<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/NCT04475731</url>
  </required_header>
  <id_info>
    <org_study_id>ALL2620</org_study_id>
    <nct_id>NCT04475731</nct_id>
  </id_info>
  <brief_title>Ponatinib in Adult Ph+ ALL Patients With MRD Positivity or Hematological Relapse</brief_title>
  <official_title>Ponatinib for the Management of Minimal Residual Disease (MRD) and Hematologic Relapse in Adult Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL) Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Gruppo Italiano Malattie EMatologiche dell'Adulto</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Gruppo Italiano Malattie EMatologiche dell'Adulto</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a phase II interventional trial to evaluate if the use of ponatinib, with or without&#xD;
      chemotherapy, can induce a molecular remission in MRD-positive patients, in patients in&#xD;
      hematologic and extra-hematologic relapse and in the few patients who never achieved an&#xD;
      hematologic remission after whatever prior treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a phase II interventional multicenter study for adult patients with Ph+ALL who:&#xD;
&#xD;
        -  Are MRD+ (i.e. BCR-ABL1/ABL1 &gt;0.01) (or loose their molecular response) after whichever&#xD;
           kind of previous treatment. MRD positivity is indeed regarded as a relapse/resistance,&#xD;
           since it represents the early recognition of cases who will eventually experience an&#xD;
           hematologic recurrence of disease.&#xD;
&#xD;
        -  Are in hematologic relapse after whichever kind of previous treatment.&#xD;
&#xD;
        -  Have never achieved an hematologic remission at least after one month of treatment.&#xD;
&#xD;
      Patients will be treated with Ponatinib at a dose of 45 mg/die per os for 28 days for 3&#xD;
      cycles and - if in hematologic and extra-hematologic relapse/refractoriness, clinically fit&#xD;
      and according to medical decision - with concurrent systemic chemotherapy. In case of CMR&#xD;
      achievement, dosing will be reduced to 30 mg. In case of toxicity, Ponatinib will be reduced&#xD;
      to 30 (or 15) mg daily.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">May 4, 2021</start_date>
  <completion_date type="Anticipated">November 2024</completion_date>
  <primary_completion_date type="Anticipated">November 2022</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>MRD negativity/reduction rate</measure>
    <time_frame>After 3 months of treatment</time_frame>
    <description>Rate of patients who achieve a MRD negativity/MRD reduction following treatment with either Ponatinib alone or in combination with systemic chemotherapy</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration of CMR</measure>
    <time_frame>at 24 months</time_frame>
    <description>Duration of the CMR status after 3 months of ponatinib treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hematologic remission rate</measure>
    <time_frame>at 24 months</time_frame>
    <description>The achievement of an hematologic remission in patients treated for an hematologic and extra-hematoloigc relapse and for a refractory disease.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Best molecular response</measure>
    <time_frame>at 24 months</time_frame>
    <description>Best molecular response achieved during the follow-up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of AE/SAEs</measure>
    <time_frame>at 24 months</time_frame>
    <description>Safety profile in terms of incidence of grade &gt;3 CTC-NCI side effects and toxicities (AE/SAEs).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mutational analysis</measure>
    <time_frame>at 24 months</time_frame>
    <description>Mutational analysis in terms of occurrence, type and number of BCR-ABL1 kinase domain mutations.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation between biological and MRD parameters</measure>
    <time_frame>at 24 months</time_frame>
    <description>Correlation between the achievement and duration of CMR (or MRD reduction) with the type of fusion protein (e.g. p190 or p210) and the potential occurrence of mutations, as well as with additional genomic lesions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease free survival</measure>
    <time_frame>24 months</time_frame>
    <description>Time interval between the achievement of CHR after three months of ponatinib and hematologic relapse of the disease or death in CHR; patients still alive, in CHR.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>24 months</time_frame>
