Combination Chemotherapy in Treating Young Patients With Down Syndrome and Acute Myeloid Leukemia or Myelodysplastic Syndromes
Condition: Childhood Acute Basophilic Leukemia; Childhood Acute Eosinophilic Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Childhood Myelodysplastic Syndromes; de Novo Myelodysplastic Syndromes; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Neoplasm Metastasis; Leukemia, Monocytic, Acute; Leukemia, Myelomonocytic, Acute; Leukemia, Erythroblastic, Acute; Leukemia, Basophilic, Acute; Leukemia, Eosinophilic, Acute; Leukemia, Megakaryoblastic, Acute; Down Syndrome; Myelodysplastic Syndromes; Hypereosinophilic Syndrome; Syndrome
Intervention: asparaginase; daunorubicin hydrochloride; cytarabine; thioguanine; etoposide; laboratory biomarker analysis
Intervention description: Given IM; Given IV; Given IV or IT; Given orally; Given IV; Correlative studies
Intervention MeSH terms: Cytarabine; Etoposide; Daunorubicin; Etoposide phosphate; Asparaginase; Thioguanine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 205.0
Sex: All
Maximum age: 4 Years
Healthy volunteers: No

Summary:

      This phase III trial is studying how well combination chemotherapy works in treating young
      patients with Down syndrome and acute myeloid leukemia or myelodysplastic syndromes. Drugs
      used in chemotherapy work in different ways to stop the growth of cancer cells, either by
      killing the cells or by stopping them from dividing. Giving more than one drug (combination
      chemotherapy) may kill more cancer cells.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis DS or DS mosaicism by karyotype or chromosomal analysis

          -  Diagnosis of myelodysplastic syndromes (MDS) with < 30% blasts or acute myeloid
             leukemia (AML)

               -  Newly diagnosed disease

          -  Patients with a history of transient myeloproliferative disorder (TMD) are eligible
             provided the patient is diagnosed with AML or MDS at > 90 days of age AND meets either
             of the following criteria:

               -  At least 30% blasts in the bone marrow regardless of time since resolution of TMD

               -  More than 8 weeks since resolution of TMD with ≥ 5% blasts in the bone marrow

          -  Immunophenotype required for study entry

          -  No promyelocytic leukemia

          -  Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 50% by radionuclide
             angiogram

          -  Bilirubin ≤ 1.5 times upper limit of normal (ULN)

          -  AST or ALT < 2.5 times ULN

          -  Creatinine adjusted according to age as follows:

               -  No greater than 0.4 mg/dL (≤ 5 months)

               -  No greater than 0.5 mg/dL (6 months -11 months)

               -  No greater than 0.6 mg/dL (1 year-23 months)

               -  No greater than 0.8 mg/dL (2 years-5 years)

               -  No greater than 1.0 mg/dL (6 years-9 years)

               -  No greater than 1.2 mg/dL (10 years-12 years)

               -  No greater than 1.4 mg/dL (13 years and over [female])

               -  No greater than 1.5 mg/dL (13 years to 15 years [male])

               -  No greater than 1.7 mg/dL (16 years and over [male])

          -  Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min

          -  No evidence of dyspnea at rest

          -  No exercise intolerance

          -  Pulse oximetry > 94%

          -  No prior chemotherapy, radiotherapy, or any antileukemic therapy

               -  Intrathecal cytarabine therapy given at diagnosis allowed

          -  Prior therapy for TMD allowed