Decitabine, Doxorubicin, and Cyclophosphamide in Treating Children With Relapsed or Refractory Solid Tumors or Neuroblastoma

Inclusion Criteria:

• Histologically confirmed diagnosis of either of the following:

  • Solid tumor (part A)

    • No lymphoma

  • Neuroblastoma (part B)

    • Original diagnosis may be based on elevated urine vanillylmandelic acid (VMA) and homovanillic acid (HVA) and bone marrow examination

    • Accessible disease by bone marrow aspirate or tumor biopsy

      • No laparotomy, thoracotomy, endoscopy, or craniotomy for biopsy
• No known curative therapy OR therapy proven to prolong survival with an acceptable quality of life available
• No known brain or spinal cord metastases
• No CNS tumors
• Performance status - Karnofsky 50-100% (patients 11 to 21 years of age)
• Performance status - Lansky 50-100% (patients ≤ 10 years of age)

• Parts A and B without bone marrow infiltration:

  • Absolute neutrophil count ≥ 1,000/mm^3
  • Platelet count ≥ 100,000/mm^3 (transfusion independent)

• Part B with bone marrow infiltration (i.e., tumor metastatic to bone marrow with granulocytopenia, anemia, and/or thrombocytopenia):

  • Absolute neutrophil count ≥ 750/mm^3
  • Platelet count ≥ 50,000/mm^3 (transfusion independent)
• Hemoglobin ≥ 8.0 g/dL (transfusion allowed)
• No sickle cell anemia
• Bilirubin ≤ 1.5 mg/dL
• ALT ≤ 5 times upper limit of normal
• No significant hepatic dysfunction that would compromise the tolerability of decitabine or interfere with study procedures or results

• Creatinine based on age as follows:

  • ≤ 0.8 mg/dL (5 years of age and under)
  • ≤ 1.0 mg/dL (6 to 10 years of age)
  • ≤ 1.2 mg/dL (11 to 15 years of age)
  • ≤ 1.5 mg/dL (16 to 21 years of age)
• Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min
• No significant renal dysfunction that would compromise the tolerability of decitabine or interfere with study procedures or results
• Shortening fraction ≥ 28% by echocardiogram
• Ejection fraction of ≥ 45% by MUGA
• No significant pulmonary dysfunction that would compromise the tolerability of decitabine or interfere with study procedures or results
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No prior allergic reaction attributed to compounds of similar chemical or biological composition to agents used in this study
• No uncontrolled serious infection
• No significant end-organ dysfunction that would compromise the tolerability of decitabine or interfere with study procedures or results
• Recovered from prior immunotherapy
• At least 7 days since prior biologic therapy
• More than 1 week since prior growth factor therapy (2 weeks for pegfilgrastim)
• More than 2 weeks since prior epoetin alfa
• At least 6 months since prior autologous stem cell transplantation

• At least 6 months since prior allogeneic bone marrow transplantation

  • Patients must have full organ recovery and no evidence of graft-versus-host disease
• No concurrent immunomodulating agents
• No concurrent immunotherapy
• No concurrent biologic therapy
• No concurrent epoetin alfa
• Recovered from prior chemotherapy
• More than 2 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas)
• Prior total lifetime cumulative anthracycline dose ≤ 450 mg/m^2 of doxorubicin or equivalent
• No other concurrent chemotherapy
• No concurrent hydroxyurea
• Recovered from prior radiotherapy
• More than 2 weeks since prior local palliative small port radiotherapy
• More than 6 months since prior substantial bone marrow irradiation (e.g., cranio-spinal irradiation, total body irradiation, or hemi-pelvic irradiation)
• No concurrent radiotherapy
• No other concurrent anticancer therapy
• No other concurrent investigational agents
• Concurrent oral iron supplementation for patients with a known iron deficiency or a microcytic hypochromic anemia allowed