    <description>Time interval between treatment start and death for any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative incidence of relapse</measure>
    <time_frame>24 months</time_frame>
    <description>Time interval between achievement of CHR after three months of ponatinib until the date of first hematologic relapse of the disease.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Role of hematological profile on survival outcome</measure>
    <time_frame>at 24 months</time_frame>
    <description>Identification of hematological profile on survival outcome</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">67</enrollment>
  <condition>Philadelphia-Positive ALL</condition>
  <condition>Acute Lymphoblastic Leukemia, in Relapse</condition>
  <arm_group>
    <arm_group_label>Experimental arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>MRD+ Ph+ ALL adult patients will receive Ponatinib x 4 weeks x 3 courses; +/-Concomitant chemotherapy (according to hematologic status).&#xD;
Patients will receive the study drug until disease relapse or progression.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ponatinib</intervention_name>
    <description>Ponatinib 45 mg/day x 4 weeks x 3 courses.&#xD;
+/- chemotherapy:&#xD;
vincristine or&#xD;
L-VAMP (leucovorin, vincristine, aracytin, methotrexate, prednisone)</description>
    <arm_group_label>Experimental arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Ph+ ALL patients with evidence of MRD disease or in hematologic and extra-hematologic&#xD;
             relapse/refractoriness after any previous treatment, will be considered eligible to&#xD;
             enter the study.&#xD;
&#xD;
          2. Age ≥18 years old with no upper age limit.&#xD;
&#xD;
          3. Adequate hepatic function as defined by the following criteria:&#xD;
&#xD;
               -  total serum bilirubin ≤1.5 x upper limit of normal (ULN), unless due to Gilbert's&#xD;
                  syndrome&#xD;
&#xD;
               -  alanine aminotransferase (ALT) ≤2.5 × ULN&#xD;
&#xD;
               -  aspartate aminotransferase (AST) ≤2.5 × ULN.&#xD;
&#xD;
          4. Adequate pancreatic function as defined by the following criterion:&#xD;
&#xD;
             - serum lipase and amylase ≤1.5 × ULN.&#xD;
&#xD;
          5. For females of childbearing potential, a negative pregnancy test must be documented&#xD;
             prior to enrollment.&#xD;
&#xD;
          6. Female and male patients who are fertile must agree to use an effective form of&#xD;
             contraception with their sexual partners from enrollment through 4 months after the&#xD;
             end of treatment.&#xD;
&#xD;
          7. Signed written informed consent according to ICH/EU/GCP and national local laws.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. WHO performance status ≤ 50% (Karnofsky) or ≥ 3 (ECOG).&#xD;
&#xD;
          2. Uncontrolled active HBV or HCV hepatitis, or AST/ALT ≥ 2.5 x ULN and bilirubine ≥ 1.5&#xD;
             x ULN not due to the disease.&#xD;
&#xD;
          3. History of acute pancreatitis within 1 year of study or history of chronic&#xD;
             pancreatitis.&#xD;
&#xD;
          4. History of alcohol abuse.&#xD;
&#xD;
          5. Ongoing or active uncontrolled infections.&#xD;
&#xD;
          6. Uncontrolled hypertriglyceridemia (triglycerides &gt;450 mg/dL).&#xD;
&#xD;
          7. Clinically significant, uncontrolled or active cardiovascular disease, specifically&#xD;
             including, but not restricted to:&#xD;
&#xD;
               -  any history of myocardial infarction, stroke, or revascularization&#xD;
&#xD;
               -  unstable angina or transient ischemic attack within 6 months prior to enrollment&#xD;
&#xD;
               -  congestive heart failure within 6 months prior to enrollment, or left ventricular&#xD;
                  ejection fraction (LVEF) less than lower limit of normal per local institutional&#xD;
                  standards within 6 months prior to enrollment&#xD;
&#xD;
               -  history of clinically significant (as determined by the treating physician)&#xD;
                  atrial arrhythmia&#xD;
&#xD;
               -  any history of ventricular arrhythmia&#xD;
&#xD;
               -  any history of venous thromboembolism including deep venous thrombosis or&#xD;
                  pulmonary embolism&#xD;
&#xD;
               -  uncontrolled hypertension (diastolic blood pressure &gt;90 mm Hg; systolic &gt;140 mm&#xD;
                  Hg). Patients with hypertension should be under treatment on study entry to&#xD;
                  effect blood pressure control.&#xD;
