<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/NCT03817320</url>
  </required_header>
  <id_info>
    <org_study_id>T2017-002</org_study_id>
    <nct_id>NCT03817320</nct_id>
  </id_info>
  <brief_title>PO Ixazomib in Combination With Chemotherapy for Childhood Relapsed or Refractory Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma</brief_title>
  <official_title>A TACL Phase 1/2 Study of PO Ixazomib in Combination With Chemotherapy for Childhood Relapsed or Refractory Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma IND# 140730</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Therapeutic Advances in Childhood Leukemia Consortium</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Takeda</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Children's Hospital Los Angeles</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Therapeutic Advances in Childhood Leukemia Consortium</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 is a phase 1/2 study of a drug called Ixazomib in combination with cytotoxic&#xD;
      chemotherapy consisting of Vincristine, Dexamethasone, Asparaginase, and Doxorubicin (VXLD).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The phase 1 study is to determine the maximum tolerated dose (MTD) of the PO formulation,&#xD;
      followed by a screening phase 2 study to investigate the efficacy of ixazomib in combination&#xD;
      with chemotherapy in children with relapsed ALL and lymphoblastic lymphoma (LLy). The single&#xD;
      arm, screening phase 2 design will allow us to use a minimal number of patients to obtain&#xD;
      preliminary information about treatment efficacy. Discovering a safe and tolerable dose of&#xD;
      ixazomib in a PO formulation and the preliminary efficacy data will significantly increase&#xD;
      the possibility of ixazomib moving forward in frontline pediatric treatment protocols in both&#xD;
      intense chemotherapy courses and maintenance courses.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">February 12, 2019</start_date>
  <completion_date type="Anticipated">June 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</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>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Phase 1: Dose limiting toxicity (DLT) during block 1 of chemotherapy</measure>
    <time_frame>5 weeks</time_frame>
    <description>The incidence of dose limiting toxicity (DLT) will be measured only during block 1</description>
  </primary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">31</enrollment>
  <condition>ALL, Childhood</condition>
  <condition>Lymphoblastic Lymphoma, Childhood</condition>
  <condition>Lymphoblastic Leukemia, Acute, Childhood</condition>
  <arm_group>
    <arm_group_label>Ixazomib Dose Level 1 (Stratum A)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will be treated on ixazomib at 1.6 mg/m^2/day on Days 1, 4, 8, and 11. Vincristine IV at 1.5 mg/m^2 on Days 1, 8, 15 and 22. Pegaspargase IV/IM at 2500 IU/m^2 on Days 2 and 15, Doxorubicin at 60 mg/m^2 on Days 1, Dexamethasone IV/PO at 10 mg/m^2 continuous starting on Day 1 thru Day 14, and IT chemotherapy dependent on patient's CNS status at time of enrollment. This arm is the starting Dose Level for patients being enrolled.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ixazomib Dose Level 2 (Stratum A)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will be treated on ixazomib at 2.0 mg/m^2/day on Days 1, 4, 8, and 11. Vincristine IV at 1.5 mg/m^2 on Days 1, 8, 15 and 22. Pegaspargase IV/IM at 2500 IU/m^2 on Days 2 and 15, Doxorubicin at 60 mg/m^2 on Days 1, Dexamethasone IV/PO at 10 mg/m^2 continuous starting on Day 1 thru Day 14, and IT chemotherapy dependent on patient's CNS status at time of enrollment. Patients will be treated at this arm Dose Level once patient accrual at Dose Level 1 has been completed and dose escalation is allowed as defined by the 3+3 design.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ixazomib Dose Level -1 (Stratum A)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will be treated on ixazomib at 1.2 mg/m^2/day on Days 1, 4, 8, and 11. Vincristine IV at 1.5 mg/m^2 on Days 1, 8, 15 and 22. Pegaspargase IV/IM at 2500 IU/m^2 on Days 2 and 15, Doxorubicin at 60 mg/m^2 on Days 1, Dexamethasone IV/PO at 10 mg/m^2 continuous starting on Day 1 thru Day 14, and IT chemotherapy dependent on patient's CNS status at time of enrollment. This arm Dose Level -1 is needed only if de-escalation from Dose Level 1 is required.