<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/NCT03020030</url>
  </required_header>
  <id_info>
    <org_study_id>16-001</org_study_id>
    <nct_id>NCT03020030</nct_id>
  </id_info>
  <brief_title>Treatment of Newly Diagnosed Acute Lymphoblastic Leukemia in Children and Adolescents</brief_title>
  <official_title>Treatment of Newly Diagnosed Acute Lymphoblastic Leukemia in Children and Adolescents</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dana-Farber Cancer Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Servier</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Dana-Farber Cancer Institute</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>
      Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in children. The&#xD;
      cancer comes from a cell in the blood called a lymphocyte. Normal lymphocytes are produced in&#xD;
      the bone marrow (along with other blood cells) and help fight infections. In ALL, the&#xD;
      cancerous lymphocytes are called lymphoblasts. They do not help fight infection and crowd out&#xD;
      the normal blood cells in the bone marrow so that the body cannot make enough normal blood&#xD;
      cells. ALL is always fatal if it is not treated. With current treatments, most children and&#xD;
      adolescents with this disease will be cured.&#xD;
&#xD;
      The standard treatment for ALL involves about 2 years of chemotherapy. The drugs that are&#xD;
      used, and the doses of the drugs, are similar but not identical for all children and&#xD;
      adolescents with ALL. Some children and adolescents receive stronger treatment, especially&#xD;
      during the first several months. A number of factors are used to decide how strong the&#xD;
      treatment should be to give the best chance for cure. These factors are called &quot;risk&#xD;
      factors&quot;. This trial is studying the use of a new, updated set of risk factors to decide how&#xD;
      strong the treatment will be. The study also will test a new way of dosing a chemotherapy&#xD;
      drug called pegaspargase (which is part of the standard treatment for ALL) based on checking&#xD;
      levels of the drug in the blood and adjusting the dose based on the levels.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      There are a standard set of risk factors which are used to decide how strong treatment should&#xD;
      be for a child with ALL. These risk factors include the child's age when the leukemia is&#xD;
      diagnosed, how high the white blood cell count (WBC) is in the blood, whether or not leukemia&#xD;
      cells are seen in the spinal fluid (referred to as Central Nervous System or CNS status), and&#xD;
      whether or not the leukemia has certain abnormalities in their chromosomes (genetic material&#xD;
      in the cell). Another risk factor is the amount of leukemia in the marrow that can be&#xD;
      measured by a special laboratory test called &quot;MRD&quot; (Minimal Residual Disease) after the first&#xD;
      month of treatment.&#xD;
&#xD;
      Over the last several years, new factors have been identified which help predict how well a&#xD;
      child's leukemia may respond to treatment. These new risk factors include additional&#xD;
      abnormalities in the genes of the leukemia cell, as well the amount of leukemia (MRD level)&#xD;
      at second time point (about 2-3 months after starting treatment).&#xD;
&#xD;
      In this trial, the investigators will use the new risk factors along with old risk factors to&#xD;
      decide how strong the treatment will be. The goal is to better identify those participants&#xD;
      who might benefit from stronger treatment in order to improve their chance for cure. The&#xD;
      investigators also hope to better identify participants who have a high chance of being cured&#xD;
      with standard treatment in order to reduce their chance of side effects while maintaining the&#xD;
      chance of cure.&#xD;
&#xD;
      This trial also aims to study the dosing of a drug called pegaspargase. Pegaspargase is a&#xD;
      chemotherapy drug that is an important part of ALL treatment but it is also can cause many&#xD;
      side effects. With the standard dose of pegaspargase, levels of the drug in the blood are&#xD;
      higher than may be necessary to effectively treat leukemia.&#xD;
&#xD;
      On this research study, the investigators will be comparing the standard dose of pegaspargase&#xD;
      with a new way of dosing the drug based on levels of the drug that we can measure in the&#xD;
      blood. With the new way of doing, treatment will begin with a lower dose. If the levels are&#xD;
      high, the dose will be decreased one more time; however, if at any time the levels are too&#xD;
      low, dosing will be switched back up to the standard dose. The goal of this research study is&#xD;
      to learn whether this new way of dosing (starting at a lower dose and changing the dose based&#xD;
      on drug levels in the blood) will decrease side effects but still be as effective as the&#xD;
      standard dosing of the drug.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">March 3, 2017</start_date>
  <completion_date type="Anticipated">November 2028</completion_date>
  <primary_completion_date type="Anticipated">November 2024</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Complete Remission Rate</measure>
    <time_frame>After 1 month of treatment (Induction IA) for all participants, assessed at the end of first month of treatment in all participants through study completion (expected to take 4-5 years to accrue)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Event-Free Survival</measure>
    <time_frame>From registration to the time of induction failure, relapse, death, or second malignancy, whichever came first, assessed up to 60 months.</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>From registration to the time of death from any cause, assessed up to 60 months.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Free Survival</measure>