&#xD;
          8. Taking medications that are known to be associated with Torsades de Pointes.&#xD;
&#xD;
          9. Taking any medications or herbal supplements that are known to be strong inhibitors of&#xD;
             CYP3A4 within at least 14 days before the first dose of ponatinib.&#xD;
&#xD;
         10. Creatinine level &gt;2.5mg/dl or glomerular filtration rate (GFR) &lt;20 ml/min or&#xD;
             proteinuria &gt;3.5 g/day.&#xD;
&#xD;
         11. Patients who are currently receiving treatment with any of the medications listed in&#xD;
             Appendix E if the medications cannot be either discontinued or switched to a different&#xD;
             medication prior to starting study drug. The medications listed in Appendix E have the&#xD;
             potential to prolong QT.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Paola Fazi</last_name>
    <phone>0670390528</phone>
    <email>p.fazi@gimema.it</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Enrico Crea</last_name>
    <phone>0670390514</phone>
    <email>e.crea@gimema.it</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Aou Ospedali Riuniti &quot;Umberto I - G.M. Lancisi - G. Salesi&quot;- Ancona - Sod Clinica Ematologica</name>
      <address>
        <city>Ancona</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Attilio Olivieri</last_name>
      <phone>3289558821</phone>
      <email>a.olivieri@univpm.it</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Area Vasta N. 5 Ascoli Piceno - S. Benedetto Del Tronto, Presidio Ospedaliero Av5 Osp. Gen. Prov.Le &quot;C.G.Mazzoni&quot; - Uoc Ematologia</name>
      <address>
        <city>Ascoli Piceno</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Piero Galieno</last_name>
      <phone>3388149974</phone>
      <email>piero.galieni@sanita.marche.it</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Ao Di Rilievo Nazionale E Di Alta Specialità &quot;San Giuseppe Moscati&quot; - Avellino - Uoc Ematologia Con Unità Di Trapianto</name>
      <address>
        <city>Avellino</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lidia Santoro</last_name>
      <phone>3497493093</phone>
      <email>lidiasantoro63@libero.it</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Aou Consorziale Policlinico - Bari - Uo Ematologia Con Trapianto</name>
      <address>
        <city>Bari</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Pellegrino Musto</last_name>
      <phone>3683287324</phone>
      <email>pellegrino.musto@uniba.it</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Asst Papa Giovanni Xxiii - Ospedale Di Bergamo - Sc Ematologia</name>
      <address>
        <city>Bergamo</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Alessandro Rambaldi</last_name>
      <phone>3484526901</phone>
      <email>arambaldi@asst-pg23.it</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Aou Di Bologna - Policlinico S. Orsola-Malpighi - Uoc Ematologia</name>
      <address>
        <city>Bologna</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Cristina Papayannidis</last_name>
      <phone>3496484441</phone>
      <email>cristina.papayannidis@unibo.it</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Asst Degli Spedali Civili Di Brescia - Uo Ematologia</name>
      <address>
        <city>Brescia</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Erika Borlenghi</last_name>
      <phone>3402526539</phone>
      <email>erika.borlenghi@gmail.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Aso S. Croce E Carle - Cuneo - Sc Ematologia</name>
      <address>
        <city>Cuneo</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Daniele Mattei</last_name>
      <phone>3492202377</phone>
      <email>mattei.d@ospedale.cuneo.it</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Aou Careggi - Firenze - Sod Ematologia</name>
      <address>
        <city>Firenze</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Barbara Scappini</last_name>
      <email>scappinib@aou-careggi.toscana.it</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Aou Policlinico &quot;G. Martino&quot; - Messina - Uoc Ematologia</name>
      <address>
        <city>Messina</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Caterina Musolino</last_name>
      <email>cmusolino@unime.it</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Aulss 3 Serenissima, Ospedale Dell'Angelo - Mestre - Uo Ematologia</name>
      <address>
        <city>Mestre</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Renato Bassan</last_name>
      <phone>3398508691</phone>