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ixazomib Dose Level 1 (Stratum B)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will be treated on ixazomib at 1.6 mg/m^2/day on Days 1, 4, 8, and 11. Vincristine IV at 1.5 mg/m^2 on Days 1, 8, 15 and 22. Pegaspargase IV/IM at 2500 IU/m^2 on Days 2 and 15, Doxorubicin at 60 mg/m^2 on Days 1, Dexamethasone IV/PO at 10 mg/m^2 continuous starting on Day 1 thru Day 14, and IT chemotherapy dependent on patient's CNS status at time of enrollment. Leucovorin PO/IV at 5 mg/m^2/dose X 2 doses given 24 and 30 hours after IT Methotrexate or Triple IT will also be given on this arm. This arm is only for patients with Down syndrome (Stratum B).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ixazomib</intervention_name>
    <description>Days 1, 4, 8, and 11. Note: at least 72 hours must have elapsed between doses&#xD;
Dose Phase 1 - Assigned upon study entry.&#xD;
Phase 2 - PO formulation at RP2D</description>
    <arm_group_label>Ixazomib Dose Level -1 (Stratum A)</arm_group_label>
    <arm_group_label>Ixazomib Dose Level 1 (Stratum A)</arm_group_label>
    <arm_group_label>Ixazomib Dose Level 1 (Stratum B)</arm_group_label>
    <arm_group_label>Ixazomib Dose Level 2 (Stratum A)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vincristine</intervention_name>
    <description>IV push over 1 minute or infusion via minibag as per institutional policy&#xD;
Days 1, 8, 15 and 22&#xD;
Dose: ≥ 1 year: 1.5mg/m2/dose (maximum dose 2mg)&#xD;
≥ 6 months and &lt; 1 year: 1.2mg/m2/dose&#xD;
&lt; 6 months: 1mg/m2/dose</description>
    <arm_group_label>Ixazomib Dose Level -1 (Stratum A)</arm_group_label>
    <arm_group_label>Ixazomib Dose Level 1 (Stratum A)</arm_group_label>
    <arm_group_label>Ixazomib Dose Level 1 (Stratum B)</arm_group_label>
    <arm_group_label>Ixazomib Dose Level 2 (Stratum A)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexamethasone</intervention_name>
    <description>Days 1-14&#xD;
Dose: ≥ 1 year: 10mg/m2/day, divided BID (i.e., 5mg/m2/dose, BID)&#xD;
≥ 6 months and &lt; 1 year: 8mg/m2/day, divided BID (i.e., 4 mg/m2/dose, BID)&#xD;
&lt; 6 months: 7mg/m2/day, divided BID (i.e., 3.5 mg/m2/dose, BID)</description>
    <arm_group_label>Ixazomib Dose Level -1 (Stratum A)</arm_group_label>
    <arm_group_label>Ixazomib Dose Level 1 (Stratum A)</arm_group_label>
    <arm_group_label>Ixazomib Dose Level 1 (Stratum B)</arm_group_label>
    <arm_group_label>Ixazomib Dose Level 2 (Stratum A)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Asparaginase</intervention_name>
    <description>Days 2, 15&#xD;
Dose ≥ 1 year: 2,500 International units (IU)/m2/dose&#xD;
≥ 6 months and &lt; 1 year: 2,000 IU/m2/dose&#xD;
&lt; 6 months: 1,750 IU/m2/dose&#xD;
Patient with allergic reaction to Pegaspargase can be given Erwinase IM/IV on Mon/Wed/Fri (or every other day per institutional standard) x 6 doses for each dose of Pegaspargase.&#xD;
Dosing guideline for Erwinase:&#xD;
1 year: 25,000 IU/m2/dose&#xD;
6 months and &lt; 1 year: 20,000 IU/m2/dose&#xD;
&lt; 6 months: 17,500 IU/m2/dose</description>
    <arm_group_label>Ixazomib Dose Level -1 (Stratum A)</arm_group_label>
    <arm_group_label>Ixazomib Dose Level 1 (Stratum A)</arm_group_label>
    <arm_group_label>Ixazomib Dose Level 1 (Stratum B)</arm_group_label>
    <arm_group_label>Ixazomib Dose Level 2 (Stratum A)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Doxorubicin</intervention_name>
    <description>Day 1&#xD;
Dose ≥ 1 year: 60mg/m2/dose&#xD;
≥ 6 months and &lt; 1 year: 48 mg/m2/dose&#xD;
&lt; 6 months: 42mg/m2/dose</description>
    <arm_group_label>Ixazomib Dose Level -1 (Stratum A)</arm_group_label>
    <arm_group_label>Ixazomib Dose Level 1 (Stratum A)</arm_group_label>
    <arm_group_label>Ixazomib Dose Level 1 (Stratum B)</arm_group_label>
    <arm_group_label>Ixazomib Dose Level 2 (Stratum A)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Methotrexate (IT)</intervention_name>
    <description>For patients with CNS 1 or CNS 2, on Days 1, 15, and 29</description>
    <arm_group_label>Ixazomib Dose Level -1 (Stratum A)</arm_group_label>
    <arm_group_label>Ixazomib Dose Level 1 (Stratum A)</arm_group_label>
    <arm_group_label>Ixazomib Dose Level 1 (Stratum B)</arm_group_label>
    <arm_group_label>Ixazomib Dose Level 2 (Stratum A)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Triple IT (Methotrexate, Hydrocortisone, Cytarabine)</intervention_name>
