<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/NCT04501614</url>
  </required_header>
  <id_info>
    <org_study_id>Ponatinib-1501</org_study_id>
    <secondary_id>2019-002549-39</secondary_id>
    <secondary_id>U1111-1225-0394</secondary_id>
    <nct_id>NCT04501614</nct_id>
  </id_info>
  <brief_title>A Study of Ponatinib With Chemotherapy in Children, Teenagers, and Adults With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia</brief_title>
  <official_title>A Pivotal Phase 1/2, Single-Arm, Open-label Study to Evaluate the Safety and Efficacy of Ponatinib With Chemotherapy in Pediatric Patients With Philadelphia Chromosome-Positive (Ph+) Acute Lymphoblastic Leukemia (ALL) Who Have Relapsed or Are Resistant or Intolerant to a Prior Tyrosine Kinase Inhibitor-Containing Therapy, or Who Have the T315I Mutation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Takeda</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Takeda</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is about an anticancer drug called ponatinib which is a tyrosine kinase inhibitor&#xD;
      given with chemotherapy to children, teenagers, and young adults up to 21 years of age with&#xD;
      Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia who have relapsed or are&#xD;
      resistant to other treatment.&#xD;
&#xD;
      The main aims of this study are to confirm the highest dose of ponatinib tablets and&#xD;
      minitablet capsules that can be given to participants with acceptable side effects, and to&#xD;
      evaluate if participant's leukemia achieves remission.&#xD;
&#xD;
      Participants will take ponatinib tablets with chemotherapy. For participants who cannot&#xD;
      swallow tablets or who are receiving less than a 10 mg dose, a capsule with small ponatinib&#xD;
      minitablets inside will be provided. Participants will take ponatinib for 10 weeks in&#xD;
      combination with chemotherapy (reinduction and consolidation blocks) and will be followed up&#xD;
      for at least 3 years.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The drug being tested in this study is called ponatinib. Ponatinib is being tested to treat&#xD;
      pediatric population who have Philadelphia chromosome-positive (Ph+) acute lymphoblastic&#xD;
      leukemia (ALL), Ph+ mixed phenotype acute leukemia (Ph+ MPAL), or Philadelphia&#xD;
      chromosome-like ALL who have relapsed or are resistant or intolerant to a prior tyrosine&#xD;
      kinase inhibitor (TKI)-containing therapy, or who have the T315I mutation.&#xD;
&#xD;
      The study will enroll approximately 68 participants. Participants will be assigned to a&#xD;
      treatment group either in phase 1 or phase 2. Participants unable to swallow the ponatinib&#xD;
      tablets or who are receiving less than a 10 mg dose will receive the age-appropriate&#xD;
      formulation, capsule with ponatinib minitablets inside:&#xD;
&#xD;
      • Ponatinib + Chemotherapy&#xD;
&#xD;
      All participants will be asked to take ponatinib once daily. In phase 1 ponatinib will be&#xD;
      administered in combination with a chemotherapy backbone to determine the recommended phase 2&#xD;
      dose (RP2D) of ponatinib. In both phase 1 and phase 2, treatment consists of two 35-day&#xD;
      blocks of therapy (reinduction block and consolidation block). Each block will include 29&#xD;
      days of treatment of daily ponatinib and a chemotherapy backbone regimen followed by a rest&#xD;
      period from chemotherapy for a minimum of 6 days consisting of daily ponatinib only.&#xD;
&#xD;
      This is a multi-center trial and will be conducted worldwide. The overall time to participate&#xD;
      in this study is 6.5 years. Participants will make multiple visits to the clinic, and may be&#xD;
      contacted by telephone in at least 36 months of follow-up after treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">February 24, 2021</start_date>
  <completion_date type="Anticipated">August 27, 2027</completion_date>
  <primary_completion_date type="Anticipated">February 27, 2025</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>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Phase 1: Recommended Phase 2 Dose (RP2D) of Ponatinib in Combination With Chemotherapy</measure>
    <time_frame>Up to Week 4</time_frame>
    <description>The RP2D is the maximum tolerated dose (MTD) or less.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase 2: Complete Remission (CR) Rate at the end of Reinduction Block</measure>
    <time_frame>Up to Week 4</time_frame>
    <description>CR rate is defined as percentage of participants with CR at end of reinduction block. CR is defined as no circulating blasts and &lt;5% blasts in the bone marrow (BM); normal maturation of all cellular components in the bone marrow; no extramedullary disease; absolute neutrophil count (ANC) &gt;1000 cells/microliter (μL) (or &gt;1.0 × 10^9 cells/liter [L]); Platelets &gt;100,000/μL (or &gt;100 × 10^9 platelets/L).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Phase 1: CR Rate at the end of Reinduction Block</measure>
    <time_frame>Up to Week 4</time_frame>
    <description>CR rate is defined as percentage of participants with CR at end of reinduction block. CR is defined as no circulating blasts and &lt;5% blasts in the BM; normal maturation of all cellular components in the bone marrow; no extramedullary disease; absolute neutrophil count (ANC) &gt;1000 cells/μL (or &gt;1.0 × 10^9 cells/L); Platelets &gt;100,000/μL (or &gt;100 × 10^9 platelets/L).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2: Percentage of Ph+ ALL Participants or who Achieved CR at the End of Consolidation Block</measure>
    <time_frame>Up to Week 8</time_frame>
    <description>CR is defined as no circulating blasts and &lt;5% blasts in the bone marrow; normal maturation of all cellular components in the bone marrow; no extramedullary disease; ANC &gt;1000 cells/μL (or &gt;1.0 × 10^9 cells/L); Platelets &gt;100,000 platelets/μL (or &gt;100 × 10^9 platelets/L).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2: Percentage of Ph+ ALL Participants with Negative Minimal Residual Disease (MRD) Among Those who Achieved CR</measure>
    <time_frame>Up to Weeks 4 and 8</time_frame>
    <description>MRD negative rate is the percentage of participants who achieve MRD negative status by evaluation of bone marrow aspirate at &lt;0.01% threshold.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2: Percentage of Participants who Relapsed or Progressed Following Reinduction and Consolidation</measure>
    <time_frame>Up to Weeks 4 and 8</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2: Event-free Survival (EFS)</measure>
    <time_frame>Up to approximately 36 months</time_frame>
    <description>EFS is defined as time from date of enrollment until death due to any cause; refractory to treatment (defined as failure to achieve CR by end of the consolidation block) or relapse from CR. CR is defined as no circulating blasts and &lt;5% blasts in the bone marrow; normal maturation of all cellular components in the bone marrow; no extramedullary disease; ANC &gt;1000 cells/μL (or &gt;1.0 × 10^9 cells/L); Platelets &gt;100,000 platelets/μL (or &gt;100 × 10^9 platelets/L).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2: Progression-free Survival (PFS)</measure>
    <time_frame>Up to approximately 36 months</time_frame>
    <description>PFS is defined as time from date of enrolment until death related to disease under study; disease progression (clinical deterioration associated with disease process, including evidence of increasing blasts in the bone marrow from baseline and/or evidence of new organ involvement) or relapse from CR. CR is defined as no circulating blasts and &lt;5% blasts in the bone marrow; normal maturation of all cellular components in the bone marrow; no extramedullary disease; ANC &gt;1000 cells/μL (or &gt;1.0 × 10^9 cells/L); Platelets &gt;100,000 platelets/μL (or &gt;100 × 10^9 platelets/L).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2: Overall Survival (OS)</measure>
    <time_frame>Up to approximately 36 months</time_frame>
    <description>OS is defined as time from first dose of ponatinib until death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2: Duration of Response (DOR)</measure>
    <time_frame>Up to approximately 36 months</time_frame>
    <description>DOR is defined as the interval between the first assessment at which the criteria for CR are met until the time at which relapse from CR occurs. CR is defined as no circulating blasts and &lt;5% blasts in the bone marrow; normal maturation of all cellular components in the bone marrow; no extramedullary disease; ANC &gt;1000 cells/μL (or &gt;1.0 × 10^9 cells/L); Platelets &gt;100,000 platelets/μL (or &gt;100 × 10^9 platelets /L).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2: Percentage of Participants who Underwent Hematopoietic Stem Cell Transplantation (HSCT)</measure>
    <time_frame>Up to approximately 36 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1: Cmax: Maximum Observed Plasma Concentration for Ponatinib</measure>
    <time_frame>Predose and at multiple timepoints (Up to 24 hours) postdose on Days 1 and 22</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1: tmax: Time of First Occurrence of Cmax for Ponatinib</measure>
    <time_frame>Predose and at multiple timepoints (Up to 24 hours) postdose on Days 1 and 22</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1: AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Ponatinib</measure>
    <time_frame>Predose and at multiple timepoints (Up to 24 hours) postdose on Days 1 and 22</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1 and 2: Number of Participants with Adverse Events (AEs), Serious Adverse Events (SAEs), Venous Thrombotic/Embolic Events (VTEs), and Adverse Events of Special Interest (AESIs)</measure>
    <time_frame>From the first dose of study drug up to 30 days after last dose of study drug (Up to 36 months)</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">68</enrollment>
  <condition>Pediatric Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia (Ph+ALL)</condition>
  <condition>Ph+ Mixed Phenotype Acute Leukemia (MPAL)</condition>
  <condition>Philadelphia Chromosome-Like ALL (Ph-like ALL)</condition>
  <arm_group>
    <arm_group_label>Ponatinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ponatinib tablet or age appropriate formulation (AAF) [i.e., capsules with ponatinib minitablets], based on age and weight, in combination with chemotherapy backbone, orally, once daily in both reinduction block and consolidation block (35 days each including 29 days of treatment followed by rest period from chemotherapy for a minimum of 6 days consisting of daily ponatinib only) in Phase 1 to determine RP2D. In Phase 2 participants will receive ponatinib at RP2D in combination with chemotherapy backbone.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ponatinib</intervention_name>
    <description>Ponatinib tablets.</description>
    <arm_group_label>Ponatinib</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ponatinib AAF</intervention_name>
    <description>Ponatinib age appropriate formulation i.e., capsules with ponatinib minitablets.</description>
    <arm_group_label>Ponatinib</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Chemotherapy Agents</intervention_name>
    <description>Chemotherapy agents for reinduction include vincristine, dexamethasone, polyethylene glycol (PEG)-asparaginase (Erwinia asparaginase when PEG-asparaginase is not available), daunorubicin. Agents for intrathecal (IT) chemotherapy, central nervous system (CNS)-1/2: IT methotrexate chemotherapy, or CNS-3: triple intrathecal (ITT) methotrexate, hydrocortisone, cytarabine. Chemotherapy agents for consolidation include dexamethasone, vincristine, methotrexate, PEG-asparaginase (Erwinia asparaginase when PEG-asparaginase is not available), cyclophosphamide, etoposide, CNS-1/2: IT methotrexate chemotherapy, CNS-3: ITT chemotherapy methotrexate, hydrocortisone, cytarabine. The doses for chemotherapy agents for reinduction will be given as per standard of care.</description>
    <arm_group_label>Ponatinib</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Participants must have a diagnosis of Ph+ ALL, Philadelphia chromosome-positive plus&#xD;
             mixed phenotype acute leukemia (Ph+ MPAL), or Ph-like ALL with:&#xD;
&#xD;
             a) Involvement of BM with ALL, including one of the following: i. M2 BM (5%-24%&#xD;
             lymphoblasts): by morphology with confirmatory testing consisting of at least one of&#xD;
             the following: flow cytometry lymphoblasts ≥5%, or BCR-ABL1 fluorescence in situ&#xD;
             hybridization, or ≥10-2 leukemic clone identified by immunoglobulin heavy chain-T-cell&#xD;
             receptor polymerase chain reaction, OR ii. M3 BM (≥25% lymphoblasts): by morphology,&#xD;
             OR iii. Participants with combined BM (as defined above) and extramedullary disease.&#xD;
&#xD;
             b) Evidence of Ph+ ALL, MPAL, or Ph-like ALL: i. Definite evidence of BCR-ABL1 fusion&#xD;
             (Ph) for Ph+ ALL and MPAL, OR ii. Definite evidence of Ph-like ALL with targetable&#xD;
             kinase-activating lesions involving any of the following kinase genes: ABL1, ABL2,&#xD;
             CSF1R, and PDGFRB.&#xD;
&#xD;
             Ph-like ALL diagnosis requires the identification of specified targetable&#xD;
             kinase-activating lesions preferably by ribonucleic acid (RNA) sequencing or by&#xD;
             alternative accredited method used by the site.&#xD;
&#xD;
             c) Disease status: (i) For non-US sites: participants who have relapsed (post 0 or 1&#xD;
             HSCT) or are resistant or intolerant to at least one prior therapy that contained a&#xD;
             BCR-ABL-targeted tyrosine kinase inhibitor (TKI), or for US sites: participants who&#xD;
             have relapsed (post 0 or 1 HSCT) or are resistant or intolerant to at least one prior&#xD;
             therapy that contained a second-generation BCR-ABL1-targeted TKI (i.e, dasatinib,&#xD;
             nilotinib, and bosutinib); OR (ii) Have a BCR-ABL1 T315I mutation irrespective of&#xD;
             relapse, resistance/intolerance, or transplant status and irrespective of any prior&#xD;
             TKI use.&#xD;
&#xD;
             Notes:&#xD;
&#xD;
             A participant will be defined as intolerant if they had a Grade ≥3 nonhematologic&#xD;
             toxicity or a Grade 4 hematologic toxicity considered related to the last TKI and&#xD;
             lasting for &gt;2 weeks, and led to discontinuation of therapy.&#xD;
&#xD;
          2. Weight: Participants must be weighing at least 5 kg at the time of enrollment.&#xD;
&#xD;
          3. Performance Status: Karnofsky performance status ≥50% for participants ≥16 years of&#xD;
             age or Lansky Play Scale ≥50% for participants &lt;16 years of age.&#xD;
&#xD;
          4. Have recovered to less than Grade 2 National Cancer Institute common terminology&#xD;
             criteria for adverse events (NCI CTCAE) Version 5.0, or to baseline, from any&#xD;
             nonhematologic toxicities (except alopecia) due to previous therapy.&#xD;
&#xD;
          5. Participants must meet the following criteria related to prior therapies:&#xD;
&#xD;
               -  Cytoreduction with hydroxyurea: Hydroxyurea can be initiated and continued for up&#xD;
                  to 24 hours before the start of protocol therapy.&#xD;
&#xD;
               -  Participants who relapsed while receiving cytotoxic therapy: At least 14 days&#xD;
                  must have passed since the completion of the last dose of chemotherapy before the&#xD;
                  first dose of ponatinib can be given except for the following: intrathecal (IT)&#xD;
                  chemotherapy and/or maintenance therapy such as vincristine, mercaptopurine,&#xD;
                  methotrexate, or glucocorticoids. There is no waiting period for those relapsing&#xD;
                  on maintenance-like therapy.&#xD;
&#xD;
               -  HSCT: Participants who have experienced relapse after a HSCT are eligible,&#xD;
                  provided they have no evidence of acute or chronic graft-versus-host disease&#xD;
                  (GVHD), are not receiving GVHD prophylaxis or treatment, and are at least 90 days&#xD;
                  posttransplant at the time of enrollment.&#xD;
&#xD;
               -  Hematopoietic growth factors: Before the first dose of ponatinib, at least 7 days&#xD;
                  must have passed since completion of therapy with granulocyte colony-stimulating&#xD;
                  factor or other growth factors, and at least 14 days must have passed since&#xD;
                  completion of therapy with pegfilgrastim.&#xD;
&#xD;
               -  Biologics and targeted therapies: Before the first dose of ponatinib, at least 7&#xD;
                  days must have passed since the last dose of a biologic agent. For agents that&#xD;
                  have known AEs occurring beyond 7 days after administration, this period must be&#xD;
                  extended beyond the time during which AEs are known to occur. The duration of&#xD;
                  this interval must be discussed with the sponsor's medical monitor/designee.&#xD;
&#xD;
               -  Monoclonal antibodies: After the last dose of monoclonal antibody, at least 3&#xD;
                  half-lives of the administered antibody must have passed before the first dose of&#xD;
                  ponatinib.&#xD;
&#xD;
               -  Immunotherapy: Before the first dose of ponatinib, at least 30 days must have&#xD;
                  passed after the completion of any type of immunotherapy (eg, tumor vaccines,&#xD;
                  chimeric antigen receptor T-cell [CAR-T-cell]).&#xD;
&#xD;
               -  Immunosuppressive therapy: Before the first dose of ponatinib, at least 14 days&#xD;
                  must have passed after the completion of immunosuppressive therapy (including&#xD;
                  regimens following stem cell transplant).&#xD;
&#xD;
               -  Radiotherapy: No washout period is necessary for radiation given to any&#xD;
                  extramedullary site other than central nervous system (CNS); ≥90 days must have&#xD;
                  passed if participant received prior total body irradiation or craniospinal or&#xD;
                  cranial radiotherapy.&#xD;
&#xD;
               -  Anthracyclines: Participants must have had a lifetime exposure of &lt;400 milligrams&#xD;
                  per square meter (mg/m^2) of doxorubicin equivalents of anthracyclines.&#xD;
&#xD;
          6. a) Adequate renal function defined as: Estimated glomerular filtration rate (eGFR)&#xD;
             using the Schwartz formula, OR radioisotope glomerular filtration rate (GFR)≥70&#xD;
             mL/min/1.73 m^2, OR a normal serum creatinine based on age and sex.&#xD;
&#xD;
             b) Adequate liver function defined as: Direct bilirubin ≤1.5 times the upper limit of&#xD;
             normal (ULN) for age AND ALT ≤5 times the ULN for age.&#xD;
&#xD;
          7. No clinical, radiological or laboratory evidence of pancreatitis, including:&#xD;
&#xD;
               1. Serum lipase must be &lt;2 times the ULN, AND&#xD;
&#xD;
               2. Serum amylase must be &lt;2 times the ULN.&#xD;
&#xD;
          8. Adequate cardiac function defined as shortening fraction ≥27% by echocardiogram (ECHO)&#xD;
             OR left ventricular ejection fraction of ≥50% by ECHO or multigated acquisition scan&#xD;
             (MUGA).&#xD;
&#xD;
          9. Normal QT interval with Fridericia correction method (QTcF) on screening&#xD;
             electrocardiogram (ECG), defined as QTcF of ≤450 milliseconds (ms).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. A history or current diagnosis of Burkitt leukemia/lymphoma or mature B-cell leukemia.&#xD;
&#xD;
          2. A history or current diagnosis of chronic myeloid leukemia (CML).&#xD;
&#xD;
          3. Diagnosis of ALL, MPAL, or Ph-like ALL with targetable kinase-activating lesions after&#xD;
             treatment with cytotoxic therapy for another cancer.&#xD;
&#xD;
          4. Diagnosis of another concurrent primary malignancy.&#xD;
&#xD;
          5. Clinically significant cardiovascular disease, including but not limited to:&#xD;
&#xD;
               1. Any history of myocardial infarction (MI) or unstable angina.&#xD;
&#xD;
               2. History of or presence of heart block, and/or clinically significant ventricular&#xD;
                  or atrial arrhythmias.&#xD;
&#xD;
               3. Uncontrolled hypertension, defined as persistent elevation of systolic and/or&#xD;
                  diastolic blood pressures to ≥95th percentile based on age, sex, and height&#xD;
                  percentiles despite appropriate antihypertensive management.&#xD;
&#xD;
          6. Current systemic use of drug(s) that are known to have a risk of causing prolonged&#xD;
             corrected QT interval (QTc) or torsades de pointes unless drug(s) can be changed to&#xD;
             acceptable alternatives (ie, an alternate class of agents that do not affect the&#xD;
             cardiac conduction system) or the participants can safely discontinue the drug(s).&#xD;
&#xD;
          7. Uncontrolled hypertriglyceridemia (triglycerides ≥450 milligrams per deciliter&#xD;
             (mg/dL)).&#xD;
&#xD;
          8. Current systemic use of any medications or herbal supplements that are known to be&#xD;
             strong inhibitors or strong inducers of cytochrome P450 3A (CYP3A) within 7 days&#xD;
             before the first dose of study drug.&#xD;
&#xD;
          9. Previous treatment with ponatinib.&#xD;
&#xD;
         10. Planned non-protocol chemotherapy, radiation therapy, another investigational agent,&#xD;
             or immunotherapy while participant is on study treatment.&#xD;
&#xD;
         11. Known gastrointestinal disease or gastrointestinal procedure that could interfere with&#xD;
             the oral absorption of ponatinib.&#xD;
&#xD;
         12. Participants with deoxyribonucleic acid (DNA) fragility syndromes, such as Fanconi&#xD;
             anemia and Bloom syndrome.&#xD;
&#xD;
         13. Participants with Down syndrome.&#xD;
&#xD;
         14. Participants with uncontrolled systemic infection, or known laboratory and/or clinical&#xD;
             evidence of active infection with human immunodeficiency virus (HIV), hepatitis B, or&#xD;
             hepatitis C.&#xD;
&#xD;
         15. Participants with pre-existing significant CNS pathology, including history of severe&#xD;
             brain injury, dementia, cerebellar disease, organic brain syndrome, psychosis,&#xD;
             coordination/movement disorder, or autoimmune disease with CNS involvement, are not&#xD;
             eligible.&#xD;
&#xD;
         16. Participants with a history of cerebrovascular ischemia/hemorrhage with residual&#xD;
             deficits are not eligible. (Participants with a history of cerebrovascular&#xD;
             ischemia/hemorrhage remain eligible provided all neurologic deficits and causative&#xD;
             factor(s) have resolved).&#xD;
&#xD;
         17. Uncontrolled seizure disorder. (Participants with seizure disorders that do not&#xD;
             require antiepileptic drugs or are well controlled with stable doses of antiepileptic&#xD;
             drugs are eligible).&#xD;
&#xD;
         18. History of severe coagulopathy or cardiovascular or peripheral vascular events.&#xD;
&#xD;
         19. Treatment with live attenuated vaccinations within 30 days prior to initiation of&#xD;
             study treatment regimen.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Year</minimum_age>
    <maximum_age>21 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Study Director</last_name>
    <role>Study Director</role>
    <affiliation>Takeda</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Takeda Contact</last_name>
    <phone>+1-877-825-3327</phone>
    <email>medinfoUS@takeda.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Phoenix Childrens Hospital</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85016</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>602-933-0920</phone>
      <email>mhenry@phoenixchildrens.com</email>
    </contact>
    <investigator>
      <last_name>Michael Henry</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Arkansas Children's Hospital</name>
      <address>
        <city>Little Rock</city>
        <state>Arkansas</state>
        <zip>72202</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>501-364-3058</phone>
      <email>kjbielamowicz2@uams.edu</email>
    </contact>
    <investigator>
      <last_name>Kevin Bielamowicz</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Children's Hospital Los Angeles</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90027</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>323-361-4829</phone>
      <email>andoan@chla.usc.edu</email>
    </contact>
    <investigator>
      <last_name>Andrew Doan</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Rady Childrens Hospital San Diego - PIN</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92123</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>858-966-5811</phone>
      <email>vwong@rchsd.org</email>
    </contact>
    <investigator>
      <last_name>Victor Wong</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>UCSF Medical Comprehensive Cancer</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>415-541-0853</phone>
      <email>mignon.loh@ucsf.edu</email>
    </contact>
    <investigator>
      <last_name>Ben Braun</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Alfred I Dupont Hospital For Children</name>
      <address>
        <city>Wilmington</city>
        <state>Delaware</state>
        <zip>19803</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>302-651-5584</phone>
      <email>emi.caywood@nemours.org</email>
    </contact>
    <investigator>
      <last_name>Emi Caywood</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Ann and Robert H Lurie Childrens Hospital of Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>312-227-4090</phone>
      <email>jrossoff@luriechildrens.org</email>
    </contact>
    <investigator>
      <last_name>Jenna Rossoff</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Riley Hospital For Children</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>317-944-8784</phone>
      <email>batras@iu.edu</email>
    </contact>
    <investigator>
      <last_name>Sandeep Batra</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Dana Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>617-632-2313</phone>
      <email>andrew_place@dfci.harvard.edu</email>
    </contact>
    <investigator>
      <last_name>Andrew Place</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Children's Mercy Hospital and Clinica</name>
      <address>
        <city>Kansas City</city>
        <state>Missouri</state>
        <zip>64108</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>614-722-3562</phone>
      <email>kginn@cmh.edu</email>
    </contact>
    <investigator>
      <last_name>Kevin Ginn</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Cincinnati Children's Hospital Medical Center - PIN</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45229</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>513-803-1678</phone>
      <email>maureen.obrien@cchmc.org</email>
    </contact>
    <investigator>
      <last_name>Maureen O'Brien</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Nationwide Children's Hospital</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43205</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>816-302-6808</phone>
      <email>mark.ranalli@nationsidechildrens.org</email>
    </contact>
    <investigator>
      <last_name>Mark Ranalli</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Philadelphia</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>215-906-7885</phone>
      <email>BAILEYC@chop.edu</email>
    </contact>
    <investigator>
      <last_name>Charles L. Bailey</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>St Jude Children's Research Hospital</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38105</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>901-595-1716</phone>
      <email>seth.karol@stjude.org</email>
    </contact>
    <investigator>
      <last_name>Seth Karol</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Childrens Medical Center Research Institute at UT Southwestern</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75235</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>214-456-7000</phone>
      <email>tamra.slone@utsouthwestern.edu</email>
    </contact>
    <investigator>
      <last_name>Tamra Slone</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Austral</name>
      <address>
        <city>Pilar</city>
        <state>Buenos Aires</state>
        <zip>B1629AHJ</zip>
        <country>Argentina</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>+54 (0) 11-4469-9300</phone>
      <email>davidveronhonc@gmail.com</email>
    </contact>
    <investigator>
      <last_name>David Veron</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Italiano de Buenos Aires</name>
      <address>
        <city>Buenos Aires</city>
        <zip>C1199ABB</zip>
        <country>Argentina</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>+54 (0) 11-4959-0348</phone>
      <email>monica.makiya@hiba.org.ar</email>
    </contact>
    <investigator>
      <last_name>Monica Leonor Makiya</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Queensland Childrens Hospital</name>
      <address>
        <city>South Brisbane</city>
        <state>Queensland</state>
        <zip>4101</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>+61(0)7-3068-1119</phone>
      <email>chris.fraser@health.qld.gov.au</email>
    </contact>
    <investigator>
      <last_name>Christopher Fraser</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Royal Children's Hospital Melbourne - PIN</name>
      <address>
        <city>Parkville</city>
        <state>Victoria</state>
        <zip>3052</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>61393459184</phone>
      <email>jordan.hansford@rch.org.au</email>
    </contact>
    <investigator>
      <last_name>David Hughes</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Perth Childrens Hospital</name>
      <address>
        <city>Nedlands</city>
        <state>Western Australia</state>
        <zip>6009</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>61893408222</phone>
      <email>marianne.phillips@health.wa.gov.au</email>
    </contact>
    <investigator>
      <last_name>Marianne Phillips</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Rua Ramiro Barcelos, 2350</name>
      <address>
        <city>Curitiba</city>
        <state>Parana</state>
        <zip>81520-060</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>+55 41 3361-5195</phone>
      <email>mpianovski@erastinho.com.br</email>
    </contact>
    <investigator>
      <last_name>Mara Pianovsky</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Irmandade Da Santa Casa de Misericordia de Porto Alegre</name>
      <address>
        <city>Porto Alegre</city>
        <state>Rio Grande Du Sul</state>
        <zip>90020-090</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>+55 51 32148143</phone>
      <email>pesquisaclinica@santacasa.org.br</email>
    </contact>
    <investigator>
      <last_name>Camila Voos Soares</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital de Clinicas de Porto Alegre (HCPA) - PPDS</name>
      <address>
        <city>Porto Alegre</city>
        <state>Rio Grande Du Sul</state>
        <zip>90035-903</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>5133598317</phone>
      <email>ldaudt@hcpa.edu.br</email>
    </contact>
    <investigator>
      <last_name>Liane Esteves Daudt</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Clinica SUPRA</name>
      <address>
        <city>Chapeco</city>
        <state>Santa Catarina</state>
        <zip>89801-355</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Fundacao Pio XII Hospital de Cancer de Barretos</name>
      <address>
        <city>Barretos</city>
        <state>Sao Paulo</state>
        <zip>14784-400</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>551733216637</phone>
      <email>brunamancano@gmail.com</email>
    </contact>
    <investigator>
      <last_name>Bruna Minniti Mancano</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Das Clinicas da Faculdade de Medicina de Ribeirao Preto - USP</name>
      <address>
        <city>Ribeirao Preto</city>
        <zip>14051-140</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>55 16 39636482</phone>
      <email>mbergamo@hcrp.usp.br</email>
    </contact>
    <investigator>
      <last_name>Maristella dos Reis</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Graacc Grupo de Apoio Ao Adolescente E A Crianca Com Cancer</name>
      <address>
        <city>Sao Paulo</city>
        <zip>04039-001</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>55 11 50808488</phone>
      <email>avlsousa@hotmail.com</email>
    </contact>
    <investigator>
      <last_name>Ana Virginia Lopes de Sousa</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Santa Marcelina</name>
      <address>
        <city>Sao Paulo</city>
        <zip>08270-070</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>55 11 25222472</phone>
      <email>inctr@inctrbrasil.org</email>
    </contact>
    <investigator>
      <last_name>Sidnei Epelman</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>West China Second University Hospital, Sichuan Univesity</name>
      <address>
        <city>Chengdu</city>
        <zip>610041</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>8613111854621</phone>
      <email>gaoju651220@126.com</email>
    </contact>
    <investigator>
      <last_name>Ju Gao</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Chongqing Medical University</name>
      <address>
        <city>Chongqing</city>
        <zip>400014</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>+86 13983762652</phone>
      <email>1808106657@qq.com</email>
    </contact>
    <investigator>
      <last_name>Jie Yu</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>The Affiliated Hospital of Guizhou Medical University</name>
      <address>
        <city>Guiyang</city>
        <zip>550004</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>8615180802411</phone>
      <email>jinjiao999@163.com</email>
    </contact>
    <investigator>
      <last_name>Jiao Jin</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>The Second Hospital of Anhui Medical University</name>
      <address>
        <city>Hefei</city>
        <zip>230601</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>8655163869420</phone>
      <email>zwnltt@126.com</email>
    </contact>
    <investigator>
      <last_name>Ningling Wang</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Qilu Hospital of Shandong University</name>
      <address>
        <city>Jinan</city>
        <zip>250012</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>86053182169229</phone>
      <email>shellysdcn@hotmail.com</email>
    </contact>
    <investigator>
      <last_name>Xiu-li Ju</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>The Affiliated Hospital of Qingdao University</name>
      <address>
        <city>Qingdao</city>
        <zip>260003</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>+86 18661807165</phone>
      <email>sunlr@vip.sina.com</email>
    </contact>
    <investigator>
      <last_name>Lirong Sun</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Shanghai</name>
      <address>
        <city>Shanghai</city>
        <zip>200040</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>8618917128021</phone>
      <email>jhui0111@126.com</email>
    </contact>
    <investigator>
      <last_name>Hui Jiang</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Shanghai Childrens Medical Center</name>
      <address>
        <city>Shanghai</city>
        <zip>200127</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>8618930830638</phone>
      <email>shenshuhong@scmc.com.cn</email>
    </contact>
    <investigator>
      <last_name>Shuhong Shen</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Soochow University</name>
      <address>
        <city>Suzhou</city>
        <zip>215025</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>+86 137 7187 0462</phone>
      <email>hsy139@126.com</email>
    </contact>
    <investigator>
      <last_name>Shaoyan Hu</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences</name>
      <address>
        <city>Tianjin</city>
        <zip>300020</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <email>xfzhu1981@126.com</email>
    </contact>
    <investigator>
      <last_name>Xiaofan Zhu</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Union Hospital Tongji Medical College Huazhong University of Science and Technology</name>
      <address>
        <city>Wuhan</city>
        <zip>430022</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <email>jinrunm@qq.com</email>
    </contact>
    <investigator>
      <last_name>Runming Jin</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Tongji Hospital Tongji Medical College Huazhong University of Science and Technology</name>
      <address>
        <city>Wuhan</city>
        <zip>430030</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>+86 18971353983</phone>
      <email>qunhu2013@163.com</email>
    </contact>
    <investigator>
      <last_name>Qun Hu</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Fakultni nemocnice Brno</name>
      <address>
        <city>Brno</city>
        <zip>61300</zip>
        <country>Czechia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>420532234831</phone>
      <email>domansky.jiri@fnbrno.cz</email>
    </contact>
    <investigator>
      <last_name>Jiri Domansky</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Fakultni nemocnice v Motole</name>
      <address>
        <city>Praha</city>
        <zip>15006</zip>
        <country>Czechia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>420224436400</phone>
      <email>jan.stary@lfmotol.cuni.cz</email>
    </contact>
    <investigator>
      <last_name>Jan Star</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hopital Sud</name>