    <time_frame>From randomization or direct assignment (for participants who achieved a complete remission and were assigned a final risk group) to the time of relapse, death, or second malignancy, whichever came first, assessed up to 60 months.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Nadir Serum Asparaginase Activity (NSAA)</measure>
    <time_frame>During post-induction therapy with 30-weeks of pegaspargase (15 doses), collected during the first 6 months of therapy for all participants through study completion (expected to take 4-5 years to accrue)</time_frame>
    <description>Proportion of patients receiving pegaspargase with NSAA &gt;= 1.0 IU/mL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Non-allergic Asparaginase Toxicity</measure>
    <time_frame>During post-induction therapy with 30-weeks of pegaspargase (15 doses). collected during the first 6 months of therapy for all participants through study completion (expected to take 4-5 years to accrue)</time_frame>
    <description>Frequency of non-allergic asparaginase-related toxicities, an average of 5 years.</description>
  </secondary_outcome>
  <number_of_arms>10</number_of_arms>
  <enrollment type="Actual">560</enrollment>
  <condition>Acute Lymphoblastic Leukemia, Pediatric</condition>
  <arm_group>
    <arm_group_label>Initial Low Risk (Initial LR)</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Meets all the following criteria: B-ALL, Age 1-&lt;15 years, WBC &lt; 50,000/microliter, CNS-1 or CNS-2, no BCR-ABL1, no iAMP21, and no VHR characteristics.&#xD;
Treated with Induction IA (vincristine, dexamethasone, pegaspargase), Induction IB (cyclophosphamide, cytarabine, mercaptopurine), Consolidation IA (vincristine, high-dose methotrexate + leucovorin, mercaptopurine). IT chemotherapy in all phases. Final risk group assigned by end of Consolidation IA.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Initial High Risk (Initial HR)</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Meets at least one of the following criteria: Age &gt;=15 years, WBC &gt;=50,000/microliter, CNS-3, T-ALL, iAMP21, BCR-ABL1&#xD;
And: No VHR characteristics&#xD;
Treated with Induction IA (vincristine, dexamethasone, pegaspargase, doxorubicin + dexrazoxane), Induction IB (cyclophosphamide, cytarabine, mercaptopurine), Consolidation IA (vincristine, high-dose methotrexate + leucovorin, mercaptopurine). IT chemotherapy in all phases. Final risk group assigned by end of Consolidation IA.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Initial Very High Risk (Initial VHR)</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Any of the following are present: IKZF1 deletion, MLL (KMT2A) rearrangement, low hypodiploidy, t(17;19)&#xD;
Treated with Induction IA (vincristine, dexamethasone, pegaspargase, doxorubicin + dexrazoxane), Induction IB (cyclophosphamide, cytarabine, mercaptopurine), Consolidation IA (vincristine, high-dose methotrexate + leucovorin, mercaptopurine). IT chemotherapy in all phases. Final risk group assigned by end of Consolidation IA.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Final Low Risk (Final LR)</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Initial Low Risk and Low MRD (&lt;0.0001) at first time point (Day 32)&#xD;
Final Risk Group assigned at end of Consolidation IA. Subsequent therapy as follows:&#xD;
CNS phase (vincristine, dexamethasone, mercaptopurine, pegaspargase [by randomization or direct assignment], IT chemotherapy); Consolidation II (vincristine, dexamethasone, mercaptopurine, methotrexate, pegaspargase [by randomization or direct assignment], IT chemotherapy); Continuation (vincristine, dexamethasone, mercaptopurine, methotrexate, IT chemotherapy).&#xD;
All treatment completed 24 months from date of complete remission.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Final Intermediate Risk (Final IR)</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Initial High Risk and Low MRD (&lt;0.0001) at first time point (Day 32)&#xD;
Final Risk Group assigned at end of Consolidation IA. Subsequent therapy as follows:&#xD;
CNS phase (vincristine, dexamethasone, mercaptopurine, pegaspargase [by randomization or direct assignment], IT chemotherapy); Consolidation II (vincristine, dexamethasone, mercaptopurine, doxorubicin + dexrazoxane, pegaspargase [by randomization or direct assignment], IT chemotherapy); Continuation (vincristine, dexamethasone, mercaptopurine, methotrexate, IT chemotherapy).&#xD;
All treatment completed 24 months from date of complete remission.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Final High Risk (Final HR)</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Initial Low Risk or Initial High Risk with High MRD (&gt;=0.0001) at first time point (Day 32) but low MRD (&lt;0.001) at second time point (week 10-12)&#xD;
Final Risk Group assigned at end of Consolidation IA. Subsequent therapy as follows:&#xD;
CNS phase (vincristine, dexamethasone, mercaptopurine, pegaspargase [by randomization or direct assignment], IT chemotherapy); Consolidation II (vincristine, dexamethasone, mercaptopurine, doxorubicin + dexrazoxane, pegaspargase [by randomization or direct assignment], IT chemotherapy); Continuation (vincristine, dexamethasone, mercaptopurine, methotrexate, IT chemotherapy).&#xD;
All treatment completed 24 months from date of complete remission.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Final Very High Risk (Final VHR)</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Initial VHR or any patient with high MRD (&gt;=0.001) at second time point (week 10-12)&#xD;
Final Risk Group assigned at end of Consolidation IA. Subsequent therapy as follows:&#xD;
Consolidation IB/B-ALL (High-dose methotrexate + leucovorin, cyclophosphamide, etoposide, IT chemotherapy); Consolidation IB/T-ALL (nelararbine, cyclophosphamide, etoposide); Consolidation IC (High-dose cytarabine, etoposide, dexamethasone, pegaspargase [by direct assignment], IT chemotherapy); CNS phase (vincristine, dexamethasone, mercaptopurine, pegaspargase [by direct assignment], IT chemotherapy); Consolidation II (vincristine, dexamethasone, mercaptopurine, doxorubicin + dexrazoxane, pegaspargase [by direct assignment], IT chemotherapy); Continuation (vincristine, dexamethasone, mercaptopurine, methotrexate, IT chemotherapy).&#xD;