    <description>For patients with CNS 3, on Days 1, 8, 15, 22, and 29</description>
    <arm_group_label>Ixazomib Dose Level -1 (Stratum A)</arm_group_label>
    <arm_group_label>Ixazomib Dose Level 1 (Stratum A)</arm_group_label>
    <arm_group_label>Ixazomib Dose Level 1 (Stratum B)</arm_group_label>
    <arm_group_label>Ixazomib Dose Level 2 (Stratum A)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Leucovorin</intervention_name>
    <description>For patients with Down syndrome only, on Days 2, 9, 16, 23, and 30 (based on dates when IT Methotrexate or Triple IT is given)</description>
    <arm_group_label>Ixazomib Dose Level 1 (Stratum B)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age Patients must be ≤21 years of age at the time of enrollment.&#xD;
&#xD;
               1. Phase 1 - Initial enrollment will be restricted to patients &lt; 18 years of age&#xD;
                  until 9 such patients are enrolled&#xD;
&#xD;
               2. Phase 2 - Initial enrollment will be restricted to patients &lt; 18 years of age&#xD;
                  until 6 such patients are enrolled (applies to Stratum A only)&#xD;
&#xD;
          -  Diagnosis Patients must have a diagnosis of relapsed/refractory ALL or LLy with or&#xD;
             without extramedullary disease (including CNS2 and CNS3). Patient with mixed phenotype&#xD;
             ALL or mature B (Burkitt-like) leukemia are not eligible.&#xD;
&#xD;
               1. Patients with ALL must have ≥ 5% blasts by morphology.&#xD;
&#xD;
               2. Patients with LLy must have measurable disease documented by clinical, radiologic&#xD;
                  or histologic criteria&#xD;
&#xD;
          -  Performance Level Karnofsky ≥ 50% for patients &gt; 16 years of age and Lansky ≥ 50% for&#xD;
             patients ≤ 16 years of age.&#xD;
&#xD;
          -  Prior Therapy A. Prior therapeutic attempts&#xD;
&#xD;
               -  Phase 1 - Any patients with relapsed/refractory ALL or LLy&#xD;
&#xD;
               -  Phase 2&#xD;
&#xD;
                    1. B-cell ALL/LLy: all patients must have failed two or more therapeutic&#xD;
                       attempts.&#xD;
&#xD;
                    2. T-cell ALL/LLy: all patients must have failed one or more therapeutic&#xD;
                       attempts. B. Recent prior chemotherapy Patients must have fully recovered&#xD;
                       from the acute toxic effects of all prior chemotherapy, immunotherapy, or&#xD;
                       radiotherapy prior to entering this study.&#xD;
&#xD;
               -  Myelosuppressive chemotherapy: At least 14 days must have elapsed since the&#xD;
                  completion of myelosuppressive therapy. However, patients may receive any of the&#xD;
                  following medications within 14 days without a &quot;wash-out&quot; period:&#xD;
&#xD;
          -  Hydroxyurea: Hydroxyurea can be initiated and/or continued for up to 24 hours prior to&#xD;
             the start of protocol therapy.&#xD;
&#xD;
               -  &quot;Maintenance-style&quot; therapy - Therapy including vincristine (dosed at a maximum&#xD;
                  of one-time weekly), oral 6-mercaptopurine, oral methotrexate (dosed at a maximum&#xD;
                  of one-time weekly), dexamethasone (dosed at ≤ 3 mg*/m^2/dose twice daily), and&#xD;
                  prednisone (dosed at ≤ 20 mg*/m^2/dose twice daily) can be initiated and/or&#xD;
                  continued for up to 24 hours prior to the start of protocol therapy.&#xD;
&#xD;
                    -  Doses can be rounded to adjust for pill size&#xD;
&#xD;
        C. Hematopoietic stem cell transplant: Patients who have experienced their relapse after a&#xD;
        HSCT are eligible, provided they have no evidence of acute or chronic Graft-versus-Host&#xD;
        Disease (GVHD), are not receiving GVHD prophylaxis or treatment, and are at least 90 days&#xD;
        post-transplant at the time of enrollment.&#xD;
&#xD;
        D. Hematopoietic growth factors: It must have been at least 7 days since the completion of&#xD;
        therapy with G-CSF or other growth factors at the time of enrollment. It must have been at&#xD;
        least 14 days since the completion of therapy with long-acting filgrastim (pegfilgrastim or&#xD;
        biosimilar)&#xD;
&#xD;
        E. Biologic (anti-neoplastic agent): At least 7 days since the last dose of a biologic&#xD;
