<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/NCT03263572</url>
  </required_header>
  <id_info>
    <org_study_id>2016-0792</org_study_id>
    <secondary_id>NCI-2018-01078</secondary_id>
    <secondary_id>2016-0792</secondary_id>
    <nct_id>NCT03263572</nct_id>
  </id_info>
  <brief_title>Blinatumomab, Methotrexate, Cytarabine, and Ponatinib in Treating Patients With Philadelphia Chromosome-Positive, or BCR-ABL Positive, or Relapsed/Refractory, Acute Lymphoblastic Leukemia</brief_title>
  <official_title>Phase II Study of the Combination of Blinatumomab and Ponatinib in Patients With Philadelphia Chromosome (Ph)-Positive and/or BCR-ABL Positive Acute Lymphoblastic Leukemia (ALL)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>M.D. Anderson Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Amgen</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Takeda</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>M.D. Anderson Cancer Center</source>
  <oversight_info>
    <has_dmc>No</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 phase II trial studies how well blinatumomab, methotrexate, cytarabine, and ponatinib&#xD;
      work in treating patients with Philadelphia chromosome (Ph)-positive, or BCR-ABL positive, or&#xD;
      acute lymphoblastic leukemia that has come back or does not respond to treatment.&#xD;
      Immunotherapy with monoclonal antibodies, such as blinatumomab, may induce changes in body's&#xD;
      immune system and may interfere with the ability of tumor cells to grow and spread. Drugs&#xD;
      used in chemotherapy, such as methotrexate and cytarabine, work in different ways to stop the&#xD;
      growth of cancer cells, either by killing the cells, by stopping them from dividing, or by&#xD;
      stopping them from spreading. Ponatinib may stop the growth of cancer cells by blocking some&#xD;
      of the enzymes needed for cell growth. Giving blinatumomab, methotrexate, cytarabine, and&#xD;
      ponatinib may work better in treating patients with acute lymphoblastic leukemia.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To evaluate the complete molecular response rate in cohort 1 (newly diagnosed Philadelphia&#xD;
      chromosome [Ph-positive] and/or BCR-ABL-positive acute lymphoblastic leukemia [ALL]) and the&#xD;
      overall response (complete remission [CR]+CR with incomplete blood count recovery [CRi]) rate&#xD;
      in cohort 2 (relapsed/refractory disease).&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To evaluate other clinical efficacy endpoints (complete cytogenetic response, complete&#xD;
      molecular response [CMR], event-free survival [EFS] and overall survival [OS]) and safety of&#xD;
      the regimen.&#xD;
&#xD;
      EXPLORATORY OBJECTIVES:&#xD;
&#xD;
      I. To characterize the role of ABL1 kinase domain mutations on treatment failure and relapse&#xD;
      in patients with Ph+ ALL treated with blinatumomab plus ponatinib.&#xD;
&#xD;
      II. To determine the impact of recurrent genomic alterations and ribonucleic acid (RNA)&#xD;
      expression at diagnosis on relapse-free survival (RFS) in patients with Ph+ ALL treated with&#xD;
      blinatumomab plus ponatinib.&#xD;
&#xD;
      III. To investigate the impact of next-generation sequencing-based minimal residual disease&#xD;
      assessment on relapse-free survival in patients with Ph+ ALL.&#xD;
&#xD;
      IV. To determine the effect on immune cell subsets in patients with Ph+ ALL treated with&#xD;
      blinatumomab plus ponatinib.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients receive blinatumomab intravenously (IV) nonstop on days 1-28 of cycles 1-5, and&#xD;
      methotrexate and cytarabine intrathecally (by spinal tap) on days 1, 15, and 29 of cycles&#xD;
      1-4. Patients also receive ponatinib orally (PO) daily. Cycles repeat every 6 weeks in the&#xD;
      absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up at 30 days and every 6 months&#xD;
      thereafter.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 29, 2017</start_date>
  <completion_date type="Anticipated">November 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">November 30, 2024</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Complete molecular response (CMR) rate in newly diagnosed Ph-positive and/or BCR-ABL-positive acute lymphoblastic leukemia (ALL)</measure>
    <time_frame>At 18 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Overall response rate (ORR) in relapsed/refractory ALL</measure>
    <time_frame>At 12 weeks</time_frame>
