A Phase II Study Of hu14.18-IL2 In Children With Recurrent Or Refractory Neuroblastoma

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed neuroblastoma

- Relapsed or refractory to conventional therapy

- Measurable or evaluable disease documented by 1 of the following criteria:

- Clinical

- Radiographic

- Histologic

- MIBG scanning

- Immunocytochemistry

- No symptomatic pleural effusions or ascites requiring constant or intermittent
drainage

- No clinical or radiological evidence of CNS disease

PATIENT CHARACTERISTICS:

Age

- 21 and under

Performance status

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

- Lansky 50-100% (≤ 16 years of age)

Life expectancy

- At least 8 weeks

Hematopoietic

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

- Platelet count ≥ 75,000/mm^3*

- Must not be refractory to platelet transfusions

- Hemoglobin ≥ 9.0 g/dL* NOTE: *Transfusion allowed if patient is known to have a
history of bone marrow involvement with tumor

Hepatic

- ALT < 2.5 times upper limit of normal (ULN)

- Bilirubin ≤ 1.5 times ULN

- Hepatitis B surface antigen negative

Renal

- 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]) OR

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

Cardiovascular

- Shortening fraction ≥ 27% by echocardiogram OR

- Ejection fraction ≥ 50% by MUGA

- No symptomatic congestive heart failure

- No uncontrolled cardiac rhythm disturbance

Pulmonary

- Pulse oximetry > 94% on room air

- FVC > 80%

- FEV_1 > 80%

- No abnormal respiratory function

- No dyspnea at rest

- No exercise intolerance

- No prior history of ventilator support related to lung injury (e.g., pneumonia,
hemorrhagic pneumonitis, or capillary leakage)

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- HIV negative

- No active uncontrolled infection

- No active uncontrolled peptic ulcer

- No objective peripheral neuropathy ≥ grade 2

- No significant psychiatric disabilities

- No seizure disorders requiring antiseizure medications

- No other concurrent significant illness

PRIOR CONCURRENT THERAPY:

Biologic therapy

- Recovered from prior immunotherapy

- Prior in vivo monoclonal antibodies for biologic therapy or tumor imaging allowed
provided there is documented absence of detectable antibody to hu14.18 by serology

- More than 28 days since prior autologous stem cell transplantation

- Prior autologous marrow or stem cell infusion using monoclonal antibody-purged
specimens allowed

- More than 1 week since prior growth factors

- At least 7 days since prior nonmyelosuppressive biologic agents

- No prior allogeneic bone marrow or stem cell transplantation

- No concurrent immunomodulating agents

- No concurrent growth factors

Chemotherapy

- More than 3 weeks since prior myelosuppressive chemotherapy (4 weeks for
nitrosoureas) and recovered

- No concurrent anticancer chemotherapy

Endocrine therapy

- No concurrent corticosteroids except 100 mg or less of hydrocortisone (or equivalent)
as premedication for blood transfusion or treatment for transfusion reaction

- No other use of systemic steroids

Radiotherapy

- Recovered from prior radiotherapy

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

- At least 6 months since prior craniospinal radiotherapy

- At least 6 months since prior total body irradiation

- At least 6 months since prior radiotherapy to ≥ 50% of the pelvis

- At least 6 weeks since other prior substantial bone marrow radiotherapy

- Concurrent radiotherapy to localized painful lesions allowed provided at least 1
measurable or evaluable lesion is not irradiated

Surgery

- More than 2 weeks since prior major surgery (e.g., laparotomy or thoracotomy)

- No prior organ allografts

Other

- No concurrent immunosuppressive drugs

- No other concurrent myelosuppressive antineoplastic drugs