A Phase I Investigation of IL-12 (NSC 672423)/Pulse IL-2 (Aldesleukin) in Children With Persistent and/or Refractory Neuroblastoma (13623)

Inclusion Criteria:

- Diagnosis of neuroblastoma

- Histologically confirmed disease AND/OR disease defined by tumor cells in the
bone marrow and elevated urinary catecholamine metabolites

- Persistent and/or refractory disease, with at least 1 of the following:

- Biopsy-proven residual disease at least 12 weeks after myeloablative therapy

- Progressive disease after nonmyeloablative or myeloablative therapy

- Recurrent disease, evidenced by any of the following:

- Biopsy-proven recurrent soft tissue disease

- Metaiodobenzylguanidine (MIBG)-positive lesions visible on any other imaging
modality or repeat MIBG obtained 2-4 weeks or more apart

- Histologically confirmed bone marrow disease

- Progressive or stable disease after at least 1 prior standard salvage regime

- No clinically significant pleural effusion

- ECOG 0-1

- Life expectancy >= 12 weeks

- Hepatitis A antibody negative

- Hepatitis B surface antigen negative

- Positive hepatitis B titer allowed if patient has been immunized and has no
history of disease

- Hepatitis C virus negative

- No history of congenital or acquired coagulation disorder

- Cardiac function normal by ECG

- No dyspnea at rest

- No exercise intolerance

- Oxygen saturation at least 94% by pulse oximetry

- DLCO greater than 60% of predicted

- FEV1 greater than 70% of predicted

- Negative pregnancy test

- Skull-based bony lesions without space-occupying intracranial extension are allowed

- No prior or concurrent intracranial metastatic disease to the brain parenchyma

- Not pregnant or nursing

- Fertile patients must use effective barrier contraception during and for at least 2
months after study

- No prior hematologic malignancy (including leukemia or lymphoma)

- No history of malignant hyperthermia

- No prior or concurrent autoimmune disease

- No positive direct Coombs testing

- No history of ongoing or intermittent bowel obstruction

- No active infection or other significant systemic illness

- More than 2 weeks since prior fenretinide

- More than 2 weeks since prior 13-cis-retinoic acid

- More than 2 weeks since prior filgrastim (G-CSF) or sargramostim (GM-CSF)

- More than 2 weeks since prior interferons or interleukins

- More than 2 weeks since prior cytokine-fusion proteins

- More than 2 weeks since prior IV immunoglobulin (IVIG)

- No prior interleukin-12

- No concurrent cytokines

- No concurrent fenretinide

- No concurrent 13-cis-retinoic acid

- No other concurrent immunomodulators, including:

- G-CSF and GM-CSF

- Interferons

- Other interleukins

- IVIG

- More than 4 weeks since prior chemotherapy

- No other unstable medical condition or critical illness that would preclude study
participation

- More than 12 weeks since prior myeloablative chemotherapy followed by autologous stem
cell transplantation:

No prior myeloablative chemotherapy followed by allogeneic bone marrow transplantation

- More than 2 weeks since prior growth hormones

- More than 4 weeks since prior systemic corticosteroids

- More than 2 weeks since prior non-corticosteroid hormonal therapy (including oral
birth control pills)

- No concurrent hormonal therapy (including oral birth control pills)

- No concurrent growth hormones

- No concurrent systemic corticosteroids, except for use in life-threatening
complications

- More than 4 weeks since prior radiotherapy

- No prior solid organ transplantation

- More than 4 weeks since prior investigational agents

- No other concurrent investigational agents

- No prior enrollment on COG-A3973, unless disease has progressed

- No history of hemolytic anemia

- Absolute neutrophil count at least 1,500/mm^3 [Note: Independent of growth factor or
transfusion support]

- Platelet count at least 75,000/mm^3 [Note: Independent of growth factor or
transfusion support]

- AST and ALT less than 2.5 times upper limit of normal

- Bilirubin less than 2.0 mg/dL

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

- HIV negative

- Ejection fraction at least 50% by echocardiogram or MUGA OR Fractional shortening at
least 30% by echocardiogram

- No congestive heart failure

- No uncontrolled cardiac arrhythmia