RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Oblimersen may increase the effectiveness of doxorubicin and cyclophosphamide by making the tumor cells more sensitive to the drug. Chemoprotective drugs such as dexrazoxane may protect normal cells from the side effects of chemotherapy.

PURPOSE: Phase I trial to study the effectiveness of oblimersen plus combination chemotherapy and dexrazoxane in treating children and adolescents who have relapsed or refractory solid tumors.

OBJECTIVES:

• Determine the dose-limiting toxic effects and recommended phase II dose of oblimersen when combined with cyclophosphamide, doxorubicin, and dexrazoxane in pediatric patients with relapsed or refractory solid tumors.
• Determine the pharmacokinetic behavior of this regimen in these patients.
• Determine, preliminarily, the antitumor activity of oblimersen in these patients.
• Assess the biologic activity of oblimersen in mononuclear cells and tumor tissues, in terms of bcl-2 and related protein expression, in these patients.

OUTLINE: This is a 2-part, multicenter, dose-escalation study.

• Part A: Patients receive oblimersen IV continuously on days 1-7. Patients also receive dexrazoxane IV followed by doxorubicin IV over 15 minutes followed by cyclophosphamide IV over 1 hour on days 5 and 6. Filgrastim (G-CSF) is administered subcutaneously once daily beginning on day 8 and continuing until blood counts recover. Treatment repeats every 21 days for up to 18 courses (1 year) in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease whose shortening fraction falls below 28% by echocardiogram or whose total life-time cumulative anthracycline dose exceeds 750 mg/m^2 may receive additional courses of oblimersen and cyclophosphamide without doxorubicin and dexrazoxane.

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

• Part B: Patients receive oblimersen at the MTD determined in part A and escalating doses of dexrazoxane, doxorubicin, and cyclophosphamide on the same treatment schedule as in part A.

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

Patients are followed for survival.

PROJECTED ACCRUAL: A total of 12-15 patients will be accrued for this study within 1-2 years.

• Cardiac Toxicity
• Unspecified Childhood Solid Tumor, Protocol Specific

• Biological: filgrastim
• Biological: oblimersen sodium
• Drug: cyclophosphamide
• Drug: dexrazoxane hydrochloride
• Drug: doxorubicin hydrochloride

DISEASE CHARACTERISTICS:

• Histologically confirmed solid tumor at original diagnosis that has failed standard therapy or for which no standard therapy exists

  • Patients must have a disease for which there is no known curative potential

• Patients must meet the following criteria for bone marrow function:

  • Status post stem cell transplantation (SCT)
  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3 (transfusion independent)
  • Hemoglobin at least 8.0 g/dL (RBC transfusions allowed)
• No lymphomas
• No CNS tumors or known metastatic disease to the brain or spinal cord

PATIENT CHARACTERISTICS:

Age:

• 1 to 21

Performance status:

• Karnofsky 50-100% (age 11 to 21)
• Lansky 50-100% (age 1 to 10)

Life expectancy:

• At least 8 weeks

Hematopoietic:

• See Disease Characteristics

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• ALT no greater than 3 times ULN
• No significant hepatic dysfunction

Renal:

• Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min OR

• Creatinine, based on age, as follows:

  • Age 1 to 5: no greater than 0.8 mg/dL
  • Age 6 to 10: no greater than 1.0 mg/dL
  • Age 11 to 15: no greater than 1.2 mg/dL
  • Age 16 to 21: no greater than 1.5 mg/dL
• No significant renal dysfunction

Cardiovascular:

• Shortening fraction at least 28% by echocardiogram OR
• Ejection fraction at least 45% by MUGA

Pulmonary:

• No significant pulmonary dysfunction

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No serious uncontrolled infections
• No other end-organ dysfunction that would preclude study entry
• No other clinically significant systemic illness

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics
• Recovered from prior immunotherapy
• At least 1 week since prior growth factors or other biologic agents
• At least 6 months since prior autologous SCT
• At least 6 months since prior allogeneic bone marrow transplantation and recovered with no evidence of graft-versus-host disease
• No concurrent immunomodulating agents
• No concurrent prophylactic growth factors during the first course of the study
• No concurrent immunotherapy or other biologic therapy

Chemotherapy:

• Recovered from prior chemotherapy
• At least 2 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas)
• No prior life-time cumulative doxorubicin dose of more than 450 mg/m^2 or equivalent
• No other concurrent chemotherapy

Endocrine therapy:

• Concurrent chronic steroids allowed

Radiotherapy:

• Recovered from prior radiotherapy
• More than 2 weeks since prior localized palliative radiotherapy (small port)
• More than 6 months since prior substantial radiotherapy to bone marrow (craniospinal radiotherapy, total body irradiation, or hemi-pelvic radiotherapy)
• No concurrent radiotherapy

Surgery:

• Not specified

Other:

• Concurrent chronic medications (e.g., narcotics or antiepileptics) allowed
• No other concurrent investigational agents
• No other concurrent cancer therapy