      <email>Renato.Bassan@aulss3.veneto.it</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Asst Grande Ospedale Metropolitano Niguarda - Milano - Sc Ematologia</name>
      <address>
        <city>Milano</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Valentina Mancini</last_name>
      <phone>3477853916</phone>
      <email>valentina.mancini@ospedaleniguarda.it</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Irccs Ospedale S. Raffaele - Milano - Uo Oncoematologia</name>
      <address>
        <city>Milano</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Fabio Ciceri</last_name>
      <email>ciceri.clinicaltrials@hsr.it</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Aou Federico Ii - Napoli - Uoc Ematologia</name>
      <address>
        <city>Napoli</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Fabrizio Pane</last_name>
      <phone>3356687584</phone>
      <email>fabrizio.pane@unina.it</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Ao Di Perugia, Ospedale S. Maria Della Misericordia - Ematologia E Trapianto Midollo Osseo</name>
      <address>
        <city>Perugia</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Maria Paola Martelli</last_name>
      <phone>3355263859</phone>
      <email>mpmartelli@libero.it</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Ao Ospedali Riuniti Marche Nord - Ospedale San Salvatore - Pesaro - Uoc Ematologia E Centro Trapianti</name>
      <address>
        <city>Pesaro</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Giuseppe Visani</last_name>
      <phone>3397185885</phone>
      <email>giuseppe.visani@ospedalimarchenord.it</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Università Degli Studi Di Roma &quot;Sapienza&quot; - Dipartimento Di Medicina Traslazionale E Di Precisione - U.O.C. Ematologia</name>
      <address>
        <city>Roma</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sabina Chiaretti</last_name>
      <email>chiaretti@bce.uniroma1.it</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Aou &quot;San Giovanni Di Dio E Ruggi D'Aragona&quot; - Salerno - Uoc Ematologia E Trapianti Di Cellule Staminali Emopoietiche</name>
      <address>
        <city>Salerno</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Carmine S Selleri</last_name>
      <phone>3356166591</phone>
      <email>cselleri@unisa.it</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Ente Ecclesiastico Casa Sollievo Della Sofferenza - San Giovanni Rotondo - Ematologia</name>
      <address>
        <city>San Giovanni Rotondo</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nicola Cascavilla</last_name>
      <phone>333 6414606</phone>
      <email>n.cascavilla@operapadrepio.it</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Aou Senese - Uoc Ematologia E Trapianti</name>
      <address>
        <city>Siena</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Monica E Bocchia</last_name>
      <email>bocchia@unisi.it</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Aou Città Della Salute E Della Scienza, Ospedale S. Giovanni Battista Molinette - Torino - Sc Ematologia 2</name>
      <address>
        <city>Torino</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Stefano D'ardia</last_name>
      <phone>3484745268</phone>
      <email>sdardia@cittadellasalute.to.it</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Aou Integrata Di Verona, Policlinico G.B. Rossi - Uoc Ematologia</name>
      <address>
        <city>Verona</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Massimiliano Bonifacio</last_name>
      <phone>3495623655</phone>
      <email>massimiliano.bonifacio@univr.it</email>
    </contact>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>June 25, 2020</study_first_submitted>
  <study_first_submitted_qc>July 14, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 17, 2020</study_first_posted>
  <last_update_submitted>January 3, 2022</last_update_submitted>
  <last_update_submitted_qc>January 3, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">January 4, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</mesh_term>
    <mesh_term>Leukemia, Lymphoid</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ponatinib</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/NCT04475731
org study id: ALL2620
nct id: NCT04475731
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a phase II interventional trial to evaluate if the use of ponatinib, with or without
      chemotherapy, can induce a molecular remission in MRD-positive patients, in patients in
      hematologic and extra-hematologic relapse and in the few patients who never achieved an
      hematologic remission after whatever prior treatment.