Dasatinib administered daily during all phases to pts with ABL1-class fusions. All treatment completed 24 months from date of complete remission.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Fixed Dose Pegaspargase</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Final LR, IR, HR patients who consent to randomization and are assigned to receive 15 doses of pegaspargase every 2-weeks at standard fixed-dose (2500 IU/m2/dose).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Reduced Dose (PK-Adjusted) Pegaspargase</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Final LR, IR, HR patients who consent to randomization and are assigned to receive 15 doses of pegaspargase every 2-weeks beginning at a reduced dose (2000 IU/m2/dose); subsequent doses adjusted based on nadir serum asparaginase activity (NSAA) levels, with goal of maintaining NSAA between 0.4 and 1.0 IU/mL. Closed to Enrollment.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Direct Assignment</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>All VHR patients, and any Final LR, IR, HR patients who decline randomization: Assigned to receive standard dosing of pegaspargase (15 doses of pegaspargase every 2-weeks at standard fixed-dose; 2500 IU/m2/dose).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pegaspargase</intervention_name>
    <description>Arm A: Standard/Fixed Dose Pegaspargase (2500 IU/m2 every 2 weeks) Arm B: Reduced Dose (PK-adjusted) Pegaspargase (Starting Dose: 2000 IU/m2) Arm X: Directly Assigned Standard Dose (2500 IU/m2): For all VHR and patients who decline randomization</description>
    <arm_group_label>Direct Assignment</arm_group_label>
    <arm_group_label>Final High Risk (Final HR)</arm_group_label>
    <arm_group_label>Final Intermediate Risk (Final IR)</arm_group_label>
    <arm_group_label>Final Low Risk (Final LR)</arm_group_label>
    <arm_group_label>Final Very High Risk (Final VHR)</arm_group_label>
    <arm_group_label>Fixed Dose Pegaspargase</arm_group_label>
    <arm_group_label>Initial High Risk (Initial HR)</arm_group_label>
    <arm_group_label>Initial Low Risk (Initial LR)</arm_group_label>
    <arm_group_label>Initial Very High Risk (Initial VHR)</arm_group_label>
    <arm_group_label>Reduced Dose (PK-Adjusted) Pegaspargase</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Erwinia asparaginase</intervention_name>
    <description>Only for patients with Pegaspargase allergy or silent inactivation.</description>
    <arm_group_label>Direct Assignment</arm_group_label>
    <arm_group_label>Final High Risk (Final HR)</arm_group_label>
    <arm_group_label>Final Intermediate Risk (Final IR)</arm_group_label>
    <arm_group_label>Final Low Risk (Final LR)</arm_group_label>
    <arm_group_label>Final Very High Risk (Final VHR)</arm_group_label>
    <arm_group_label>Fixed Dose Pegaspargase</arm_group_label>
    <arm_group_label>Initial High Risk (Initial HR)</arm_group_label>
    <arm_group_label>Initial Low Risk (Initial LR)</arm_group_label>
    <arm_group_label>Initial Very High Risk (Initial VHR)</arm_group_label>
    <arm_group_label>Reduced Dose (PK-Adjusted) Pegaspargase</arm_group_label>
    <other_name>ERWINAZE®</other_name>
    <other_name>ERWINIA CHRYSANTHEMI</other_name>
    <other_name>ERWINASE®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>Standard of Care</description>
    <arm_group_label>Final Very High Risk (Final VHR)</arm_group_label>
    <arm_group_label>Initial High Risk (Initial HR)</arm_group_label>
    <arm_group_label>Initial Low Risk (Initial LR)</arm_group_label>
    <arm_group_label>Initial Very High Risk (Initial VHR)</arm_group_label>
    <other_name>CYTOXAN</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CYTARABINE</intervention_name>
    <description>Standard of Care</description>
    <arm_group_label>Final High Risk (Final HR)</arm_group_label>
    <arm_group_label>Final Intermediate Risk (Final IR)</arm_group_label>
    <arm_group_label>Final Low Risk (Final LR)</arm_group_label>
    <arm_group_label>Final Very High Risk (Final VHR)</arm_group_label>
    <arm_group_label>Initial High Risk (Initial HR)</arm_group_label>
    <arm_group_label>Initial Low Risk (Initial LR)</arm_group_label>
    <arm_group_label>Initial Very High Risk (Initial VHR)</arm_group_label>
    <other_name>CYTOSINE ARABINOSIDE</other_name>
    <other_name>ARA-C</other_name>
    <other_name>CYTOSAR®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>DASATINIB</intervention_name>
    <description>Standard of Care</description>
    <arm_group_label>Final Very High Risk (Final VHR)</arm_group_label>
    <arm_group_label>Initial Very High Risk (Initial VHR)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>DEXAMETHASONE</intervention_name>
    <description>Standard of Care</description>
    <arm_group_label>Final High Risk (Final HR)</arm_group_label>
    <arm_group_label>Final Intermediate Risk (Final IR)</arm_group_label>
    <arm_group_label>Final Low Risk (Final LR)</arm_group_label>
    <arm_group_label>Final Very High Risk (Final VHR)</arm_group_label>
    <arm_group_label>Initial High Risk (Initial HR)</arm_group_label>
    <arm_group_label>Initial Low Risk (Initial LR)</arm_group_label>
    <arm_group_label>Initial Very High Risk (Initial VHR)</arm_group_label>
    <other_name>DECADRON®</other_name>
    <other_name>HEXADROL®,</other_name>
    <other_name>DEXONE®,</other_name>
    <other_name>DEXAMETH®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexrazoxane</intervention_name>
    <description>Standard of Care</description>
    <arm_group_label>Final High Risk (Final HR)</arm_group_label>
    <arm_group_label>Final Intermediate Risk (Final IR)</arm_group_label>
    <arm_group_label>Final Very High Risk (Final VHR)</arm_group_label>
    <arm_group_label>Initial High Risk (Initial HR)</arm_group_label>
    <arm_group_label>Initial Very High Risk (Initial VHR)</arm_group_label>
    <other_name>Zinecard</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Doxorubicin</intervention_name>
    <description>Standard of Care</description>