      <address>
        <city>Rennes</city>
        <state>Ille-et-Vilaine</state>
        <zip>35200</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>33299267162</phone>
      <email>virginie.gandemer@chu-rennes.fr</email>
    </contact>
    <investigator>
      <last_name>Virginie Gandemer</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Assistance Publique Hopitaux de Marseille</name>
      <address>
        <city>Marseille</city>
        <zip>13385</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>+33 4 91 38 68 19</phone>
      <email>paul.saultier@ap-hm.fr</email>
    </contact>
    <investigator>
      <last_name>Paul Saultier</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hopital Robert Debre</name>
      <address>
        <city>Paris</city>
        <zip>75019</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>33140035388</phone>
      <email>marion.strullu@aphp.fr</email>
    </contact>
    <investigator>
      <last_name>Marion Strullo</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hopital Des Enfants</name>
      <address>
        <city>Toulouse</city>
        <zip>31059</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>33534558611</phone>
      <email>pasquet.m@chu-toulouse.fr</email>
    </contact>
    <investigator>
      <last_name>Marlene Pasquet</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>IRCCS Ospedale Pediatrico Bambino Gesu - INCIPIT - PIN</name>
      <address>
        <city>Roma</city>
        <state>Lazio</state>
        <zip>165</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>+390668592129</phone>
      <email>franco.locatelli@opbg.net</email>
    </contact>
    <investigator>
      <last_name>Franco Locatelli</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Istituto G Gaslini Ospedale Pediatrico IRCCS - INCIPIT - PIN</name>
      <address>
        <city>Genova</city>
        <state>Liguria</state>
        <zip>16147</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
    </contact>
    <investigator>
      <last_name>Concetta Micalizzi</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Fndazione MBBM (MONZA E BRIANZA PER IL BAMBINO E LA SUA MAMMA) - c/o Centro Maria Letizia Verga</name>
      <address>
        <city>Monza</city>
        <state>Lombardia</state>
        <zip>20900</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>+390392334915</phone>
      <email>verix.leo@gmail.com</email>
    </contact>
    <investigator>
      <last_name>Veronica Leoni</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Ospedale Infantile Regina Margherita - INCIPIT - PIN</name>
      <address>
        <city>Torino</city>
        <state>Piemonte</state>
        <zip>10126</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>+39011 3131865</phone>
      <email>nbertore@gmail.com</email>
    </contact>
    <investigator>
      <last_name>Nicoletta Bertorello</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Seoul National University Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>3080</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>+82 2 2072 3304</phone>
      <email>kanghj@snu.ac.kr</email>
    </contact>
    <investigator>
      <last_name>Hyoung Jin Kang</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Severance Hospital Yonsei University Health System</name>
      <address>
        <city>Seoul</city>
        <zip>3722</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>+82222282060</phone>
      <email>cj@yuhs.ac</email>
    </contact>
    <investigator>
      <last_name>Chuhl Joo Lyu</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Asan Medical Center - PPDS</name>
      <address>
        <city>Seoul</city>
        <zip>5505</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>+82-2-3010-7196</phone>
      <email>hojim@amc.seoul.kr</email>
    </contact>
    <investigator>
      <last_name>Ho-Joon Im</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>The Catholic University of Korea, Seoul St. Mary's Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>6591</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>+82 2 2258 6188</phone>
      <email>cngped@catholic.ac.kr</email>
    </contact>
    <investigator>
      <last_name>Nack Gyun Chung</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Dr. Jose Eleuterio Gonzalez</name>
      <address>
        <city>Monterrey</city>
        <state>Nuevo Leon</state>
        <zip>64460</zip>
        <country>Mexico</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>+528183486136</phone>
      <email>investigacionhematohu@gmail.com</email>
    </contact>
    <investigator>
      <last_name>Dinorah Catalina Barrera Molina</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Instituto Nacional de Pediatria</name>
      <address>
        <city>Ciudad De Mexico</city>
        <zip>4530</zip>
        <country>Mexico</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>+525510840912</phone>
      <email>alberto.olaya@yahoo.com.mx</email>
    </contact>
    <investigator>
      <last_name>Alberto Olaya Vargas</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Nuevo Hospital Civil de Guadalajara Dr. Juan I. Menchaca</name>
      <address>
        <city>Guadalajara</city>
        <zip>44340</zip>
        <country>Mexico</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>+3339424400</phone>
      <email>hugoromo48@gmail.com</email>
    </contact>
    <investigator>
      <last_name>Hugo Antonio Romo Rubio</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Princess Maxima Center for Pediatric Oncology - PIN</name>
      <address>
        <city>Utrecht</city>
        <zip>3584 CS</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>+31107036691</phone>
      <email>i.m.vandersluis@prinsesmaximacentrum.nl</email>
    </contact>
    <investigator>
      <last_name>Inge van der Sluis</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Uniwersytecki Szpital Dzieciecy</name>
      <address>
        <city>Krakow</city>
        <zip>30-663</zip>
        <country>Poland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>+48 12 333 92 20</phone>
      <email>skoczenkr@interia.pl</email>
    </contact>
    <investigator>
      <last_name>Szymon Skoczen</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>SPZOZ Centralny Szpital Kliniczny UM w Lodzi</name>
      <address>
        <city>Lodz</city>
        <zip>91-738</zip>
        <country>Poland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>+48 4261 77750</phone>
      <email>wojciech.mlynarski@umed.lodz.pl</email>
    </contact>
    <investigator>
      <last_name>Wojciech Mlynarski</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>SPSK Nr 1 im. Prof.Stanislawa Szyszko Slaskiego Uniwersytetu Medycznego</name>
      <address>
        <city>Zabrze</city>
        <zip>41-800</zip>
        <country>Poland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>48323704372</phone>
      <email>szczep57@poczta.onet.pl</email>
    </contact>
    <investigator>
      <last_name>Tomasz Szczepanski</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Instituto Portugues de Oncologia de Lisboa Francisco Gentil, E.P.E.</name>
      <address>
        <city>Lisbon</city>
        <state>Lisboa</state>
        <zip>1099-023</zip>
        <country>Portugal</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>351217229891</phone>
      <email>jduarte@ipolisboa.min-saude.pt</email>
    </contact>
    <investigator>
      <last_name>Joaquin Duarte</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Instituto Portugues de Oncologia Do Porto Francisco Gentil Epe - PPDS</name>
      <address>
        <city>Porto</city>
        <zip>4200-072</zip>
        <country>Portugal</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <email>ana.ferreira@ipoporto.min-saude.pt</email>