This is a phase II interventional multicenter study for adult patients with Ph+ALL who:

        -  Are MRD+ (i.e. BCR-ABL1/ABL1 >0.01) (or loose their molecular response) after whichever
           kind of previous treatment. MRD positivity is indeed regarded as a relapse/resistance,
           since it represents the early recognition of cases who will eventually experience an
           hematologic recurrence of disease.

        -  Are in hematologic relapse after whichever kind of previous treatment.

        -  Have never achieved an hematologic remission at least after one month of treatment.

      Patients will be treated with Ponatinib at a dose of 45 mg/die per os for 28 days for 3
      cycles and - if in hematologic and extra-hematologic relapse/refractoriness, clinically fit
      and according to medical decision - with concurrent systemic chemotherapy. In case of CMR
      achievement, dosing will be reduced to 30 mg. In case of toxicity, Ponatinib will be reduced
      to 30 (or 15) mg daily.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: MRD negativity/reduction rate
time frame: After 3 months of treatment
description: Rate of patients who achieve a MRD negativity/MRD reduction following treatment with either Ponatinib alone or in combination with systemic chemotherapy
measure: Duration of CMR
time frame: at 24 months
description: Duration of the CMR status after 3 months of ponatinib treatment
measure: Hematologic remission rate
time frame: at 24 months
description: The achievement of an hematologic remission in patients treated for an hematologic and extra-hematoloigc relapse and for a refractory disease.
measure: Best molecular response
time frame: at 24 months
description: Best molecular response achieved during the follow-up
measure: Rate of AE/SAEs
time frame: at 24 months
description: Safety profile in terms of incidence of grade >3 CTC-NCI side effects and toxicities (AE/SAEs).
measure: Mutational analysis
time frame: at 24 months
description: Mutational analysis in terms of occurrence, type and number of BCR-ABL1 kinase domain mutations.
measure: Correlation between biological and MRD parameters
time frame: at 24 months
description: Correlation between the achievement and duration of CMR (or MRD reduction) with the type of fusion protein (e.g. p190 or p210) and the potential occurrence of mutations, as well as with additional genomic lesions.
measure: Disease free survival
time frame: 24 months
description: Time interval between the achievement of CHR after three months of ponatinib and hematologic relapse of the disease or death in CHR; patients still alive, in CHR.
measure: Overall survival
time frame: 24 months
description: Time interval between treatment start and death for any cause.
measure: Cumulative incidence of relapse
time frame: 24 months
description: Time interval between achievement of CHR after three months of ponatinib until the date of first hematologic relapse of the disease.
measure: Role of hematological profile on survival outcome
time frame: at 24 months
description: Identification of hematological profile on survival outcome
arm group label: Experimental arm
arm group type: Experimental
description: MRD+ Ph+ ALL adult patients will receive Ponatinib x 4 weeks x 3 courses; +/-Concomitant chemotherapy (according to hematologic status).
Patients will receive the study drug until disease relapse or progression.
intervention type: Drug
intervention name: Ponatinib
description: Ponatinib 45 mg/day x 4 weeks x 3 courses.
+/- chemotherapy:
vincristine or
L-VAMP (leucovorin, vincristine, aracytin, methotrexate, prednisone)
arm group label: Experimental arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Paola Fazi
phone: 0670390528
email: p.fazi@gimema.it
last name: Enrico Crea
phone: 0670390514
email: e.crea@gimema.it
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country: Italy
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Leukemia, Lymphoid
mesh term: Recurrence
mesh term: Ponatinib