        agent. For agents that have known adverse events occurring beyond 7 days after&#xD;
        administration, this period must be extended beyond the time during which adverse events&#xD;
        are known to occur. The duration of this interval must be discussed with the study chair&#xD;
&#xD;
          1. Monoclonal antibodies: At least 3 half-lives of the antibody or 21 days (whichever is&#xD;
             shorter) must have elapsed after the last dose of monoclonal antibody. (i.e.,&#xD;
             blinatumomab half-life = 6 hours, therefore washout is 18 hours; inotuzumab half-life&#xD;
             = 37 days therefore washout is 21 days; rituximab half-life = 66 days, therefore&#xD;
             washout is 21 days). If steroids are being used to modify immune-related adverse&#xD;
             events of antibody therapy, at least 14 days must have elapsed since the last dose of&#xD;
             corticosteroid.&#xD;
&#xD;
          2. Immunotherapy: At least 30 days after the completion of any type of immunotherapy,&#xD;
             e.g., tumor vaccines, CAR T cells. If steroids are being used to modify immune-related&#xD;
             adverse events of immunotherapy, at least 14 days must have elapsed since the last&#xD;
             dose of corticosteroid.&#xD;
&#xD;
        F. XRT: Craniospinal XRT is prohibited during protocol therapy. No washout period is&#xD;
        necessary for radiation given to any extramedullary site other than CNS; ≥90 days must have&#xD;
        elapsed if prior total body irradiation (TBI) or craniospinal XRT.&#xD;
&#xD;
        G. Anthracyclines: Patients must have had a lifetime exposure of &lt;400 mg/m^2 of doxorubicin&#xD;
        equivalents of anthracyclines.&#xD;
&#xD;
        H. Proteasome inhibitors: Patients with a prior exposure to proteasome inhibitors (e.g.,&#xD;
        bortezomib, carfilzomib) are eligible as long as the patient demonstrated at least a&#xD;
        partial response to a proteasome inhibitor with chemotherapy combination. This criteria&#xD;
        only applies to the Phase 2 portion of the study.&#xD;
&#xD;
        -Renal and hepatic function&#xD;
&#xD;
        Patients must have adequate renal and hepatic functions as indicated by the following&#xD;
        laboratory values:&#xD;
&#xD;
        A. Adequate renal function defined as: Patient must have a calculated creatinine clearance&#xD;
        or radioisotope GFR ≥ 70ml/min/1.73m^2 OR a normal serum creatinine based on age/gender&#xD;
&#xD;
        B. Adequate Liver Function Defined as: Direct bilirubin ≤ 1.5 x upper limit of normal (ULN)&#xD;
        for age or normal (except in the presence of Gilbert's syndrome), AND alanine transaminase&#xD;
        (ALT) ≤ 5 x ULN for age. The hepatic requirements are waived for patients with known or&#xD;
        suspected liver involvement by leukemia or lymphoma. This must be reviewed by and approved&#xD;
        by the study chair or vice chair.&#xD;
&#xD;
          -  Adequate Cardiac Function Defined as: Shortening fraction of ≥ 27% by echocardiogram,&#xD;
             OR ejection fraction of ≥ 50% by radionuclide angiogram (MUGA).&#xD;
&#xD;
          -  Reproductive Function A. Female patients of childbearing potential must have a&#xD;
             negative urine or serum pregnancy test confirmed within 2 weeks prior to enrollment.&#xD;
&#xD;
        B. Female patients with infants must agree not to breastfeed their infants while on this&#xD;
        study.&#xD;
&#xD;
        C. Male and female patients of child-bearing potential must agree to use an effective&#xD;
        method of contraception approved by the investigator during the study and for a minimum of&#xD;
        6 months after study treatment.&#xD;
&#xD;
          -  Informed Consent Patients and/or their parents or legal guardians must be capable of&#xD;
             understanding the investigational nature, potential risks and benefits of the study.&#xD;
             All patients and/or their parents or legal guardians must sign a written informed&#xD;
             consent. Age appropriate assent will be obtained per institutional guidelines. To&#xD;
             allow non-English speaking patients to participate in this study, bilingual health&#xD;
             services will be provided in the appropriate language when feasible.&#xD;
&#xD;
          -  All institutional, FDA, and OHRP requirements for human studies must be met.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Patients will be excluded if they have isolated CNS or testicular disease.&#xD;