    <arm_group_label>Final High Risk (Final HR)</arm_group_label>
    <arm_group_label>Final Intermediate Risk (Final IR)</arm_group_label>
    <arm_group_label>Final Very High Risk (Final VHR)</arm_group_label>
    <arm_group_label>Initial High Risk (Initial HR)</arm_group_label>
    <arm_group_label>Initial Very High Risk (Initial VHR)</arm_group_label>
    <other_name>ADRIAMYCIN®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ETOPOSIDE</intervention_name>
    <description>Standard of Care</description>
    <arm_group_label>Final Very High Risk (Final VHR)</arm_group_label>
    <arm_group_label>Initial Very High Risk (Initial VHR)</arm_group_label>
    <other_name>VePesid</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>HYDROCORTISONE</intervention_name>
    <description>Standard of Care</description>
    <arm_group_label>Final High Risk (Final HR)</arm_group_label>
    <arm_group_label>Final Intermediate Risk (Final IR)</arm_group_label>
    <arm_group_label>Final Low Risk (Final LR)</arm_group_label>
    <arm_group_label>Final Very High Risk (Final VHR)</arm_group_label>
    <arm_group_label>Initial High Risk (Initial HR)</arm_group_label>
    <arm_group_label>Initial Low Risk (Initial LR)</arm_group_label>
    <arm_group_label>Initial Very High Risk (Initial VHR)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>LEUCOVORIN CALCIUM</intervention_name>
    <description>Standard of Care</description>
    <arm_group_label>Final Very High Risk (Final VHR)</arm_group_label>
    <arm_group_label>Initial High Risk (Initial HR)</arm_group_label>
    <arm_group_label>Initial Low Risk (Initial LR)</arm_group_label>
    <arm_group_label>Initial Very High Risk (Initial VHR)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MERCAPTOPURINE</intervention_name>
    <description>Standard of Care</description>
    <arm_group_label>Final High Risk (Final HR)</arm_group_label>
    <arm_group_label>Final Intermediate Risk (Final IR)</arm_group_label>
    <arm_group_label>Final Low Risk (Final LR)</arm_group_label>
    <arm_group_label>Final Very High Risk (Final VHR)</arm_group_label>
    <arm_group_label>Initial High Risk (Initial HR)</arm_group_label>
    <arm_group_label>Initial Low Risk (Initial LR)</arm_group_label>
    <arm_group_label>Initial Very High Risk (Initial VHR)</arm_group_label>
    <other_name>6-MP</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>METHOTREXATE</intervention_name>
    <description>Standard of Care</description>
    <arm_group_label>Final High Risk (Final HR)</arm_group_label>
    <arm_group_label>Final Intermediate Risk (Final IR)</arm_group_label>
    <arm_group_label>Final Low Risk (Final LR)</arm_group_label>
    <arm_group_label>Final Very High Risk (Final VHR)</arm_group_label>
    <arm_group_label>Initial High Risk (Initial HR)</arm_group_label>
    <arm_group_label>Initial Low Risk (Initial LR)</arm_group_label>
    <arm_group_label>Initial Very High Risk (Initial VHR)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NELARABINE</intervention_name>
    <description>Standard of Care</description>
    <arm_group_label>Final Very High Risk (Final VHR)</arm_group_label>
    <arm_group_label>Initial Very High Risk (Initial VHR)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vincristine</intervention_name>
    <description>Standard of Care</description>
    <arm_group_label>Final High Risk (Final HR)</arm_group_label>
    <arm_group_label>Final Intermediate Risk (Final IR)</arm_group_label>
    <arm_group_label>Final Low Risk (Final LR)</arm_group_label>
    <arm_group_label>Final Very High Risk (Final VHR)</arm_group_label>
    <arm_group_label>Initial High Risk (Initial HR)</arm_group_label>
    <arm_group_label>Initial Low Risk (Initial LR)</arm_group_label>
    <arm_group_label>Initial Very High Risk (Initial VHR)</arm_group_label>
    <other_name>Oncovin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Confirmed diagnosis of acute lymphoblastic leukemia. Diagnosis should be made by bone&#xD;
             marrow aspirate or biopsy demonstrating ≥ 25% involvement by lymphoblasts, with flow&#xD;
             cytometry or immunohistochemistry confirming B-precursor or T-ALL phenotype.&#xD;
&#xD;
             -- For patients with circulating blasts in the peripheral blood, flow cytometry&#xD;
             confirmation of B-ALL or T-ALL phenotype is sufficient for registration onto the&#xD;
             study. Bone marrow aspirate and/or biopsy should be performed as soon as feasible,&#xD;
             preferably prior to the initiation of any therapy.&#xD;
&#xD;
          2. Prior Therapy: No prior therapy is allowed except for the following:&#xD;
&#xD;
               -  Corticosteroids: Short courses of corticosteroid (defined as ≤ 7 days of&#xD;
                  corticosteroids within the 4-weeks preceding registration) are allowed prior to&#xD;
                  registration.&#xD;
&#xD;
                  --- Participants who have been on corticosteroids chronically (defined as more&#xD;
                  than 7 days of corticosteroids within the 4-weeks preceding registration or more&#xD;
                  than 28 days of corticosteroids over the preceding 6 months) are not eligible.&#xD;
&#xD;
               -  IT cytarabine: A single dose of intrathecal cytarabine (at the time of the&#xD;
                  diagnostic lumbar puncture) is allowed prior to registration. If patient has&#xD;
                  received IT cytarabine prior to registration, Day 1 IT cytarabine should not be&#xD;
                  administered.&#xD;
&#xD;
               -  Emergent Radiation Therapy: Emergent radiation to the mediastinum or other&#xD;
                  life-threatening masses is allowed prior to registration.&#xD;
&#xD;
          3. Age: 365 days to &lt; 22 years&#xD;
&#xD;
          4. Direct bilirubin &lt; 1.4 mg/dL (23.9 micromoles/L).&#xD;
&#xD;
          5. Ability of parent or guardian to understand and the willingness to sign a written&#xD;
             informed consent document.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Mature B-cell (Burkitt's) ALL (defined by the presence of surface immunoglobulin&#xD;