    <description>This is defined as the percentage of patients achieving complete remission (CR) or CR with incomplete blood count recovery (CRi).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Relapse-free survival</measure>
    <time_frame>From documented complete response until relapse or death, assessed up to 6 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Event-free survival</measure>
    <time_frame>From first day of treatment until any failure (resistant disease, relapse, or death), assessed up to 6 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Overall survival</measure>
    <time_frame>First day of treatment to time of death from any cause, assessed up to 6 years</time_frame>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">90</enrollment>
  <condition>Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive</condition>
  <condition>Acute Lymphoblastic Leukemia</condition>
  <condition>BCR-ABL1 Fusion Protein Expression</condition>
  <condition>Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive</condition>
  <condition>Philadelphia Chromosome Positive</condition>
  <condition>Recurrent Acute Lymphoblastic Leukemia</condition>
  <condition>Refractory Acute Lymphoblastic Leukemia</condition>
  <condition>t(9;22)</condition>
  <arm_group>
    <arm_group_label>Treatment (blinatumomab, chemotherapy, ponatinib)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive blinatumomab IV nonstop on days 1-28 of cycles 1-5, and methotrexate and cytarabine intrathecally (by spinal tap) on days 1, 15, and 29 of cycles 1-4. Patients also receive ponatinib PO daily. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Blinatumomab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (blinatumomab, chemotherapy, ponatinib)</arm_group_label>
    <other_name>Anti-CD19 x Anti-CD3 Bispecific Monoclonal Antibody</other_name>
    <other_name>Anti-CD19/Anti-CD3 Recombinant Bispecific Monoclonal Antibody MT103</other_name>
    <other_name>Blincyto</other_name>
    <other_name>MEDI-538</other_name>
    <other_name>MT-103</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cytarabine</intervention_name>
    <description>Given intrathecally via spinal tap</description>
    <arm_group_label>Treatment (blinatumomab, chemotherapy, ponatinib)</arm_group_label>
    <other_name>.beta.-Cytosine arabinoside</other_name>
    <other_name>1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone</other_name>
    <other_name>1-.beta.-D-Arabinofuranosylcytosine</other_name>
    <other_name>1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone</other_name>
    <other_name>1-Beta-D-arabinofuranosylcytosine</other_name>
    <other_name>1.beta.-D-Arabinofuranosylcytosine</other_name>
    <other_name>2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-</other_name>
    <other_name>2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-</other_name>
    <other_name>Alexan</other_name>
    <other_name>Ara-C</other_name>
    <other_name>ARA-cell</other_name>
    <other_name>Arabine</other_name>
    <other_name>Arabinofuranosylcytosine</other_name>
    <other_name>Arabinosylcytosine</other_name>
    <other_name>Aracytidine</other_name>
    <other_name>Aracytin</other_name>
    <other_name>Aracytine</other_name>
    <other_name>Beta-cytosine Arabinoside</other_name>
    <other_name>CHX-3311</other_name>
    <other_name>Cytarabinum</other_name>
    <other_name>Cytarbel</other_name>
    <other_name>Cytosar</other_name>
    <other_name>Cytosine Arabinoside</other_name>
    <other_name>Cytosine-.beta.-arabinoside</other_name>
    <other_name>Cytosine-beta-arabinoside</other_name>
    <other_name>Erpalfa</other_name>
    <other_name>Starasid</other_name>
    <other_name>Tarabine PFS</other_name>
    <other_name>U 19920</other_name>
    <other_name>U-19920</other_name>
    <other_name>Udicil</other_name>
    <other_name>WR-28453</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Methotrexate</intervention_name>
    <description>Given intrathecally via spinal tap</description>
    <arm_group_label>Treatment (blinatumomab, chemotherapy, ponatinib)</arm_group_label>
    <other_name>Abitrexate</other_name>
    <other_name>Alpha-Methopterin</other_name>
    <other_name>Amethopterin</other_name>
    <other_name>Brimexate</other_name>
    <other_name>CL 14377</other_name>
    <other_name>CL-14377</other_name>
    <other_name>Emtexate</other_name>
    <other_name>Emthexat</other_name>
    <other_name>Emthexate</other_name>
    <other_name>Farmitrexat</other_name>
    <other_name>Fauldexato</other_name>
    <other_name>Folex</other_name>
    <other_name>Folex PFS</other_name>
    <other_name>Lantarel</other_name>