&#xD;
        Patients will be excluded if they have ≥ grade 2 peripheral sensory or motor neuropathy&#xD;
        (defined by the Modified &quot;Balis&quot; Pediatric Scale of Pediatric Neuropathies) at the time of&#xD;
        enrollment.&#xD;
&#xD;
        Patients will be excluded if they have a known allergy or intolerance to any of the drugs&#xD;
        used in the study - except for Pegaspargase for which asparaginase Erwinia chrysanthemi&#xD;
        (recombinant)-rywn (Rylaze®) or (if available) crisantaspase (Erwinase®), may be&#xD;
        substituted for allergy to Pegaspargase&#xD;
&#xD;
        Patients will be excluded if they have a systemic fungal, bacterial, viral or other&#xD;
        infection that is exhibiting ongoing signs/symptoms related to the infection without&#xD;
        improvement despite appropriate antibiotics or other treatment. The patient needs to be off&#xD;
        pressors and have negative blood cultures for 48 hours.&#xD;
&#xD;
        Patients will be excluded if there is a plan to administer non-protocol chemotherapy,&#xD;
        radiation therapy, or immunotherapy during the study period.&#xD;
&#xD;
        Patients will be excluded if they have significant concurrent disease, illness, psychiatric&#xD;
        disorder or social issue that would compromise patient safety or compliance with the&#xD;
        protocol treatment or procedures, interfere with consent, study participation, follow up,&#xD;
        or interpretation of study results.&#xD;
&#xD;
        Patients with DNA fragility syndromes (such as Fanconi anemia, Bloom syndrome) are&#xD;
        excluded.&#xD;
&#xD;
        Patients will be excluded if they have had a lifetime exposure of ≥400 mg/m2 doxorubicin&#xD;
        equivalents of anthracyclines (anthracycline equivalence to doxorubicin conversion see&#xD;
        appendix iv) .&#xD;
&#xD;
        Concomitant medications Investigational drugs: Patients currently receiving another&#xD;
        investigational drug are not eligible.&#xD;
&#xD;
        Anti-GVHD agents post transplant: patients who are receiving cyclosporine, tacrolimus or&#xD;
        other agents to prevent graft-versus-host disease post hematopoetic stem cell transplant&#xD;
        are not eligible.&#xD;
&#xD;
        CYP3A4 agents: patients who are currently receiving drugs that are strong inducers of&#xD;
        CYP3A4 are not eligible.&#xD;
&#xD;
        Patients with Ph+ALL and Ph-like ALL who are currently receiving TKI therapy&#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>Terzah Horton, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Baylor College of Medicine</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Roy Leong</last_name>
    <phone>323-361-5132</phone>
    <email>rleong@chla.usc.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Benjamin Brookhart</last_name>
    <phone>323-361-5429</phone>
    <email>bbrookhart@chla.usc.edu</email>
  </overall_contact_backup>
  <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>Winston Huh, M.D.</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Children's Hospital Orange County</name>
      <address>
        <city>Orange</city>
        <state>California</state>
        <zip>92868</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Van Huynh, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Children's National Medical Center</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20010</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Reuven Schore, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>University of Miami</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Julio Barredo, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Children's Healthcare of Atlanta</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Melinda Pauly, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>C.S. Mott Children's Hospital</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Rajen Mody, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Children's Hospital and Clinics of Minnesota</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55404</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nathan Gossai, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Columbia University Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nobuko Hijiya, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Levine Cancer Institute</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28204</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Joel Kaplan, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>University Hospitals Seidman Cancer Center</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Rachel Egler, MD</last_name>