             and/or the t(8;14)(q24;q32), t(8;22), or t(2;8) translocation and/or c-myc-gene&#xD;
             rearrangement).&#xD;
&#xD;
          2. World Health Organization diagnostic criteria of mixed phenotype acute leukemia (MPAL)&#xD;
             or leukemia of ambiguous lineage&#xD;
&#xD;
          3. Any chemotherapy or radiotherapy for previous malignancy are not eligible.&#xD;
&#xD;
          4. Treatment in past with any anti-neoplastic agent, including methotrexate,&#xD;
             6-mercaptopurine, 6-thioguanine, vincristine cyclophosphamide, cytarabine (except for&#xD;
             IT cytarabine), or any anthracycline, for any reason (eg, rheumatologic or autoimmune&#xD;
             condition).&#xD;
&#xD;
          5. Currently receiving any investigational agents.&#xD;
&#xD;
          6. Known HIV-positivity&#xD;
&#xD;
          7. Uncontrolled intercurrent illness including, but not limited to ongoing infection with&#xD;
             vital sign instability (hypotension, respiratory insufficiency), life-threatening&#xD;
             acute tumor lysis syndrome (eg, with renal failure), symptomatic congestive heart&#xD;
             failure, cardiac arrhythmia, intracranial or other uncontrolled bleeding, or&#xD;
             psychiatric illness/social situations that would limit compliance with study&#xD;
             requirements.&#xD;
&#xD;
          8. Pregnant women are excluded from this study because many of the agents used on this&#xD;
             protocol have potential for teratogenic and/or abortifacient effects. Because there is&#xD;
             an unknown but potential risk of adverse events in nursing infants secondary to&#xD;
             treatment of the mother with these chemotherapy agents, breastfeeding should be&#xD;
             discontinued if the mother is enrolled.&#xD;
&#xD;
          9. History of a previous malignancy. Exception: Individuals with a previous malignancy&#xD;
             treated with surgery only (no chemotherapy or radiotherapy) more than 5 years prior to&#xD;
             registration may be enrolled.&#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>Lewis Silveman, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Dana-Farber Cancer Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Boston Children's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </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>
  </location>
  <location>
    <facility>
      <name>Rutgers Cancer Institute of New Jersey</name>
      <address>
        <city>New Brunswick</city>
        <state>New Jersey</state>
        <zip>08903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Montefiore Medical Center</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10467</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Roswell Park Cancer Institute</name>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <zip>14263</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbia University Medical Center, Morgan Stanley Children's Hospital of New York-Presbyterian</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hasbro Children's Hospital / Rhode Island Hospital</name>
      <address>
        <city>Providence</city>
        <state>Rhode Island</state>
        <zip>02903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Sainte Justine, University of Montreal</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier U. de Quebec</name>
      <address>
        <city>Quebec City</city>
        <state>Quebec</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>January 6, 2017</study_first_submitted>
  <study_first_submitted_qc>January 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 13, 2017</study_first_posted>
  <last_update_submitted>May 1, 2023</last_update_submitted>
  <last_update_submitted_qc>May 1, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Dana-Farber Cancer Institute</investigator_affiliation>
    <investigator_full_name>Lewis B. Silverman, MD</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>acute lymphoblastic leukemia</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>
  </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>Cyclophosphamide</mesh_term>
    <mesh_term>Doxorubicin</mesh_term>
    <mesh_term>Methotrexate</mesh_term>
    <mesh_term>Etoposide</mesh_term>
    <mesh_term>Vincristine</mesh_term>
    <mesh_term>Asparaginase</mesh_term>
    <mesh_term>Dasatinib</mesh_term>
    <mesh_term>Mercaptopurine</mesh_term>
    <mesh_term>Pegaspargase</mesh_term>
    <mesh_term>Dexrazoxane</mesh_term>
    <mesh_term>Razoxane</mesh_term>
    <mesh_term>Levoleucovorin</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/NCT03020030
org study id: 16-001
nct id: NCT03020030
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in children. The
      cancer comes from a cell in the blood called a lymphocyte. Normal lymphocytes are produced in
      the bone marrow (along with other blood cells) and help fight infections. In ALL, the
      cancerous lymphocytes are called lymphoblasts. They do not help fight infection and crowd out
      the normal blood cells in the bone marrow so that the body cannot make enough normal blood
      cells. ALL is always fatal if it is not treated. With current treatments, most children and
      adolescents with this disease will be cured.

      The standard treatment for ALL involves about 2 years of chemotherapy. The drugs that are
      used, and the doses of the drugs, are similar but not identical for all children and
      adolescents with ALL. Some children and adolescents receive stronger treatment, especially
      during the first several months. A number of factors are used to decide how strong the
      treatment should be to give the best chance for cure. These factors are called "risk
      factors". This trial is studying the use of a new, updated set of risk factors to decide how
      strong the treatment will be. The study also will test a new way of dosing a chemotherapy
      drug called pegaspargase (which is part of the standard treatment for ALL) based on checking
      levels of the drug in the blood and adjusting the dose based on the levels.