    <other_name>Ledertrexate</other_name>
    <other_name>Lumexon</other_name>
    <other_name>Maxtrex</other_name>
    <other_name>Medsatrexate</other_name>
    <other_name>Metex</other_name>
    <other_name>Methoblastin</other_name>
    <other_name>Methotrexate LPF</other_name>
    <other_name>Methotrexate Methylaminopterin</other_name>
    <other_name>Methotrexatum</other_name>
    <other_name>Metotrexato</other_name>
    <other_name>Metrotex</other_name>
    <other_name>Mexate</other_name>
    <other_name>Mexate-AQ</other_name>
    <other_name>MTX</other_name>
    <other_name>Novatrex</other_name>
    <other_name>Rheumatrex</other_name>
    <other_name>Texate</other_name>
    <other_name>Tremetex</other_name>
    <other_name>Trexeron</other_name>
    <other_name>Trixilem</other_name>
    <other_name>WR-19039</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ponatinib</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (blinatumomab, chemotherapy, ponatinib)</arm_group_label>
    <other_name>AP-24534</other_name>
    <other_name>AP24534</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of one of the following:&#xD;
&#xD;
               -  Patients &gt;= 60 years of age with previously untreated Ph-positive ALL (either&#xD;
                  t(9;22) and/or BCR-ABL positive) (includes patients initiated on first course of&#xD;
                  therapy before cytogenetics known) or with lymphoid accelerated or blast phase&#xD;
                  chronic myelogenous leukemia (CML). These patients could have received one or two&#xD;
                  courses of chemotherapy with or without other tyrosine kinase inhibitors (TKIs)&#xD;
                  and still eligible. Patients &lt; 60 years of age may be enrolled if they are&#xD;
                  considered unfit for intensive chemotherapy: i) if they achieved CR, they are&#xD;
                  assessable only for event-free and overall survival; OR ii) If they failed to&#xD;
                  achieve CR, they are assessable for CR, event-free, and overall survival;&#xD;
&#xD;
               -  Patients &gt;= 18 years of age with relapsed / refractory Ph-positive ALL or with&#xD;
                  previously treated lymphoid accelerated or blast phase CML.&#xD;
&#xD;
          -  Performance status =&lt; 2 (Eastern Cooperative Oncology Group [ECOG] scale).&#xD;
&#xD;
          -  Total serum bilirubin =&lt; 2 x upper limit of normal (ULN), unless due to Gilbert's&#xD;
             syndrome (unless the increased values are judged to be leukemia disease related).&#xD;
&#xD;
          -  Alanine aminotransferase (ALT) =&lt; 3 x ULN (unless the increased values are judged to&#xD;
             be leukemia disease related).&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) =&lt; 3 x ULN (unless the increased values are judged to&#xD;
             be leukemia disease related).&#xD;
&#xD;
          -  Serum lipase and amylase =&lt; 1.5 x ULN.&#xD;
&#xD;
          -  For females of childbearing potential, a negative urine pregnancy test must be&#xD;
             documented.&#xD;
&#xD;
          -  Female patients who: are postmenopausal for at least 1 year before the screening&#xD;
             visit, OR are surgically sterile, OR If they are of childbearing potential, agree to&#xD;
             practice 2 effective methods of contraception, at the same time, from the time of&#xD;
             signing the informed consent through 4 months after the last dose of study drug, OR&#xD;
             agree to completely abstain from heterosexual intercourse.&#xD;
&#xD;
          -  Male patients, even if surgically sterilized (i.e., status post-vasectomy), who: agree&#xD;
             to practice effective barrier contraception during the entire study treatment period&#xD;
             and through 4 months after the last dose of study drug, OR agree to completely abstain&#xD;
             from heterosexual intercourse.&#xD;
&#xD;
          -  Adequate cardiac function as assessed clinically by history and physical examination.&#xD;
&#xD;
          -  Signed informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Active serious infection not controlled by oral or intravenous antibiotics.&#xD;
&#xD;
          -  History of acute pancreatitis within 1 year of study or history of chronic&#xD;
             pancreatitis.&#xD;
&#xD;
          -  History of alcohol abuse.&#xD;
&#xD;
          -  Uncontrolled hypertriglyceridemia (triglycerides &gt; 450 mg/dL).&#xD;
&#xD;
          -  Active secondary malignancy other than skin cancer (e.g., basal cell carcinoma or&#xD;
