131I-Labeled MIBG for Refractory Neuroblastoma: A Compassionate Use Protocol

Neuroblastoma remains a fatal disease for a large percentage of patients, especially those
with high-risk disease features who become resistant to conventional therapy.
131I-metaiodobenzylguanidine (131I-MIBG) is a norepinephrine analog that concentrates in
adrenergic tissue and therefore holds promise for cell-specific treatment of neuroblastoma.
131I-MIBG is active against relapsed or refractory neuroblastoma and associated hematopoietic
toxicity can be abrogated with autologous stem cell rescue. 131I-MIBG given in doses of 10-18
mCi/kg with stem cell rescue, if necessary, is safe and effective palliative therapy for
refractory or relapsed neuroblastoma patients.

Inclusion Criteria:

- Diagnosis: Refractory or relapsed neuroblastoma with original diagnosis based on tumor
histopathology or elevated urine catecholamines with typical tumor cells in the bone
marrow.

- Age > 1 year and able to cooperate with radiation safety restrictions during therapy
period.

- Life Expectancy: greater than 6 weeks.

- Lanksy and Karnofsky Performance Status: 60% or higher.

- Disease status: Failure to respond to standard therapy (usually combination
chemotherapy with or without radiation and surgery) or development of progressive
disease at any time (any new lesion or an increase in size of >25% of a pre-existing
lesion). Disease evaluable by MIBG scan must be present within 6 weeks of study entry
and subsequent to any intervening therapy.

- Stem cells: Patients must have an autologous hematopoietic stem cell product available
for re-infusion after MIBG treatment at doses of >12 mCi/kg if needed. The minimum
quantity for purged or unpurged peripheral blood stem cells is 1.0 x 106 CD34+
cells/kg (optimum > 2 x 106 CD34+ cells/kg). The minimum dose for bone marrow is 1.0 x
108 mononuclear cells/kg (optimum > 2.0 x 108 mononuclear cells/kg). If no stem cells
are available, then the dose of 131I-MIBG should be <12 mCi/kg .

- Prior Therapy: Patients may enter this study with or without re-induction therapy for
recurrent tumor. Patients must have fully recovered from the toxic effects of any
prior therapy. At least 2 weeks should have elapsed since any anti-tumor therapy and
the patient must meet hematologic criteria below. Three months should have elapsed in
the case of completing radiation to any of the following fields: craniospinal, total
abdominal, whole lung, total body irradiation). Cytokine therapy (eg G-CSF, GM-CSF,
IL-6, erythropoietin) must be discontinued a minimum or 24 hours prior to MIBG
therapy. Prior 131I-MIBG therapy is allowed if > 6 months previous and if the patient
has adequate hematopoietic stem cells available.

- Organ Function

- Liver function: bilirubin <2x normal and AST/ALT < 10x normal.

- Kidney function: Creatinine less than or equal to 2

- Hematopoietic Criteria Patients must have adequate hematopoietic function (without
transfusion): ANC >.750 x 10E9/L; Platelets >50 x 10E9/L if stem cells are not
available; if stem cells are available, the patient should be independent of platelet
transfusions with a platelet count of at least 20 x 10E9/L. Hemoglobin >10g/dl at time
of treatment (transfusion allowed). Patients with granulocytopenia and/or
thrombocytopenia due to tumor metastatic to the bone marrow may be eligible after
discussion with Dr. Matthay or designee.

- Normal lung function as manifested by no dyspnea at rest or exercise intolerance, no
oxygen requirement.

- No clinically significant cardiac dysfunction

- Signed informed consent: The patient and/or the patient's legally authorized guardian
must acknowledge in writing that consent to become a study subject has been obtained,
in accordance with institutional policies approved by the U.S. Department of Health
and Human Services.

Exclusion Criteria:

- Patients with disease of any major organ system that would compromise their ability to
withstand therapy. