      OS is measured from enrollment until death from any cause. PFS is measured from the time of&#xD;
      enrollment until disease progression, relapse or death from any cause. DOR is measured from&#xD;
      the first assessment that documents response (CR or PR) to the date of disease relapse or&#xD;
      progression. Minimum follow up required for all patients will be 24 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 20, 2012</start_date>
  <completion_date type="Actual">September 11, 2017</completion_date>
  <primary_completion_date type="Actual">August 2014</primary_completion_date>
  <phase>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>complete remission rate at the end of treatment</measure>
    <time_frame>6 months</time_frame>
    <description>The primary objective is to determine the activity [complete remission rate (CR) according to Cheson 2007 criteria]</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Toxicity will be represented by the occurrence of any of the stop treatment criteria or of any episode of relevant toxicity</measure>
    <time_frame>6 months</time_frame>
    <description>Relevant toxicity:&#xD;
Grade 4 cytopenia lasting for more than 6 days or Grade 3-4 non-hematologic toxicity or Febrile neutropenia lasting for more than 3 consecutive days.&#xD;
Stop treatment criteria:&#xD;
Occurrence of relevant toxicity for two subsequent or consecutive cycles.&#xD;
Grade 3-4 hematological or non-hematological toxicity on day +28 of a cycle not resolving within two weeks.&#xD;
Grade 3-4 hematological or non-hematological toxicity on day +28 of a cycle after 25% dose reduction.&#xD;
Patient refusal to procede with further cycles due to perceived excessive toxicity.&#xD;
Any unpredictable drug related event that suggests against study continuation</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>the rate of molecular response</measure>
    <time_frame>6 months</time_frame>
    <description>the rate of molecular response (characterized by labs of the FIL)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>the progression-free survival (PFS)</measure>
    <time_frame>30 months</time_frame>
    <description>the progression-free survival (PFS)is defined as the time from enrollment to complete remission with disappearance of all evidence of disease, disease progression or relapse or death from any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>the overall survival (OS)</measure>
    <time_frame>30 months</time_frame>
    <description>the overall survival (OS) is defined as the time from enrollment to death from any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>the duration of responses (DOR)</measure>
    <time_frame>30 months</time_frame>
    <description>the duration of responses (DOR)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>the rate of completion of treatment</measure>
    <time_frame>6 months</time_frame>
    <description>the rate of patients that complete the expected treatment schedule (6 courses)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>the rate of dose reductions or delays</measure>
    <time_frame>6 months</time_frame>
    <description>the rate of patients that are subject to dose reductions or delays</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">57</enrollment>
  <condition>Mantle Cell Lymphoma</condition>
  <arm_group>
    <arm_group_label>One arm for all patients.</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Rituximab, Bendamustine, Cytarabine</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rituximab, Bendamustine, Cytarabine.</intervention_name>
    <description>6 cycles of 28 days with Rituximab, Bendamustine and Cytarabine (R-BAC). Rituximab 375mg/mq; Bendamustine 70mg/mq; Cytarabine 500mg/mq.</description>
    <arm_group_label>One arm for all patients.</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Previously untreated patients with MCL aged &gt; 65 years if they are FIT according to&#xD;
             the geriatric CGA assessment.&#xD;
&#xD;
          -  age 60-65 years not eligible to high-dose chemotherapy plus transplantation, FIT or&#xD;
             UNFIT according to the geriatric CGA assessment.&#xD;
&#xD;
          -  ECOG performance status ≤ 2.&#xD;
&#xD;
          -  Positivity for cyclin D1 and SOX11 [the latter being mandatory in cases lacking cyclin&#xD;
             D1- or t(11;14)-negative], CD20 and CD5.&#xD;
&#xD;
          -  Adequate renal function (Creatinine clearance &gt; 40 mL/min), with preserved diuresis.&#xD;
&#xD;
          -  Adequate liver function: alanine aminotransferase (ALT)/aspartate aminotransferase&#xD;
             (AST) &lt; 2.5 x upper limit of normal (ULN) value, total bilirubin &lt; 2 mg/dL, unless&#xD;
             directly attributable to the patient's tumor.&#xD;
&#xD;
          -  Hepatitis B core antibody (HBcAb) positive/HBsAg negative/HBV-DNA negative patients&#xD;
             may be enrolled if correct antiviral prophylaxis is administered at least 2 weeks&#xD;
             before initiating protocol treatment.&#xD;
&#xD;
          -  Written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Human immunodeficiency virus (HIV) positive.&#xD;
&#xD;
          -  Previous treatment for lymphoma&#xD;
&#xD;
          -  Medical conditions or organ injuries that could interfere with administration of&#xD;
             therapy.&#xD;
&#xD;
          -  Active bacterial, viral, or fungal infection requiring systemic therapy.&#xD;
&#xD;
          -  Seizure disorders requiring anticonvulsant therapy.&#xD;
&#xD;
          -  Severe chronic obstructive pulmonary disease with hypoxemia.&#xD;
&#xD;
          -  History of severe cardiac disease: New York Heart Association (NYHA) functional class&#xD;
             III-IV, myocardial infarction within 6 months, ventricular tachyarrhythmias,&#xD;
             dilatative cardiomyopathy, or unstable angina.&#xD;
&#xD;
          -  Uncontrolled diabetes mellitus.&#xD;
&#xD;
          -  Active secondary malignancy.&#xD;
&#xD;
          -  Known hypersensitivity or anaphylactic reactions to murine antibodies and proteins, to&#xD;
             Bendamustine or mannitol.&#xD;
&#xD;
          -  Major surgery within 4 weeks of study Day 1.&#xD;
&#xD;
          -  HBsAg+&#xD;
&#xD;
          -  HCVAb+ patients with active viral replication (HCV-RNA+ with AST &gt; 2 x normal limit)&#xD;
&#xD;
          -  Any co-existing medical or psychological condition that would preclude participation&#xD;
             in the study or compromise the patient's ability to give informed consent, or that may&#xD;
             affect the interpretation of the results, or render the patient at high risk from&#xD;
             treatment complications.&#xD;
&#xD;
          -  CNS involvement (a diagnostic lumbar puncture will be performed in patients with the&#xD;
             blastoid variant of MCL)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>65 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Carlo Visco, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ospedale ULSS 6 di Vicenza - Ematologia</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>A.O. Policlinico Consorziale</name>
      <address>
        <city>Bari</city>
        <state>BA</state>
        <zip>70124</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IRCCS Ospedale Oncologico</name>
      <address>
        <city>Bari</city>
        <state>BA</state>
        <zip>70124</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>A.O. Spedali Civili</name>
      <address>
        <city>Brescia</city>
        <state>BS</state>
        <zip>25100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>U.O.C. Ematologia Ospedale &quot;San Nicola Pellegrino&quot; ASL BAT</name>
      <address>
        <city>Trani</city>
        <state>BT</state>
        <zip>70031</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>AO Valduce</name>
      <address>
        <city>Como</city>
        <state>CO</state>
        <zip>22100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>U.O.C. Garibaldi Nesima</name>
      <address>
        <city>Catania</city>
        <state>CT</state>
        <zip>95125</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AOU Careggi</name>
      <address>
        <city>Firenze</city>
        <state>FI</state>
        <zip>50134</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>A.O.U. San Martino</name>
      <address>
        <city>Genova</city>
        <state>GE</state>
        <zip>16132</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>PO Vito Fazzi</name>
      <address>
        <city>Lecce</city>
        <state>LE</state>
        <zip>73100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale Cardinale G. Panico</name>
      <address>
        <city>Tricase</city>
        <state>LE</state>
        <zip>73039</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Asur - Zona Territoriale 8</name>
      <address>
        <city>Civitanova Marche</city>
        <state>MC</state>
        <zip>62012</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>U.O.C. Ematologia - Policlinico Universitario</name>
      <address>
        <city>Messina</city>
        <state>ME</state>
        <zip>98100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico</name>
      <address>
        <city>Milano</city>
        <state>MI</state>
        <zip>20122</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>A.O. S. Carlo Borromeo di Milano Unità Semplice di Trapianto Midollo - A.O.S.Carlo Borromeo</name>
      <address>
        <city>Milano</city>
        <state>MI</state>
        <zip>20153</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>A.O. Niguarda</name>
      <address>
        <city>Milano</city>
        <state>MI</state>
        <zip>20162</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Osp. San Gerardo</name>
      <address>
        <city>Monza</city>
        <state>MI</state>
        <zip>20052</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Clinico Humanitas</name>
      <address>
        <city>Rozzano</city>
        <state>MI</state>
        <zip>20089</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Oncologico Modenese (COM)</name>
      <address>
        <city>Modena</city>
        <state>MO</state>
        <zip>41100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>&quot;La Maddalena&quot;</name>
      <address>
        <city>Palermo</city>
        <state>PA</state>
        <zip>90146</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedali Riuniti Villa Sofia - Cervello</name>
      <address>
        <city>Palermo</city>
        <state>PA</state>
        <zip>90146</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale Civile Guglielmo da Saliceto</name>
      <address>
        <city>Piacenza</city>
        <state>PC</state>
        <zip>29121</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Università di Padova</name>
      <address>
        <city>Padova</city>
        <state>PD</state>
        <zip>35128</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Presidio ospedaliero di Pescara</name>
      <address>
        <city>Pescara</city>
        <state>PE</state>
        <zip>65124</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CRO Aviano</name>
      <address>
        <city>Aviano</city>
        <state>PN</state>
        <zip>33081</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>Osp. S. Maria delle Croci</name>
      <address>
        <city>Ravenna</city>
        <state>RA</state>
        <zip>48121</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera &quot;Bianchi Melacrino Morelli&quot;</name>
      <address>
        <city>Reggio Calabria</city>
        <state>RC</state>
        <zip>89125</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Arcispedale &quot;S.Maria Nuova&quot;</name>
      <address>
        <city>Reggio Emilia</city>
        <state>RE</state>
        <zip>42100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>A.O. San Camillo Forlanini</name>
      <address>
        <city>Roma</city>
        <state>RM</state>
        <zip>00152</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nuovo Regina Margherita</name>
      <address>
        <city>Roma</city>
        <state>RM</state>
        <zip>00153</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Università &quot;La Sapienza&quot;</name>
      <address>
        <city>Roma</city>
        <state>RM</state>
        <zip>00161</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>A.O. S. Giovanni Addolorata</name>
      <address>
        <city>Roma</city>
        <state>RM</state>
        <zip>00184</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale degli Infermi di Rimini</name>
      <address>
        <city>Rimini</city>
        <state>RN</state>
        <zip>47900</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda ULSS 18</name>
      <address>
        <city>Rovigo</city>
        <state>RO</state>
        <zip>45100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Osp. Umberto I</name>
      <address>
        <city>Nocera Inferiore</city>
        <state>SA</state>
        <zip>84014</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>A.O.U. San Giovanni di Dio e Ruggi d'Aragona</name>
      <address>
        <city>Salerno</city>
        <state>SA</state>
        <zip>84131</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Az. Ospedaliera Univ. Senese</name>
      <address>
        <city>Siena</city>
        <state>SI</state>
        <zip>53100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ASL TO4</name>
      <address>
        <city>Ciriè-Ivrea-Chivasso</city>
        <state>TO</state>
        <zip>10043</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale S. Luigi Gonzaga,</name>
      <address>
        <city>Orbassano</city>
        <state>TO</state>
        <zip>10043</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>A.O.U. S. Giovanni Battista -Ematologia 2</name>
      <address>
        <city>Torino</city>
        <state>TO</state>
        <zip>10126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AOU San Giovanni Battista-Ematologia 1</name>
      <address>
        <city>Torino</city>
        <state>TO</state>
        <zip>10126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>A.O. S. Maria di Terni</name>
      <address>
        <city>Terni</city>
        <state>TR</state>
        <zip>05100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliero - Universitaria di Udine</name>
      <address>
        <city>Udine</city>
        <state>UD</state>
        <zip>33100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale di Circolo e Fondazione Macchi - Ematologia</name>
      <address>
        <city>Varese</city>
        <state>VA</state>
        <zip>21100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale di Circolo e Fondazione Macchi - Oncologia</name>
      <address>
        <city>Varese</city>
        <state>VA</state>
        <zip>21100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Osp. S. Andrea Vercelli</name>
      <address>
        <city>Vercelli</city>
        <state>VC</state>
        <zip>13100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale Civile di Mirano</name>
      <address>
        <city>Mirano</city>
        <state>VE</state>
        <zip>30035</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale San Bortolo</name>
      <address>
        <city>Vicenza</city>
        <state>VI</state>
        <zip>36100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale Policlinico G.B. Rossi (Borgo Roma) Di Verona</name>
      <address>
        <city>Verona</city>
        <state>VR</state>
        <zip>37126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>A.O. SS. Antonio e Biagio e C. Arrigo</name>
      <address>
        <city>Alessandria</city>
        <zip>15121</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Comprensorio sanitario di Bolzano</name>
      <address>
        <city>Bolzano</city>
        <zip>39100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale Cardarelli</name>
      <address>
        <city>Campobasso</city>
        <zip>86100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>A.O. Pugliese-Ciacci</name>
      <address>
        <city>Catanzaro</city>
        <zip>88100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IRST</name>
      <address>
        <city>Meldola</city>
        <zip>47014</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Università del Piemonte Orientale - Novara</name>
      <address>
        <city>Novara</city>
        <zip>28100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>June 26, 2012</study_first_submitted>
  <study_first_submitted_qc>August 7, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 10, 2012</study_first_posted>
  <last_update_submitted>August 8, 2022</last_update_submitted>
  <last_update_submitted_qc>August 8, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 9, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>MCL</keyword>
  <keyword>Mantle Cell Lymphoma</keyword>
  <keyword>Older</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, Mantle-Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cytarabine</mesh_term>
    <mesh_term>Rituximab</mesh_term>
    <mesh_term>Bendamustine Hydrochloride</mesh_term>
  </intervention_browse>
  <pending_results>
    <submitted>August 11, 2022</submitted>
    <returned>July 12, 2023</returned>
  </pending_results>
  <!-- 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/NCT01662050
org study id: FIL-RBAC500
nct id: NCT01662050
lead sponsor: 
has dmc: No
A phase 2 study of standard R-BAC (rituximab 375 mg/m2, bendamustine 70 mg/m2, ara-c 800
      mg/m2) has been recently ultimated at the Vicenza Hematology Department involving several
      regional centers on both untreated and previously treated patients with Mantle Cell Lymphoma
      (MCL). An interim analysis conducted on 30 patients showed that rituximab + bendamustine +
      ara-c combination had very good clinical activity, but a quite relevant hematological
      toxicity, especially in previously treated and older patients (Visco C, ICML 2011 Lugano
      Conference, Poster 236).

      Objectives:

      The primary objective is to determine the activity (complete remission rate according to
      Cheson 2007 criteria) and safety of age-adjusted Rituximab-Bendamustine-Cytarabine (RBAC500)
      regimen at the end of treatment in older untreated patients with MCL.

      The secondary objectives are to determine:

        -  The rate of molecular response (characterized by labs of the FIL)

        -  The progression-free survival (PFS)

        -  The overall survival (OS)

        -  The duration of responses (DOR)

        -  The rate of patients that complete the expected treatment schedule (6 courses)

        -  The rate of patients that are subject to dose reductions or delays
Study End points Primary efficacy end point of the study is the proportion of CR defined
      according to Cheson criteria (2007) at the end of treatment (6 or 4 cycles). Primary safety
      end point is the occurrence of any of the stop treatment criteria or of any episode of
      relevant toxicity, as above defined.

      Secondary end points are MRD defined response, OS, PFS and DOR (Cheson 2007). Molecular
      response is the proportion of patients with molecular rearrangements at baseline that become
      negative during treatment, measured by qualitative and quantitative PCR.

      OS is measured from enrollment until death from any cause. PFS is measured from the time of
      enrollment until disease progression, relapse or death from any cause. DOR is measured from
      the first assessment that documents response (CR or PR) to the date of disease relapse or
      progression. Minimum follow up required for all patients will be 24 months.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: complete remission rate at the end of treatment
time frame: 6 months
description: The primary objective is to determine the activity [complete remission rate (CR) according to Cheson 2007 criteria]
measure: Toxicity will be represented by the occurrence of any of the stop treatment criteria or of any episode of relevant toxicity
time frame: 6 months
description: Relevant toxicity:
Grade 4 cytopenia lasting for more than 6 days or Grade 3-4 non-hematologic toxicity or Febrile neutropenia lasting for more than 3 consecutive days.
Stop treatment criteria:
Occurrence of relevant toxicity for two subsequent or consecutive cycles.
Grade 3-4 hematological or non-hematological toxicity on day +28 of a cycle not resolving within two weeks.
Grade 3-4 hematological or non-hematological toxicity on day +28 of a cycle after 25% dose reduction.
Patient refusal to procede with further cycles due to perceived excessive toxicity.
Any unpredictable drug related event that suggests against study continuation
measure: the rate of molecular response
time frame: 6 months
description: the rate of molecular response (characterized by labs of the FIL)
measure: the progression-free survival (PFS)
time frame: 30 months
description: the progression-free survival (PFS)is defined as the time from enrollment to complete remission with disappearance of all evidence of disease, disease progression or relapse or death from any cause.
measure: the overall survival (OS)
time frame: 30 months
description: the overall survival (OS) is defined as the time from enrollment to death from any cause
measure: the duration of responses (DOR)
time frame: 30 months
description: the duration of responses (DOR)
measure: the rate of completion of treatment
time frame: 6 months
description: the rate of patients that complete the expected treatment schedule (6 courses)
measure: the rate of dose reductions or delays
time frame: 6 months
description: the rate of patients that are subject to dose reductions or delays
arm group label: One arm for all patients.
arm group type: Experimental
description: Rituximab, Bendamustine, Cytarabine
intervention type: Drug
intervention name: Rituximab, Bendamustine, Cytarabine.
description: 6 cycles of 28 days with Rituximab, Bendamustine and Cytarabine (R-BAC). Rituximab 375mg/mq; Bendamustine 70mg/mq; Cytarabine 500mg/mq.
arm group label: One arm for all patients.
criteria: 
gender: All
minimum age: 65 Years
maximum age: N/A
healthy volunteers: No
last name: Carlo Visco, MD
role: Principal Investigator
affiliation: Ospedale ULSS 6 di Vicenza - Ematologia
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country: Italy
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, Mantle-Cell
mesh term: Cytarabine
mesh term: Rituximab
mesh term: Bendamustine Hydrochloride
submitted: August 11, 2022
returned: July 12, 2023