    </contact>
  </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>Susan Colace, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Doernbecher Children's Hospital</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Bill Chang, MD</last_name>
    </contact>
  </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>Susan Rheingold, MD</last_name>
    </contact>
  </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>Jeffrey Rubnitz, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>University of Texas, Southwestern</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75235</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Tamra Slone, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Cook Children's Medical Center</name>
      <address>
        <city>Fort Worth</city>
        <state>Texas</state>
        <zip>76104</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kenneth Heym, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Texas Children's Hospital/Baylor University</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Eric Schafer, MD</last_name>
    </contact>
    <contact_backup>
      <last_name>Terzah Horton, MD</last_name>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>The Children's Hospital at Westmead</name>
      <address>
        <city>Westmead</city>
        <state>New South Wales</state>
        <zip>2145</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Luciano Dalla-Pozza, MD</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>January 22, 2019</study_first_submitted>
  <study_first_submitted_qc>January 24, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 25, 2019</study_first_posted>
  <last_update_submitted>August 11, 2022</last_update_submitted>
  <last_update_submitted_qc>August 11, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 15, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</mesh_term>
    <mesh_term>Leukemia, Lymphoid</mesh_term>
    <mesh_term>Lymphoma, Non-Hodgkin</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leucovorin</mesh_term>
    <mesh_term>Cytarabine</mesh_term>
    <mesh_term>Dexamethasone</mesh_term>
    <mesh_term>Hydrocortisone</mesh_term>
    <mesh_term>Doxorubicin</mesh_term>
    <mesh_term>Methotrexate</mesh_term>
    <mesh_term>Vincristine</mesh_term>
    <mesh_term>Asparaginase</mesh_term>
    <mesh_term>Ixazomib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT03817320
org study id: T2017-002
nct id: NCT03817320
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a phase 1/2 study of a drug called Ixazomib in combination with cytotoxic
      chemotherapy consisting of Vincristine, Dexamethasone, Asparaginase, and Doxorubicin (VXLD).
The phase 1 study is to determine the maximum tolerated dose (MTD) of the PO formulation,
      followed by a screening phase 2 study to investigate the efficacy of ixazomib in combination
      with chemotherapy in children with relapsed ALL and lymphoblastic lymphoma (LLy). The single
      arm, screening phase 2 design will allow us to use a minimal number of patients to obtain
      preliminary information about treatment efficacy. Discovering a safe and tolerable dose of
      ixazomib in a PO formulation and the preliminary efficacy data will significantly increase
      the possibility of ixazomib moving forward in frontline pediatric treatment protocols in both
      intense chemotherapy courses and maintenance courses.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Phase 1: Dose limiting toxicity (DLT) during block 1 of chemotherapy
time frame: 5 weeks
description: The incidence of dose limiting toxicity (DLT) will be measured only during block 1
arm group label: Ixazomib Dose Level 1 (Stratum A)
arm group type: Experimental
description: Patients will be treated on ixazomib at 1.6 mg/m^2/day on Days 1, 4, 8, and 11. Vincristine IV at 1.5 mg/m^2 on Days 1, 8, 15 and 22. Pegaspargase IV/IM at 2500 IU/m^2 on Days 2 and 15, Doxorubicin at 60 mg/m^2 on Days 1, Dexamethasone IV/PO at 10 mg/m^2 continuous starting on Day 1 thru Day 14, and IT chemotherapy dependent on patient's CNS status at time of enrollment. This arm is the starting Dose Level for patients being enrolled.