There are a standard set of risk factors which are used to decide how strong treatment should
      be for a child with ALL. These risk factors include the child's age when the leukemia is
      diagnosed, how high the white blood cell count (WBC) is in the blood, whether or not leukemia
      cells are seen in the spinal fluid (referred to as Central Nervous System or CNS status), and
      whether or not the leukemia has certain abnormalities in their chromosomes (genetic material
      in the cell). Another risk factor is the amount of leukemia in the marrow that can be
      measured by a special laboratory test called "MRD" (Minimal Residual Disease) after the first
      month of treatment.

      Over the last several years, new factors have been identified which help predict how well a
      child's leukemia may respond to treatment. These new risk factors include additional
      abnormalities in the genes of the leukemia cell, as well the amount of leukemia (MRD level)
      at second time point (about 2-3 months after starting treatment).

      In this trial, the investigators will use the new risk factors along with old risk factors to
      decide how strong the treatment will be. The goal is to better identify those participants
      who might benefit from stronger treatment in order to improve their chance for cure. The
      investigators also hope to better identify participants who have a high chance of being cured
      with standard treatment in order to reduce their chance of side effects while maintaining the
      chance of cure.

      This trial also aims to study the dosing of a drug called pegaspargase. Pegaspargase is a
      chemotherapy drug that is an important part of ALL treatment but it is also can cause many
      side effects. With the standard dose of pegaspargase, levels of the drug in the blood are
      higher than may be necessary to effectively treat leukemia.

      On this research study, the investigators will be comparing the standard dose of pegaspargase
      with a new way of dosing the drug based on levels of the drug that we can measure in the
      blood. With the new way of doing, treatment will begin with a lower dose. If the levels are
      high, the dose will be decreased one more time; however, if at any time the levels are too
      low, dosing will be switched back up to the standard dose. The goal of this research study is
      to learn whether this new way of dosing (starting at a lower dose and changing the dose based
      on drug levels in the blood) will decrease side effects but still be as effective as the
      standard dosing of the drug.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Complete Remission Rate
time frame: After 1 month of treatment (Induction IA) for all participants, assessed at the end of first month of treatment in all participants through study completion (expected to take 4-5 years to accrue)
measure: Event-Free Survival
time frame: From registration to the time of induction failure, relapse, death, or second malignancy, whichever came first, assessed up to 60 months.
measure: Overall Survival
time frame: From registration to the time of death from any cause, assessed up to 60 months.
measure: Disease Free Survival
time frame: From randomization or direct assignment (for participants who achieved a complete remission and were assigned a final risk group) to the time of relapse, death, or second malignancy, whichever came first, assessed up to 60 months.
measure: Nadir Serum Asparaginase Activity (NSAA)
time frame: During post-induction therapy with 30-weeks of pegaspargase (15 doses), collected during the first 6 months of therapy for all participants through study completion (expected to take 4-5 years to accrue)
description: Proportion of patients receiving pegaspargase with NSAA >= 1.0 IU/mL
measure: Non-allergic Asparaginase Toxicity
time frame: During post-induction therapy with 30-weeks of pegaspargase (15 doses). collected during the first 6 months of therapy for all participants through study completion (expected to take 4-5 years to accrue)
description: Frequency of non-allergic asparaginase-related toxicities, an average of 5 years.
arm group label: Initial Low Risk (Initial LR)
arm group type: Other
description: Meets all the following criteria: B-ALL, Age 1-<15 years, WBC < 50,000/microliter, CNS-1 or CNS-2, no BCR-ABL1, no iAMP21, and no VHR characteristics.
Treated with Induction IA (vincristine, dexamethasone, pegaspargase), Induction IB (cyclophosphamide, cytarabine, mercaptopurine), Consolidation IA (vincristine, high-dose methotrexate + leucovorin, mercaptopurine). IT chemotherapy in all phases. Final risk group assigned by end of Consolidation IA.
arm group label: Initial High Risk (Initial HR)
arm group type: Other
description: Meets at least one of the following criteria: Age >=15 years, WBC >=50,000/microliter, CNS-3, T-ALL, iAMP21, BCR-ABL1
And: No VHR characteristics
Treated with Induction IA (vincristine, dexamethasone, pegaspargase, doxorubicin + dexrazoxane), Induction IB (cyclophosphamide, cytarabine, mercaptopurine), Consolidation IA (vincristine, high-dose methotrexate + leucovorin, mercaptopurine). IT chemotherapy in all phases. Final risk group assigned by end of Consolidation IA.
arm group label: Initial Very High Risk (Initial VHR)
arm group type: Other
description: Any of the following are present: IKZF1 deletion, MLL (KMT2A) rearrangement, low hypodiploidy, t(17;19)
Treated with Induction IA (vincristine, dexamethasone, pegaspargase, doxorubicin + dexrazoxane), Induction IB (cyclophosphamide, cytarabine, mercaptopurine), Consolidation IA (vincristine, high-dose methotrexate + leucovorin, mercaptopurine). IT chemotherapy in all phases. Final risk group assigned by end of Consolidation IA.
arm group label: Final Low Risk (Final LR)
arm group type: Other
description: Initial Low Risk and Low MRD (<0.0001) at first time point (Day 32)
Final Risk Group assigned at end of Consolidation IA. Subsequent therapy as follows:
CNS phase (vincristine, dexamethasone, mercaptopurine, pegaspargase [by randomization or direct assignment], IT chemotherapy); Consolidation II (vincristine, dexamethasone, mercaptopurine, methotrexate, pegaspargase [by randomization or direct assignment], IT chemotherapy); Continuation (vincristine, dexamethasone, mercaptopurine, methotrexate, IT chemotherapy).