             squamous cell carcinoma) that in the investigator's opinion will shorten survival to&#xD;
             less than 1 year.&#xD;
&#xD;
          -  Active grade III-V cardiac failure as defined by the New York Heart Association&#xD;
             criteria.&#xD;
&#xD;
          -  Uncontrolled, or active cardiovascular disease, specifically including, but not&#xD;
             restricted to: myocardial infarction (MI), stroke, or revascularization within 3&#xD;
             months; unstable angina or transient ischemic attack; congestive heart failure prior&#xD;
             to enrollment, or left ventricular ejection fraction (LVEF) less than lower limit of&#xD;
             normal per local institutional standards prior to enrollment; diagnosed or suspected&#xD;
             congenital long QT syndrome; clinically significant atrial or ventricular arrhythmias&#xD;
             (such as atrial fibrillation, ventricular tachycardia, ventricular fibrillation, or&#xD;
             Torsades de pointes) as determined by the treating physician; prolonged corrected QT&#xD;
             (QTc) interval on pre-entry electrocardiogram (&gt; 470 msec) unless corrected after&#xD;
             electrolyte replacement or approved by cardiologist. Significant venous or arterial&#xD;
             thromboembolism including deep venous thrombosis or pulmonary embolism. Patients with&#xD;
             a history of treated prior superficial or catheter associated will not be considered&#xD;
             as significant embolism and after discussion with principal investigator (PI) will not&#xD;
             be excluded from eligibility; uncontrolled hypertension (diastolic blood pressure &gt; 90&#xD;
             mmHg; systolic &gt; 140 mmHg). Patients with hypertension should be under treatment on&#xD;
             study entry to effect blood pressure control.&#xD;
&#xD;
          -  Taking any medications or herbal supplements that are known to be strong inhibitors of&#xD;
             CYP3A4 within at least 14 days or 5 half-lives before the first dose of ponatinib in&#xD;
             patients with newly diagnosed only.&#xD;
&#xD;
          -  History or presence of clinically relevant central nervous system (CNS) pathology such&#xD;
             as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain&#xD;
             injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome,&#xD;
             or psychosis. Patients with active CNS leukemia will be excluded.&#xD;
&#xD;
          -  Current autoimmune disease or history of autoimmune disease with potential CNS&#xD;
             involvement.&#xD;
&#xD;
          -  Treatment with any investigational antileukemic agents or chemotherapy agents in the&#xD;
             last 7 days before study entry, unless full recovery from side effects has occurred or&#xD;
             patient has rapidly progressive disease judged to be life-threatening by the&#xD;
             investigator.&#xD;
&#xD;
          -  Pregnant and lactating women will not be eligible; women of childbearing potential&#xD;
             should have a negative urine pregnancy test prior to entering on the study and be&#xD;
             willing to practice methods of contraception. Women do not have childbearing potential&#xD;
             if they have had a hysterectomy or are postmenopausal without menses for 12 months. In&#xD;
             addition, men enrolled on this study should understand the risks to any sexual partner&#xD;
             of childbearing potential and should practice an effective method of birth control.&#xD;
&#xD;
          -  History of significant bleeding disorder unrelated to cancer, including: diagnosed&#xD;
             congenital bleeding disorders (e.g., von Willebrand's disease); diagnosed acquired&#xD;
             bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies).&#xD;
&#xD;
          -  Patients with documented significant pleural or pericardial effusions unless they are&#xD;
             thought to be secondary to their leukemia.&#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_official>
    <last_name>Elias Jabbour</last_name>
    <role>Principal Investigator</role>
    <affiliation>M.D. Anderson Cancer Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Elias Jabbour, MD</last_name>
    <phone>713-792-4764</phone>
    <email>ejabbour@mdanderson.org</email>
  </overall_contact>
  <location>
    <facility>
      <name>M D Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Elias Jabbour</last_name>
      <phone>713-792-4764</phone>
      <email>ejabbour@mdanderson.org</email>
    </contact>
    <investigator>
