N2001-03: CEP-701 in Treating Young Patients With Recurrent or Refractory High-Risk Neuroblastoma

DISEASE CHARACTERISTICS:

   - Diagnosis of neuroblastoma confirmed by at least 1 of the following:

      - Histology

      - Demonstrates clumps of tumor cells in the bone marrow with elevated urinary
      catecholamine metabolites

   - Recurrent or resistant/refractory disease

   - Neuroblastoma metastatic to the bone marrow with granulocytopenia, anemia, and/or
   thrombocytopenia allowed

   - High-risk disease

   - Patients in first response after completion of a prior front-line myeloablative
   regimen OR who were medically ineligible to receive a front-line myeloablative regimen
   must meet at least 1 of the following criteria:

      - Viable neuroblastoma determined by biopsy of a persistent lesion as seen on CT
      scan, MRI, or metaiodobenzylguanidine (MIBG) scan

         - If lesion was irradiated, biopsy must be performed at least 4 weeks after
         completion of prior radiotherapy

      - Morphologic evidence of tumor in bone marrow

   - Second or greater response (without histologic confirmation) allowed

   - Meets at least 1 of the following criteria:

      - At least 1 unidimensionally measurable lesion on CT scan, MRI, or X-ray

         - At least 20 mm by conventional techniques OR at least 10 mm by spiral CT
         scan

      - MIBG scan with positive uptake at a minimum of 1 site

      - Bone marrow with tumor cells on routine morphology (not by NSE staining only) of
      bilateral aspirate and/or biopsy AND/OR at least 5 tumor cells/10^6 mononuclear
      cells in the bone marrow by immunocytologic analysis of 2 consecutive bone
      marrows performed at least 1 day but no more than 4 weeks apart

PATIENT CHARACTERISTICS:

Age

   - 21 and under at diagnosis

Performance status

   - Karnofsky 50-100% (for patients > 16 years of age)

   - Lansky 50-100% (for patients ≤ 16 years of age)

Life expectancy

   - More than 2 months

Hematopoietic

   - See Disease Characteristics

   - Absolute neutrophil count ≥ 1,000/mm^3

   - Platelet count ≥ 50,000/mm^3 (transfusion independent)

   - Hemoglobin ≥ 8.0 g/dL (red blood cell transfusions allowed)

Hepatic

   - ALT and AST ≤ 3.0 times upper limit of normal (ULN)

   - Total bilirubin ≤ 1.5 times ULN

Renal

   - Creatinine ≤ 1.5 times normal OR

   - Creatinine clearance or radioisotope glomerular filtration rate ≥ 60 mL/min

Cardiovascular

   - Ejection fraction ≥ 50% by echocardiogram or MUGA OR

   - Fractional shortening ≥ 28% or above lower limit of normal by echocardiogram

Pulmonary

   - Lung function normal

   - No dyspnea at rest

   - No exercise intolerance

   - No supplemental oxygen requirement

Other

   - Not pregnant

   - Negative pregnancy test

   - Fertile patients must use effective contraception

   - No uncontrolled infection

   - No other concurrent illness that would preclude study treatment

PRIOR CONCURRENT THERAPY:

Biologic therapy

   - See Chemotherapy

   - At least 2 weeks since prior biologic or non-myelosuppressive therapy and recovered

   - More than 7 days since prior growth factors

   - No prior allogeneic stem cell transplantation AND no extensive chronic
   graft-versus-host disease

   - No concurrent growth factors except filgrastim (G-CSF) or sargramostim (GM-CSF)
   administered for neutropenia lasting for more than 7 days or for confirmed or clinical
   septicemia associated with neutropenia

Chemotherapy

   - At least 3 months since prior myeloablative chemotherapy with stem cell
   transplantation

   - At least 2 weeks since prior chemotherapy and recovered

Endocrine therapy

   - No concurrent corticosteroid therapy except replacement therapy for adrenal
   insufficiency or treatment for increased intracranial pressure

Radiotherapy

   - See Disease Characteristics

   - Recovered from prior radiotherapy

   - At least 6 weeks since prior therapeutic-dose MIBG

   - At least 6 weeks since prior craniospinal or other radiotherapy involving significant
   bone marrow (i.e., total pelvis or total abdomen)

   - At least 4 weeks since prior radiotherapy to any site biopsied

   - At least 2 weeks since prior local palliative radiotherapy (small port)

Surgery

   - Not specified

Other

   - No prior CEP-701

   - No concurrent administration of any of the following CYP3A4 inhibitors:

      - Cyclosporine

      - Clotrimazole

      - Ketoconazole

      - Erythromycin

      - Clarithromycin

      - Troleandomycin

      - HIV protease inhibitors

      - Nefazodone

      - Itraconazole

      - Voriconazole