All treatment completed 24 months from date of complete remission.
arm group label: Final Intermediate Risk (Final IR)
arm group type: Other
description: Initial High Risk and Low MRD (<0.0001) at first time point (Day 32)
Final Risk Group assigned at end of Consolidation IA. Subsequent therapy as follows:
CNS phase (vincristine, dexamethasone, mercaptopurine, pegaspargase [by randomization or direct assignment], IT chemotherapy); Consolidation II (vincristine, dexamethasone, mercaptopurine, doxorubicin + dexrazoxane, pegaspargase [by randomization or direct assignment], IT chemotherapy); Continuation (vincristine, dexamethasone, mercaptopurine, methotrexate, IT chemotherapy).
All treatment completed 24 months from date of complete remission.
arm group label: Final High Risk (Final HR)
arm group type: Other
description: Initial Low Risk or Initial High Risk with High MRD (>=0.0001) at first time point (Day 32) but low MRD (<0.001) at second time point (week 10-12)
Final Risk Group assigned at end of Consolidation IA. Subsequent therapy as follows:
CNS phase (vincristine, dexamethasone, mercaptopurine, pegaspargase [by randomization or direct assignment], IT chemotherapy); Consolidation II (vincristine, dexamethasone, mercaptopurine, doxorubicin + dexrazoxane, pegaspargase [by randomization or direct assignment], IT chemotherapy); Continuation (vincristine, dexamethasone, mercaptopurine, methotrexate, IT chemotherapy).
All treatment completed 24 months from date of complete remission.
arm group label: Final Very High Risk (Final VHR)
arm group type: Other
description: Initial VHR or any patient with high MRD (>=0.001) at second time point (week 10-12)
Final Risk Group assigned at end of Consolidation IA. Subsequent therapy as follows:
Consolidation IB/B-ALL (High-dose methotrexate + leucovorin, cyclophosphamide, etoposide, IT chemotherapy); Consolidation IB/T-ALL (nelararbine, cyclophosphamide, etoposide); Consolidation IC (High-dose cytarabine, etoposide, dexamethasone, pegaspargase [by direct assignment], IT chemotherapy); CNS phase (vincristine, dexamethasone, mercaptopurine, pegaspargase [by direct assignment], IT chemotherapy); Consolidation II (vincristine, dexamethasone, mercaptopurine, doxorubicin + dexrazoxane, pegaspargase [by direct assignment], IT chemotherapy); Continuation (vincristine, dexamethasone, mercaptopurine, methotrexate, IT chemotherapy).
Dasatinib administered daily during all phases to pts with ABL1-class fusions. All treatment completed 24 months from date of complete remission.
arm group label: Fixed Dose Pegaspargase
arm group type: Active Comparator
description: Final LR, IR, HR patients who consent to randomization and are assigned to receive 15 doses of pegaspargase every 2-weeks at standard fixed-dose (2500 IU/m2/dose).
arm group label: Reduced Dose (PK-Adjusted) Pegaspargase
arm group type: Experimental
description: Final LR, IR, HR patients who consent to randomization and are assigned to receive 15 doses of pegaspargase every 2-weeks beginning at a reduced dose (2000 IU/m2/dose); subsequent doses adjusted based on nadir serum asparaginase activity (NSAA) levels, with goal of maintaining NSAA between 0.4 and 1.0 IU/mL. Closed to Enrollment.
arm group label: Direct Assignment
arm group type: Other
description: All VHR patients, and any Final LR, IR, HR patients who decline randomization: Assigned to receive standard dosing of pegaspargase (15 doses of pegaspargase every 2-weeks at standard fixed-dose; 2500 IU/m2/dose).
intervention type: Drug
intervention name: Pegaspargase
description: Arm A: Standard/Fixed Dose Pegaspargase (2500 IU/m2 every 2 weeks) Arm B: Reduced Dose (PK-adjusted) Pegaspargase (Starting Dose: 2000 IU/m2) Arm X: Directly Assigned Standard Dose (2500 IU/m2): For all VHR and patients who decline randomization
arm group label: Direct Assignment
arm group label: Final High Risk (Final HR)
arm group label: Final Intermediate Risk (Final IR)
arm group label: Final Low Risk (Final LR)
arm group label: Final Very High Risk (Final VHR)
arm group label: Fixed Dose Pegaspargase
arm group label: Initial High Risk (Initial HR)
arm group label: Initial Low Risk (Initial LR)
arm group label: Initial Very High Risk (Initial VHR)
arm group label: Reduced Dose (PK-Adjusted) Pegaspargase
intervention type: Drug
intervention name: Erwinia asparaginase
description: Only for patients with Pegaspargase allergy or silent inactivation.