      <last_name>Elias Jabbour</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mdanderson.org</url>
    <description>University of Texas MD Anderson Cancer Center</description>
  </link>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>August 24, 2017</study_first_submitted>
  <study_first_submitted_qc>August 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 28, 2017</study_first_posted>
  <last_update_submitted>September 6, 2023</last_update_submitted>
  <last_update_submitted_qc>September 6, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 8, 2023</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>Leukemia, Myeloid</mesh_term>
    <mesh_term>Leukemia, Myelogenous, Chronic, BCR-ABL Positive</mesh_term>
    <mesh_term>Leukemia, Myeloid, Accelerated Phase</mesh_term>
    <mesh_term>Blast Crisis</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>Cytarabine</mesh_term>
    <mesh_term>Antineoplastic Agents, Immunological</mesh_term>
    <mesh_term>Methotrexate</mesh_term>
    <mesh_term>Blinatumomab</mesh_term>
    <mesh_term>Ponatinib</mesh_term>
    <mesh_term>Antibodies</mesh_term>
    <mesh_term>Immunoglobulins</mesh_term>
    <mesh_term>Antibodies, Monoclonal</mesh_term>
    <mesh_term>Muromonab-CD3</mesh_term>
    <mesh_term>Antibodies, Bispecific</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/NCT03263572
org study id: 2016-0792
secondary id: NCI-2018-01078
secondary id: 2016-0792
nct id: NCT03263572
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This phase II trial studies how well blinatumomab, methotrexate, cytarabine, and ponatinib
      work in treating patients with Philadelphia chromosome (Ph)-positive, or BCR-ABL positive, or
      acute lymphoblastic leukemia that has come back or does not respond to treatment.
      Immunotherapy with monoclonal antibodies, such as blinatumomab, may induce changes in body's
      immune system and may interfere with the ability of tumor cells to grow and spread. Drugs
      used in chemotherapy, such as methotrexate and cytarabine, work in different ways to stop the
      growth of cancer cells, either by killing the cells, by stopping them from dividing, or by
      stopping them from spreading. Ponatinib may stop the growth of cancer cells by blocking some
      of the enzymes needed for cell growth. Giving blinatumomab, methotrexate, cytarabine, and
      ponatinib may work better in treating patients with acute lymphoblastic leukemia.
PRIMARY OBJECTIVES:

      I. To evaluate the complete molecular response rate in cohort 1 (newly diagnosed Philadelphia
      chromosome [Ph-positive] and/or BCR-ABL-positive acute lymphoblastic leukemia [ALL]) and the
      overall response (complete remission [CR]+CR with incomplete blood count recovery [CRi]) rate
      in cohort 2 (relapsed/refractory disease).

      SECONDARY OBJECTIVES:

      I. To evaluate other clinical efficacy endpoints (complete cytogenetic response, complete
      molecular response [CMR], event-free survival [EFS] and overall survival [OS]) and safety of
      the regimen.

      EXPLORATORY OBJECTIVES:

      I. To characterize the role of ABL1 kinase domain mutations on treatment failure and relapse
      in patients with Ph+ ALL treated with blinatumomab plus ponatinib.

      II. To determine the impact of recurrent genomic alterations and ribonucleic acid (RNA)
      expression at diagnosis on relapse-free survival (RFS) in patients with Ph+ ALL treated with
      blinatumomab plus ponatinib.

      III. To investigate the impact of next-generation sequencing-based minimal residual disease
      assessment on relapse-free survival in patients with Ph+ ALL.

      IV. To determine the effect on immune cell subsets in patients with Ph+ ALL treated with
      blinatumomab plus ponatinib.

      OUTLINE:

      Patients receive blinatumomab intravenously (IV) nonstop on days 1-28 of cycles 1-5, and
      methotrexate and cytarabine intrathecally (by spinal tap) on days 1, 15, and 29 of cycles
      1-4. Patients also receive ponatinib orally (PO) daily. Cycles repeat every 6 weeks in the
      absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 30 days and every 6 months
      thereafter.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Complete molecular response (CMR) rate in newly diagnosed Ph-positive and/or BCR-ABL-positive acute lymphoblastic leukemia (ALL)
time frame: At 18 weeks
measure: Overall response rate (ORR) in relapsed/refractory ALL
time frame: At 12 weeks
description: This is defined as the percentage of patients achieving complete remission (CR) or CR with incomplete blood count recovery (CRi).
