RATIONALE: Drugs used in chemotherapy, such as decitabine, doxorubicin, and cyclophosphamide, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of decitabine when given together with doxorubicin and cyclophosphamide in treating children with relapsed or refractory solid tumors or neuroblastoma.

OBJECTIVES:

Primary

• Determine the maximum tolerated dose of decitabine in combination with doxorubicin and cyclophosphamide in children with relapsed or refractory solid tumors or neuroblastoma.
• Determine the toxic effects of this regimen in these patients.
• Determine whether decitabine induces tumor caspase-8 demethylation and expression in these patients.

Secondary

• Determine the pharmacokinetics of low-dose decitabine in these patients.
• Determine the biological and clinical response in patients treated with this regimen.
• Compare patterns of peripheral blood gene expression, using gene expression profiling, in patients before and after treatment with decitabine.

OUTLINE: This is a multicenter, dose-escalation study of decitabine.

• Part A (solid tumor patients): Patients receive decitabine IV over 1 hour on days 0-6 and doxorubicin IV over 15 minutes and cyclophosphamide IV over 1 hour on day 7. Patients then receive filgrastim (G-CSF) subcutaneously (SC) beginning on day 8 and continuing until blood counts recover OR pegfilgrastim SC once on day 8 or 9*. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of decitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

NOTE: *For patients > 45 kg

• Part B (neuroblastoma patients): Once the MTD is determined for part A, patients are treated as in part A at the MTD .

Patients are followed at 30 days.

PROJECTED ACCRUAL: A total of 15-21 patients will be accrued for this study within 1-2 years.

• Neuroblastoma
• Unspecified Childhood Solid Tumor, Protocol Specific

• Biological: filgrastim
• Biological: pegfilgrastim
• Drug: cyclophosphamide
• Drug: decitabine
• Drug: doxorubicin hydrochloride

DISEASE CHARACTERISTICS:

• 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

PATIENT CHARACTERISTICS:

Age

• Over 12 months to 21 years

Performance status

• Karnofsky 50-100% (patients 11 to 21 years of age)
• Lansky 50-100% (patients ≤ 10 years of age)

Life expectancy

• Not specified

Hematopoietic

• 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

Hepatic

• 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

Renal

• 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) OR
• 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

Cardiovascular

• Shortening fraction ≥ 28% by echocardiogram OR
• Ejection fraction of ≥ 45% by MUGA

Pulmonary

• No significant pulmonary dysfunction that would compromise the tolerability of decitabine or interfere with study procedures or results

Other

• 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

PRIOR CONCURRENT THERAPY:

Biologic therapy

• 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

Chemotherapy

• 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

Endocrine therapy

• Not specified

Radiotherapy

• 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

Surgery

• Not specified

Other

• 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