arm group label: Direct Assignment
arm group label: Final High Risk (Final HR)
arm group label: Final Intermediate Risk (Final IR)
arm group label: Final Low Risk (Final LR)
arm group label: Final Very High Risk (Final VHR)
arm group label: Fixed Dose Pegaspargase
arm group label: Initial High Risk (Initial HR)
arm group label: Initial Low Risk (Initial LR)
arm group label: Initial Very High Risk (Initial VHR)
arm group label: Reduced Dose (PK-Adjusted) Pegaspargase
other name: ERWINAZE®
other name: ERWINIA CHRYSANTHEMI
other name: ERWINASE®
intervention type: Drug
intervention name: Cyclophosphamide
description: Standard of Care
arm group label: Final Very High Risk (Final VHR)
arm group label: Initial High Risk (Initial HR)
arm group label: Initial Low Risk (Initial LR)
arm group label: Initial Very High Risk (Initial VHR)
other name: CYTOXAN
intervention type: Drug
intervention name: CYTARABINE
description: Standard of Care
arm group label: Final High Risk (Final HR)
arm group label: Final Intermediate Risk (Final IR)
arm group label: Final Low Risk (Final LR)
arm group label: Final Very High Risk (Final VHR)
arm group label: Initial High Risk (Initial HR)
arm group label: Initial Low Risk (Initial LR)
arm group label: Initial Very High Risk (Initial VHR)
other name: CYTOSINE ARABINOSIDE
other name: ARA-C
other name: CYTOSAR®
intervention type: Drug
intervention name: DASATINIB
description: Standard of Care
arm group label: Final Very High Risk (Final VHR)
arm group label: Initial Very High Risk (Initial VHR)
intervention type: Drug
intervention name: DEXAMETHASONE
description: Standard of Care
arm group label: Final High Risk (Final HR)
arm group label: Final Intermediate Risk (Final IR)
arm group label: Final Low Risk (Final LR)
arm group label: Final Very High Risk (Final VHR)
arm group label: Initial High Risk (Initial HR)
arm group label: Initial Low Risk (Initial LR)
arm group label: Initial Very High Risk (Initial VHR)
other name: DECADRON®
other name: HEXADROL®,
other name: DEXONE®,
other name: DEXAMETH®
intervention type: Drug
intervention name: Dexrazoxane
description: Standard of Care
arm group label: Final High Risk (Final HR)
arm group label: Final Intermediate Risk (Final IR)
arm group label: Final Very High Risk (Final VHR)
arm group label: Initial High Risk (Initial HR)
arm group label: Initial Very High Risk (Initial VHR)
other name: Zinecard
intervention type: Drug
intervention name: Doxorubicin
description: Standard of Care
arm group label: Final High Risk (Final HR)
arm group label: Final Intermediate Risk (Final IR)
arm group label: Final Very High Risk (Final VHR)
arm group label: Initial High Risk (Initial HR)
arm group label: Initial Very High Risk (Initial VHR)
other name: ADRIAMYCIN®
intervention type: Drug
intervention name: ETOPOSIDE
description: Standard of Care
arm group label: Final Very High Risk (Final VHR)
arm group label: Initial Very High Risk (Initial VHR)
other name: VePesid
intervention type: Drug
intervention name: HYDROCORTISONE
description: Standard of Care
arm group label: Final High Risk (Final HR)
arm group label: Final Intermediate Risk (Final IR)
arm group label: Final Low Risk (Final LR)
arm group label: Final Very High Risk (Final VHR)
arm group label: Initial High Risk (Initial HR)
arm group label: Initial Low Risk (Initial LR)
arm group label: Initial Very High Risk (Initial VHR)
intervention type: Drug
intervention name: LEUCOVORIN CALCIUM
description: Standard of Care
arm group label: Final Very High Risk (Final VHR)
arm group label: Initial High Risk (Initial HR)
arm group label: Initial Low Risk (Initial LR)
arm group label: Initial Very High Risk (Initial VHR)
intervention type: Drug
intervention name: MERCAPTOPURINE
description: Standard of Care
arm group label: Final High Risk (Final HR)
arm group label: Final Intermediate Risk (Final IR)
arm group label: Final Low Risk (Final LR)
arm group label: Final Very High Risk (Final VHR)
arm group label: Initial High Risk (Initial HR)
arm group label: Initial Low Risk (Initial LR)
arm group label: Initial Very High Risk (Initial VHR)
other name: 6-MP
intervention type: Drug
intervention name: METHOTREXATE
description: Standard of Care
arm group label: Final High Risk (Final HR)
arm group label: Final Intermediate Risk (Final IR)
arm group label: Final Low Risk (Final LR)
arm group label: Final Very High Risk (Final VHR)
arm group label: Initial High Risk (Initial HR)
arm group label: Initial Low Risk (Initial LR)
arm group label: Initial Very High Risk (Initial VHR)
intervention type: Drug
intervention name: NELARABINE
description: Standard of Care
arm group label: Final Very High Risk (Final VHR)
arm group label: Initial Very High Risk (Initial VHR)
intervention type: Drug
intervention name: Vincristine
description: Standard of Care
arm group label: Final High Risk (Final HR)
arm group label: Final Intermediate Risk (Final IR)
arm group label: Final Low Risk (Final LR)
arm group label: Final Very High Risk (Final VHR)
arm group label: Initial High Risk (Initial HR)
arm group label: Initial Low Risk (Initial LR)
arm group label: Initial Very High Risk (Initial VHR)
other name: Oncovin
criteria: 
gender: All
minimum age: 1 Year
maximum age: 21 Years
healthy volunteers: No
last name: Lewis Silveman, MD
role: Principal Investigator
affiliation: Dana-Farber Cancer Institute
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Canada
country: United States
responsible party type: Principal Investigator
investigator affiliation: Dana-Farber Cancer Institute
investigator full name: Lewis B. Silverman, MD
investigator title: Principal Investigator
mesh term: Leukemia
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Leukemia, Lymphoid
mesh term: Leucovorin
mesh term: Cytarabine
mesh term: Dexamethasone
mesh term: Hydrocortisone
mesh term: Cyclophosphamide
mesh term: Doxorubicin
mesh term: Methotrexate
mesh term: Etoposide
mesh term: Vincristine
mesh term: Asparaginase
mesh term: Dasatinib
mesh term: Mercaptopurine
mesh term: Pegaspargase
mesh term: Dexrazoxane
mesh term: Razoxane
mesh term: Levoleucovorin
sharing ipd: No