measure: Relapse-free survival
time frame: From documented complete response until relapse or death, assessed up to 6 years
measure: Event-free survival
time frame: From first day of treatment until any failure (resistant disease, relapse, or death), assessed up to 6 years
measure: Overall survival
time frame: First day of treatment to time of death from any cause, assessed up to 6 years
arm group label: Treatment (blinatumomab, chemotherapy, ponatinib)
arm group type: Experimental
description: Patients receive blinatumomab IV nonstop on days 1-28 of cycles 1-5, and methotrexate and cytarabine intrathecally (by spinal tap) on days 1, 15, and 29 of cycles 1-4. Patients also receive ponatinib PO daily. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
intervention type: Biological
intervention name: Blinatumomab
description: Given IV
arm group label: Treatment (blinatumomab, chemotherapy, ponatinib)
other name: Anti-CD19 x Anti-CD3 Bispecific Monoclonal Antibody
other name: Anti-CD19/Anti-CD3 Recombinant Bispecific Monoclonal Antibody MT103
other name: Blincyto
other name: MEDI-538
other name: MT-103
intervention type: Drug
intervention name: Cytarabine
description: Given intrathecally via spinal tap
arm group label: Treatment (blinatumomab, chemotherapy, ponatinib)
other name: .beta.-Cytosine arabinoside
other name: 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone
other name: 1-.beta.-D-Arabinofuranosylcytosine
other name: 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone
other name: 1-Beta-D-arabinofuranosylcytosine
other name: 1.beta.-D-Arabinofuranosylcytosine
other name: 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-
other name: 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-
other name: Alexan
other name: Ara-C
other name: ARA-cell
other name: Arabine
other name: Arabinofuranosylcytosine
other name: Arabinosylcytosine
other name: Aracytidine
other name: Aracytin
other name: Aracytine
other name: Beta-cytosine Arabinoside
other name: CHX-3311
other name: Cytarabinum
other name: Cytarbel
other name: Cytosar
other name: Cytosine Arabinoside
other name: Cytosine-.beta.-arabinoside
other name: Cytosine-beta-arabinoside
other name: Erpalfa
other name: Starasid
other name: Tarabine PFS
other name: U 19920
other name: U-19920
other name: Udicil
other name: WR-28453
intervention type: Drug
intervention name: Methotrexate
description: Given intrathecally via spinal tap
arm group label: Treatment (blinatumomab, chemotherapy, ponatinib)
other name: Abitrexate
other name: Alpha-Methopterin
other name: Amethopterin
other name: Brimexate
other name: CL 14377
other name: CL-14377
other name: Emtexate
other name: Emthexat
other name: Emthexate
other name: Farmitrexat
other name: Fauldexato
other name: Folex
other name: Folex PFS
other name: Lantarel
other name: Ledertrexate
other name: Lumexon
other name: Maxtrex
other name: Medsatrexate
other name: Metex
other name: Methoblastin
other name: Methotrexate LPF
other name: Methotrexate Methylaminopterin
other name: Methotrexatum
other name: Metotrexato
other name: Metrotex
other name: Mexate
other name: Mexate-AQ
other name: MTX
other name: Novatrex
other name: Rheumatrex
other name: Texate
other name: Tremetex
other name: Trexeron
other name: Trixilem
other name: WR-19039
intervention type: Drug
intervention name: Ponatinib
description: Given PO
arm group label: Treatment (blinatumomab, chemotherapy, ponatinib)
other name: AP-24534
other name: AP24534
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Elias Jabbour
role: Principal Investigator
affiliation: M.D. Anderson Cancer Center
last name: Elias Jabbour, MD
phone: 713-792-4764
email: ejabbour@mdanderson.org
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
url: http://www.mdanderson.org
description: University of Texas MD Anderson Cancer Center
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Leukemia, Lymphoid
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myelogenous, Chronic, BCR-ABL Positive
mesh term: Leukemia, Myeloid, Accelerated Phase
mesh term: Blast Crisis
mesh term: Philadelphia Chromosome
mesh term: Cytarabine
mesh term: Antineoplastic Agents, Immunological
mesh term: Methotrexate
mesh term: Blinatumomab
mesh term: Ponatinib
mesh term: Antibodies
mesh term: Immunoglobulins
mesh term: Antibodies, Monoclonal
mesh term: Muromonab-CD3
mesh term: Antibodies, Bispecific