Treatment of Acute Lymphoblastic Leukemia in Children
Condition: Acute Lymphoblastic Leukemia
MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
Study type: Interventional
Phase: Phase 3

Summary: 
      The purpose of this study is to reduce the side-effects from anti-leukemia therapy. The
      therapy in this study is based upon treatment information learned from prior clinical
      research programs as well as from laboratory research.
    

Detailed description: 
      -  Children with acute lymphoblastic leukemia are treated somewhat differently depending on
           the relative risk of the leukemia recurring. Patients will be separated into "Standard
           Risk" and "High Risk".

        -  The treatment program for both groups is separated into 4 phases. The phases of
           treatment are induction, central nervous system (CNS) therapy, intensification and
           continuation.

        -  The induction phase of therapy lasts for about one month and its purpose is to kill all
           detectable leukemia cells. Patients in both groups will receive the following
           medication: prednisone, vincristine, doxorubicin, methotrexate, leucovorin,
           asparaginase, cytarabine (ARA-C), and hydrocortisone. Patients in the "Hight Risk" group
           will also receive dexrazoxane.

        -  Patients whose leukemia is found to have a specific genetic abnormality involving a gene
           on chromosome 11 (known as MLL gene) will have a MLL intensification phase which begins
           after complete remission and lasts about 1 month. The drugs involved in MLL
           intensification are: vincristine, methotrexate, leucovorin, hydrocortisone, cytarabine
           and L-asparaginase.

        -  CNS therapy begins immediately after the end of induction therapy, after remission is
           documented. This phase of treatment should last 3 weeks and includes a series of spinal
           taps with the instillation of anti-leukemia drugs. Four spinal taps will be performed
           over a two-week period. Both groups will receive vincristine, 6-mercaptopurine and
           methotrexate/cytarabine/hydrocortisone. Patients in the "High Risk" group will also
           receive doxorubicin with dexrazoxane.

        -  Radiation therapy will also be delivered to patients in the "High Risk" group during the
           CNS therapy phase. Radiation will be given in 8 daily treatments. The total dose of
           radiation used during this study is lower than what has been used in the past to help
           reduce side effects without increasing the risk of relapse.

        -  The intensification phase begins after the CNS therapy ends and lasts for 30 weeks. This
           phase is intended to further reduce the number of leukemia cells in the body and
           consists of cycles of chemotherapy repeated every three weeks with weekly shots of
           asparaginase. The drugs administered to both groups during this phase are: prednisone or
           dexamethasone, vincristine,6-mercaptopurine, methotrexate, E. coli asparaginase and
           cytarabine. Patients in the "High Risk" group will also receive doxorubicin and
           dexrazoxane.

        -  The continuation phase begins after the completion of the intensification phase and the
           goal is to eradicate all leukemia from the body. It consists of cycles of chemotherapy
           repeated every 3 weeks and is continued until the patient has been in remission for 2
           years. The drugs administered during this phase are vincristine, prednisone or
           dexamethasone, 6-mercaptopurine, methotrexate and cytarabine.

        -  During this trial there are two randomizations, each is between the "standard" treatment
           and the "investigational" treatment. One randomization involves the drug E. coli
           L-asparaginase and two ways of dosing this drug. One way is to give the same standard
           dose of the drug that has been administered for years. The other way is to start with a
           lower dose and measure the amount of the drug in the blood every 3 weeks adjusting the
           dose as necessary. The goal of doing this is to maintain adequate drug levels with lower
           doses in the hope the it may reduce some side effects of the drug.

        -  The second randomization involves the drugs prednisone and dexamethasone. Both drugs
           have been used in the past to help treat ALL but it is not known if there is a
           difference between the two drugs, especially in terms of side effects. Patients will be
           randomized to either receive dexamethasone or prednisone.

        -  Throughout the study blood tests, urine tests, spinal taps, and bone marrow tests will
           be performed to monitor the disease status, side effects from medications and other
           complications from therapy.

        -  Quality of life questionnaires will also be performed by the patient (if older than 8),
           parent and patient's clinician.
    

Intervention name(s): prednisone; dexamethasone; doxorubicin; E. coli asparaginase; vincristine; methotrexate; Leucovorin; Asparaginase; cytarabine; Methotrexate/Hydrocortisone
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): Induction Phase: Given orally or intravenously Days 0-28 Intensification Phase: Given orally Days 1-5 of each cycle Continuation Phase: Given orally Days 1-5 of each cycle; Intensification Phase: Given orally days 1-5 of each cycle Continuation Phase: Given orally days 1-5 pf each cycle; Induction Phase: Intravenously on Days 0,1 Intensification Phase: Intravenously on Day 1 of each cycle; Intensification Phase: In the muscle weekly. Dose will vary; Induction: Intravenously on days 0, 7, 14, 21 MLL Intensification Phase: Intravenously on Days 1, 8, 15, 22 CNS Therapy: Intravenously on Day 1 Intensification Phase: Intravenously on day 1 of each cycle Continuation Phase: Intravenously on Day 1 of each cycle; Induction: Intravenously on Day 2 MLL Intensification: Intravenously on Days 1, 8 Intensification: (when doxorubicin completed) Intravenously or into the muscle weekly Continuation: Intravenously or into the muscle weekly; Induction Phase: Intravenously or orally begins 36 hours after methotrexate MLL Intensification: Intravenously or orally begins 36 hours after methotrexate; Induction: Into the muscle on Day 4 MLL Intensification: Into the muscle on Days 16, 23; Induction: Intrathecal on Days 0, 14, 28 MLL Intensification: Intravenously on Days 15, 16, 22, 23; Induction: Intrathecal on Days 14, 28 MLL Intensification: Intrathecal on Days 2,9
Other intervention name(s): dexrazoxane; ARA-C
Intervention MeSH terms: Leucovorin; Cytarabine; Dexamethasone; Prednisone; Hydrocortisone; Doxorubicin; Methotrexate; Vincristine; Asparaginase; Dexrazoxane
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Acute lymphoblastic leukemia in children; High Risk ALL; Standard Risk ALL; E. coli asparaginase