A Phase I/IB Intergroup Trial of the HU14.18-IL2 Fusion Protein in Children With Refractory Neuroblastoma and Other GD2 Positive Tumors

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed neuroblastoma or melanoma at original diagnosis

- Refractory to chemotherapy or recurrence after prior multiagent chemotherapy

- Measurable or evaluable (detectable by bone scan) metastatic disease OR

- No evidence of disease if complete response to prior surgical resection,
radiotherapy, and/or chemotherapy OR

- Histologically confirmed tumor expressing GD2 antigen at original diagnosis or
relapse

- Refractory to standard treatment

- Measurable or evaluable disease by clinical assessments or laboratory markers OR

- No evidence of disease after prior surgical resection of metastatic, recurrent
disease

- Histologically confirmed recurrent osteogenic sarcoma after prior chemotherapy
allowed

- Soft tissue sarcoma allowed

- No primary CNS tumors

- Prior CNS metastases allowed, provided:

- Disease previously treated

- Disease clinically stable for 4 weeks before study

- At least 4 weeks since prior steroids for CNS metastases

- No clinically detectable pleural effusions or ascites

PATIENT CHARACTERISTICS:

Age:

- 21 and under

Performance status:

- Karnofsky 60-100% for children over age 10

- Lansky 60-100% for children age 10 and under

Life expectancy:

- At least 12 weeks

Hematopoietic:

- Absolute neutrophil count greater than 1,000/mm^3

- Platelet count at least 75,000/mm^3 (transfusion allowed)

- Hemoglobin at least 9.0 g/dL (transfusion allowed)

Hepatic:

- Bilirubin less than 1.5 mg/dL

- ALT or AST no greater than 2.5 times normal

- Hepatitis B surface antigen negative

Renal:

- Creatinine no greater than 1.5 mg/dL OR

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

Cardiovascular:

- Shortening fraction at least 27% by echocardiogram OR

- Ejection fraction more than 50% by MUGA scan

- No congestive heart failure

- No uncontrolled cardiac rhythm disturbance

Pulmonary:

- FEV_1 and FVC more than 60% of predicted OR

- No dyspnea at rest

- No exercise intolerance

- Oxygen saturation more than 94% by pulse oximetry on room air

Neurologic:

- No seizure disorders requiring antiseizure medications

- No significant neurologic deficit or grade 2 or greater objective peripheral
neuropathy

Other:

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- HIV negative

- No significant concurrent illnesses unrelated to cancer or its treatment

- No significant psychiatric disabilities

- No uncontrolled active infections

- No uncontrolled active peptic ulcer

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- At least 1 week since prior growth factors

- At least 1 week since prior immunomodulatory therapy

- Prior monoclonal antibodies allowed if no detectable antibody to hu14.18

- Prior autologous bone marrow transplantation (BMT) or stem cell transplantation (SCT)
allowed

- Prior autologous BMT or SCT with monoclonal antibody-purged specimens allowed

- No concurrent growth factors

- No concurrent interferon

Chemotherapy:

- See Disease Characteristics

- At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas, mitomycin, or
melphalan)

- No concurrent palliative chemotherapy

Endocrine therapy:

- See Disease Characteristics

- At least 2 weeks since prior glucocorticoids, except for life-threatening symptoms

- No concurrent corticosteroids

- No concurrent glucocorticoids, except for life-threatening symptoms

Radiotherapy:

- See Disease Characteristics

- At least 3 weeks since prior radiotherapy

- No concurrent palliative radiotherapy

Surgery:

- See Disease Characteristics

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

- No prior organ allografts

- No concurrent palliative surgery

Other:

- Recovered from prior therapy

- At least 1 week since prior tretinoin

- At least 3 weeks since prior immunosuppressive therapy

- No other concurrent immunosuppressive drugs