    </contact>
    <investigator>
      <last_name>Ana Maia Ferreira</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Vall d'Hebron - PPDS</name>
      <address>
        <city>Barcelona</city>
        <zip>8035</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>+34934893093</phone>
      <email>alba.rubio@salud.madrid.org</email>
    </contact>
    <investigator>
      <last_name>Pablo Velasco Puyo</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Infantil Universitario Nino Jesus - PIN</name>
      <address>
        <city>Madrid</city>
        <zip>28009</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>+34915035900 ext 662</phone>
      <email>alba.rubio@salud.madrid.org</email>
    </contact>
    <investigator>
      <last_name>Alba Rubio San Simon</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen del Rocio - PPDS</name>
      <address>
        <city>Sevilla</city>
        <zip>41013</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <email>jose.gonzalez.sspa@juntadeandalucia.es</email>
    </contact>
    <investigator>
      <last_name>Jose Gonzalez Campos</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Royal Marsden Hospital - Surrey</name>
      <address>
        <city>Surrey Quays</city>
        <state>Sutton</state>
        <zip>SM2 5PT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>+442086613496</phone>
      <email>donna.lancaster@rmh.nhs.uk</email>
    </contact>
    <investigator>
      <last_name>Donna Lancaster</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Birmingham Childrens Hospital</name>
      <address>
        <city>Birmingham</city>
        <zip>B4 6NH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>+441213338712</phone>
      <email>alice.norton1@nhs.net</email>
    </contact>
    <investigator>
      <last_name>Alice Norton</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Cambridge University Hospitals NHS Foundation Trust</name>
      <address>
        <city>Cambridge</city>
        <zip>CB2 0QQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>+441865741166</phone>
      <email>emmy.dickens@nhs.net</email>
    </contact>
    <investigator>
      <last_name>Emmy Dickens</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Royal Hospital for Children (Glasgow) - PPDS - PIN</name>
      <address>
        <city>Glasgow</city>
        <zip>G3 8SJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>+441412010675</phone>
      <email>brenda.gibson@ggc.scot.nhs.uk</email>
    </contact>
    <investigator>
      <last_name>Brenda Gibson</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Argentina</country>
    <country>Australia</country>
    <country>Brazil</country>
    <country>China</country>
    <country>Czechia</country>
    <country>France</country>
    <country>Italy</country>
    <country>Korea, Republic of</country>
    <country>Mexico</country>
    <country>Netherlands</country>
    <country>Poland</country>
    <country>Portugal</country>
    <country>Spain</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Canada</country>
    <country>Germany</country>
  </removed_countries>
  <link>
    <url>https://clinicaltrials.takeda.com/study-detail/5f929169296beb001e63bf5d</url>
    <description>Related Info</description>
  </link>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>August 4, 2020</study_first_submitted>
  <study_first_submitted_qc>August 4, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 6, 2020</study_first_posted>
  <last_update_submitted>September 14, 2023</last_update_submitted>
  <last_update_submitted_qc>September 14, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 15, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Drug Therapy</keyword>
  <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>Philadelphia Chromosome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ponatinib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_access_criteria>IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.</ipd_access_criteria>
    <ipd_url>https://vivli.org/ourmember/takeda/</ipd_url>
  </patient_data>
  <!-- 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/NCT04501614
org study id: Ponatinib-1501
secondary id: 2019-002549-39
secondary id: U1111-1225-0394
nct id: NCT04501614
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This study is about an anticancer drug called ponatinib which is a tyrosine kinase inhibitor
      given with chemotherapy to children, teenagers, and young adults up to 21 years of age with
      Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia who have relapsed or are
      resistant to other treatment.

      The main aims of this study are to confirm the highest dose of ponatinib tablets and
      minitablet capsules that can be given to participants with acceptable side effects, and to
      evaluate if participant's leukemia achieves remission.

      Participants will take ponatinib tablets with chemotherapy. For participants who cannot
      swallow tablets or who are receiving less than a 10 mg dose, a capsule with small ponatinib
      minitablets inside will be provided. Participants will take ponatinib for 10 weeks in
      combination with chemotherapy (reinduction and consolidation blocks) and will be followed up
      for at least 3 years.
The drug being tested in this study is called ponatinib. Ponatinib is being tested to treat
      pediatric population who have Philadelphia chromosome-positive (Ph+) acute lymphoblastic
      leukemia (ALL), Ph+ mixed phenotype acute leukemia (Ph+ MPAL), or Philadelphia
      chromosome-like ALL who have relapsed or are resistant or intolerant to a prior tyrosine
      kinase inhibitor (TKI)-containing therapy, or who have the T315I mutation.

      The study will enroll approximately 68 participants. Participants will be assigned to a
      treatment group either in phase 1 or phase 2. Participants unable to swallow the ponatinib
      tablets or who are receiving less than a 10 mg dose will receive the age-appropriate
      formulation, capsule with ponatinib minitablets inside:

      • Ponatinib + Chemotherapy

      All participants will be asked to take ponatinib once daily. In phase 1 ponatinib will be
      administered in combination with a chemotherapy backbone to determine the recommended phase 2
      dose (RP2D) of ponatinib. In both phase 1 and phase 2, treatment consists of two 35-day
      blocks of therapy (reinduction block and consolidation block). Each block will include 29
      days of treatment of daily ponatinib and a chemotherapy backbone regimen followed by a rest
      period from chemotherapy for a minimum of 6 days consisting of daily ponatinib only.

      This is a multi-center trial and will be conducted worldwide. The overall time to participate
      in this study is 6.5 years. Participants will make multiple visits to the clinic, and may be
      contacted by telephone in at least 36 months of follow-up after treatment.
allocation: N/A
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Phase 1: Recommended Phase 2 Dose (RP2D) of Ponatinib in Combination With Chemotherapy
time frame: Up to Week 4
description: The RP2D is the maximum tolerated dose (MTD) or less.
measure: Phase 2: Complete Remission (CR) Rate at the end of Reinduction Block
time frame: Up to Week 4
description: CR rate is defined as percentage of participants with CR at end of reinduction block. CR is defined as no circulating blasts and <5% blasts in the bone marrow (BM); normal maturation of all cellular components in the bone marrow; no extramedullary disease; absolute neutrophil count (ANC) >1000 cells/microliter (μL) (or >1.0 × 10^9 cells/liter [L]); Platelets >100,000/μL (or >100 × 10^9 platelets/L).
