Treatment of Acute Lymphoblastic Leukemia in Children
Condition: Drug/Agent Toxicity by Tissue/Organ; Leukemia
MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Drug-Related Side Effects and Adverse Reactions
Intervention: asparaginase; cyclophosphamide; cytarabine; dexamethasone; dexrazoxane hydrochloride; doxorubicin hydrochloride; etoposide; leucovorin calcium; mercaptopurine; methotrexate; methylprednisolone; pegaspargase; prednisolone; therapeutic hydrocortisone; vincristine sulfate; radiation therapy
Intervention description: Given IV; Given orally; Given IV
Intervention MeSH terms: Leucovorin; Cytarabine; Dexamethasone; Methylprednisolone; Prednisolone; Hydrocortisone; Hydrocortisone 17-butyrate 21-propionate; Hydrocortisone acetate; Hydrocortisone hemisuccinate; Cyclophosphamide; Doxorubicin; Liposomal doxorubicin; Methotrexate; Etoposide; Vincristine; Asparaginase; Mercaptopurine; Pegaspargase; Dexrazoxane; Razoxane; Levoleucovorin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 800.0
Sex: All
Minimum age: 1 Year
Maximum age: 18 Years
Healthy volunteers: No
Keywords: drug/agent toxicity by tissue/organ; untreated childhood acute lymphoblastic leukemia; L1 childhood acute lymphoblastic leukemia; L2 childhood acute lymphoblastic leukemia; T-cell childhood acute lymphoblastic leukemia

Summary:

      RATIONALE: L-asparaginase is an important component of treatment for childhood acute
      lymphoblastic leukemia, but is also associated with notable side-effects, including
      hypersensitivity, pancreatitis, and thrombosis. We have previously reported that patients
      with acute lymphoblastic leukemia in whom asparaginase treatment was discontinued because of
      intolerable side-effects had survival outcomes that were inferior to those who received all
      or nearly all of their intended doses. Two bacterial sources of asparaginase exist:
      Escherichia coli (E coli) and Erwinia chrysanthemia (Erwinia). Generally, the E coli-derived
      enzyme has been used as front-line therapy and the Erwinia-derived preparation has been
      reserved for patients who develop hypersensitivity reactions. Pegylated E coli asparaginase
      (PEG-asparaginase) has a longer half-life and is potentially less immunogenic than native E
      coli L-asparaginase, and has been used as the initial asparaginase preparation in some
      pediatric acute lymphoblastic leukemia treatment regimens.

      PURPOSE: Although the pharmacokinetics of each of these asparaginase preparations:
      intravenous PEG-asparaginase (IV-PEG) and intramuscular native E coli L-asparaginase (IM-EC)
      have been well characterized, their relative efficacy and toxicity have not been studied
      extensively.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Diagnosis of acute lymphoblastic leukemia (ALL)

               -  No known mature B-cell ALL, defined by the presence of any of the following:

                    -  Surface immunoglobulin

                    -  L3 morphology

                    -  t(8;14)(q24;q32)

                    -  t(8;22)

                    -  t(2;8)

               -  T-cell surface markers and t(8;14)(q24;q11) allowed

          -  No secondary ALL

        PATIENT CHARACTERISTICS:

          -  No known HIV positivity

          -  Not pregnant or nursing

          -  Fertile patients must use effective contraception

        PRIOR CONCURRENT THERAPY:

          -  No prior therapy except steroids of ≤ 1 week in duration and/or emergent radiation
             therapy to the mediastinum

               -  Patients treated with steroids within the past 7 days will not receive steroid
                  prophase during study treatment