arm group label: Ixazomib Dose Level 2 (Stratum A)
arm group type: Experimental
description: Patients will be treated on ixazomib at 2.0 mg/m^2/day on Days 1, 4, 8, and 11. Vincristine IV at 1.5 mg/m^2 on Days 1, 8, 15 and 22. Pegaspargase IV/IM at 2500 IU/m^2 on Days 2 and 15, Doxorubicin at 60 mg/m^2 on Days 1, Dexamethasone IV/PO at 10 mg/m^2 continuous starting on Day 1 thru Day 14, and IT chemotherapy dependent on patient's CNS status at time of enrollment. Patients will be treated at this arm Dose Level once patient accrual at Dose Level 1 has been completed and dose escalation is allowed as defined by the 3+3 design.
arm group label: Ixazomib Dose Level -1 (Stratum A)
arm group type: Experimental
description: Patients will be treated on ixazomib at 1.2 mg/m^2/day on Days 1, 4, 8, and 11. Vincristine IV at 1.5 mg/m^2 on Days 1, 8, 15 and 22. Pegaspargase IV/IM at 2500 IU/m^2 on Days 2 and 15, Doxorubicin at 60 mg/m^2 on Days 1, Dexamethasone IV/PO at 10 mg/m^2 continuous starting on Day 1 thru Day 14, and IT chemotherapy dependent on patient's CNS status at time of enrollment. This arm Dose Level -1 is needed only if de-escalation from Dose Level 1 is required.
arm group label: Ixazomib Dose Level 1 (Stratum B)
arm group type: Experimental
description: Patients will be treated on ixazomib at 1.6 mg/m^2/day on Days 1, 4, 8, and 11. Vincristine IV at 1.5 mg/m^2 on Days 1, 8, 15 and 22. Pegaspargase IV/IM at 2500 IU/m^2 on Days 2 and 15, Doxorubicin at 60 mg/m^2 on Days 1, Dexamethasone IV/PO at 10 mg/m^2 continuous starting on Day 1 thru Day 14, and IT chemotherapy dependent on patient's CNS status at time of enrollment. Leucovorin PO/IV at 5 mg/m^2/dose X 2 doses given 24 and 30 hours after IT Methotrexate or Triple IT will also be given on this arm. This arm is only for patients with Down syndrome (Stratum B).
intervention type: Drug
intervention name: Ixazomib
description: Days 1, 4, 8, and 11. Note: at least 72 hours must have elapsed between doses
Dose Phase 1 - Assigned upon study entry.