measure: Phase 1: CR Rate at the end of Reinduction Block
time frame: Up to Week 4
description: CR rate is defined as percentage of participants with CR at end of reinduction block. CR is defined as no circulating blasts and <5% blasts in the BM; normal maturation of all cellular components in the bone marrow; no extramedullary disease; absolute neutrophil count (ANC) >1000 cells/μL (or >1.0 × 10^9 cells/L); Platelets >100,000/μL (or >100 × 10^9 platelets/L).
measure: Phase 2: Percentage of Ph+ ALL Participants or who Achieved CR at the End of Consolidation Block
time frame: Up to Week 8
description: CR is defined as no circulating blasts and <5% blasts in the bone marrow; normal maturation of all cellular components in the bone marrow; no extramedullary disease; ANC >1000 cells/μL (or >1.0 × 10^9 cells/L); Platelets >100,000 platelets/μL (or >100 × 10^9 platelets/L).
measure: Phase 2: Percentage of Ph+ ALL Participants with Negative Minimal Residual Disease (MRD) Among Those who Achieved CR
time frame: Up to Weeks 4 and 8
description: MRD negative rate is the percentage of participants who achieve MRD negative status by evaluation of bone marrow aspirate at <0.01% threshold.
measure: Phase 2: Percentage of Participants who Relapsed or Progressed Following Reinduction and Consolidation
time frame: Up to Weeks 4 and 8
measure: Phase 2: Event-free Survival (EFS)
time frame: Up to approximately 36 months
description: EFS is defined as time from date of enrollment until death due to any cause; refractory to treatment (defined as failure to achieve CR by end of the consolidation block) or relapse from CR. CR is defined as no circulating blasts and <5% blasts in the bone marrow; normal maturation of all cellular components in the bone marrow; no extramedullary disease; ANC >1000 cells/μL (or >1.0 × 10^9 cells/L); Platelets >100,000 platelets/μL (or >100 × 10^9 platelets/L).
measure: Phase 2: Progression-free Survival (PFS)
time frame: Up to approximately 36 months
description: PFS is defined as time from date of enrolment until death related to disease under study; disease progression (clinical deterioration associated with disease process, including evidence of increasing blasts in the bone marrow from baseline and/or evidence of new organ involvement) or relapse from CR. CR is defined as no circulating blasts and <5% blasts in the bone marrow; normal maturation of all cellular components in the bone marrow; no extramedullary disease; ANC >1000 cells/μL (or >1.0 × 10^9 cells/L); Platelets >100,000 platelets/μL (or >100 × 10^9 platelets/L).
measure: Phase 2: Overall Survival (OS)
time frame: Up to approximately 36 months
description: OS is defined as time from first dose of ponatinib until death due to any cause.
measure: Phase 2: Duration of Response (DOR)
time frame: Up to approximately 36 months
description: DOR is defined as the interval between the first assessment at which the criteria for CR are met until the time at which relapse from CR occurs. CR is defined as no circulating blasts and <5% blasts in the bone marrow; normal maturation of all cellular components in the bone marrow; no extramedullary disease; ANC >1000 cells/μL (or >1.0 × 10^9 cells/L); Platelets >100,000 platelets/μL (or >100 × 10^9 platelets /L).
measure: Phase 2: Percentage of Participants who Underwent Hematopoietic Stem Cell Transplantation (HSCT)
time frame: Up to approximately 36 months
measure: Phase 1: Cmax: Maximum Observed Plasma Concentration for Ponatinib
time frame: Predose and at multiple timepoints (Up to 24 hours) postdose on Days 1 and 22
measure: Phase 1: tmax: Time of First Occurrence of Cmax for Ponatinib
time frame: Predose and at multiple timepoints (Up to 24 hours) postdose on Days 1 and 22
measure: Phase 1: AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Ponatinib
time frame: Predose and at multiple timepoints (Up to 24 hours) postdose on Days 1 and 22
measure: Phase 1 and 2: Number of Participants with Adverse Events (AEs), Serious Adverse Events (SAEs), Venous Thrombotic/Embolic Events (VTEs), and Adverse Events of Special Interest (AESIs)
time frame: From the first dose of study drug up to 30 days after last dose of study drug (Up to 36 months)
arm group label: Ponatinib
arm group type: Experimental
description: Ponatinib tablet or age appropriate formulation (AAF) [i.e., capsules with ponatinib minitablets], based on age and weight, in combination with chemotherapy backbone, orally, once daily in both reinduction block and consolidation block (35 days each including 29 days of treatment followed by rest period from chemotherapy for a minimum of 6 days consisting of daily ponatinib only) in Phase 1 to determine RP2D. In Phase 2 participants will receive ponatinib at RP2D in combination with chemotherapy backbone.
intervention type: Drug
intervention name: Ponatinib
description: Ponatinib tablets.
arm group label: Ponatinib
intervention type: Drug
intervention name: Ponatinib AAF
description: Ponatinib age appropriate formulation i.e., capsules with ponatinib minitablets.
arm group label: Ponatinib
intervention type: Drug
intervention name: Chemotherapy Agents
description: Chemotherapy agents for reinduction include vincristine, dexamethasone, polyethylene glycol (PEG)-asparaginase (Erwinia asparaginase when PEG-asparaginase is not available), daunorubicin. Agents for intrathecal (IT) chemotherapy, central nervous system (CNS)-1/2: IT methotrexate chemotherapy, or CNS-3: triple intrathecal (ITT) methotrexate, hydrocortisone, cytarabine. Chemotherapy agents for consolidation include dexamethasone, vincristine, methotrexate, PEG-asparaginase (Erwinia asparaginase when PEG-asparaginase is not available), cyclophosphamide, etoposide, CNS-1/2: IT methotrexate chemotherapy, CNS-3: ITT chemotherapy methotrexate, hydrocortisone, cytarabine. The doses for chemotherapy agents for reinduction will be given as per standard of care.
arm group label: Ponatinib
criteria: 
gender: All
minimum age: 1 Year
maximum age: 21 Years
healthy volunteers: No
last name: Study Director
role: Study Director
affiliation: Takeda
last name: Takeda Contact
phone: +1-877-825-3327
email: medinfoUS@takeda.com
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country: Argentina
country: Australia
country: Brazil
country: China
country: Czechia
country: France
country: Italy
country: Korea, Republic of
country: Mexico
country: Netherlands
country: Poland
country: Portugal
country: Spain
country: United Kingdom
country: United States
country: Canada
country: Germany
url: https://clinicaltrials.takeda.com/study-detail/5f929169296beb001e63bf5d
description: Related Info
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Leukemia, Lymphoid
mesh term: Philadelphia Chromosome
mesh term: Ponatinib
sharing ipd: Yes
ipd description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd access criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
ipd url: https://vivli.org/ourmember/takeda/