Phase 2 - PO formulation at RP2D
arm group label: Ixazomib Dose Level -1 (Stratum A)
arm group label: Ixazomib Dose Level 1 (Stratum A)
arm group label: Ixazomib Dose Level 1 (Stratum B)
arm group label: Ixazomib Dose Level 2 (Stratum A)
intervention type: Drug
intervention name: Vincristine
description: IV push over 1 minute or infusion via minibag as per institutional policy
Days 1, 8, 15 and 22
Dose: ≥ 1 year: 1.5mg/m2/dose (maximum dose 2mg)
≥ 6 months and < 1 year: 1.2mg/m2/dose
< 6 months: 1mg/m2/dose
arm group label: Ixazomib Dose Level -1 (Stratum A)
arm group label: Ixazomib Dose Level 1 (Stratum A)
arm group label: Ixazomib Dose Level 1 (Stratum B)
arm group label: Ixazomib Dose Level 2 (Stratum A)
intervention type: Drug
intervention name: Dexamethasone
description: Days 1-14
Dose: ≥ 1 year: 10mg/m2/day, divided BID (i.e., 5mg/m2/dose, BID)
≥ 6 months and < 1 year: 8mg/m2/day, divided BID (i.e., 4 mg/m2/dose, BID)
< 6 months: 7mg/m2/day, divided BID (i.e., 3.5 mg/m2/dose, BID)
arm group label: Ixazomib Dose Level -1 (Stratum A)
arm group label: Ixazomib Dose Level 1 (Stratum A)
arm group label: Ixazomib Dose Level 1 (Stratum B)
arm group label: Ixazomib Dose Level 2 (Stratum A)
intervention type: Drug
intervention name: Asparaginase
description: Days 2, 15
Dose ≥ 1 year: 2,500 International units (IU)/m2/dose
≥ 6 months and < 1 year: 2,000 IU/m2/dose
< 6 months: 1,750 IU/m2/dose
Patient with allergic reaction to Pegaspargase can be given Erwinase IM/IV on Mon/Wed/Fri (or every other day per institutional standard) x 6 doses for each dose of Pegaspargase.
Dosing guideline for Erwinase:
1 year: 25,000 IU/m2/dose
6 months and < 1 year: 20,000 IU/m2/dose
< 6 months: 17,500 IU/m2/dose
arm group label: Ixazomib Dose Level -1 (Stratum A)
arm group label: Ixazomib Dose Level 1 (Stratum A)
arm group label: Ixazomib Dose Level 1 (Stratum B)
arm group label: Ixazomib Dose Level 2 (Stratum A)
intervention type: Drug
intervention name: Doxorubicin
description: Day 1
Dose ≥ 1 year: 60mg/m2/dose
≥ 6 months and < 1 year: 48 mg/m2/dose
< 6 months: 42mg/m2/dose
arm group label: Ixazomib Dose Level -1 (Stratum A)
arm group label: Ixazomib Dose Level 1 (Stratum A)
arm group label: Ixazomib Dose Level 1 (Stratum B)
arm group label: Ixazomib Dose Level 2 (Stratum A)
intervention type: Drug
intervention name: Methotrexate (IT)
description: For patients with CNS 1 or CNS 2, on Days 1, 15, and 29
arm group label: Ixazomib Dose Level -1 (Stratum A)
arm group label: Ixazomib Dose Level 1 (Stratum A)
arm group label: Ixazomib Dose Level 1 (Stratum B)
arm group label: Ixazomib Dose Level 2 (Stratum A)
intervention type: Drug
intervention name: Triple IT (Methotrexate, Hydrocortisone, Cytarabine)
description: For patients with CNS 3, on Days 1, 8, 15, 22, and 29
arm group label: Ixazomib Dose Level -1 (Stratum A)
arm group label: Ixazomib Dose Level 1 (Stratum A)
arm group label: Ixazomib Dose Level 1 (Stratum B)
arm group label: Ixazomib Dose Level 2 (Stratum A)
intervention type: Drug
intervention name: Leucovorin
description: For patients with Down syndrome only, on Days 2, 9, 16, 23, and 30 (based on dates when IT Methotrexate or Triple IT is given)
arm group label: Ixazomib Dose Level 1 (Stratum B)
criteria: 
gender: All
minimum age: 1 Year
maximum age: 21 Years
healthy volunteers: No
last name: Terzah Horton, MD
role: Study Chair
affiliation: Baylor College of Medicine
last name: Roy Leong
phone: 323-361-5132
email: rleong@chla.usc.edu
last name: Benjamin Brookhart
phone: 323-361-5429
email: bbrookhart@chla.usc.edu
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
country: Australia
country: United States
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Leukemia
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Leukemia, Lymphoid
mesh term: Lymphoma, Non-Hodgkin
mesh term: Leucovorin
mesh term: Cytarabine
mesh term: Dexamethasone
mesh term: Hydrocortisone
mesh term: Doxorubicin
mesh term: Methotrexate
mesh term: Vincristine
mesh term: Asparaginase
mesh term: Ixazomib
sharing ipd: No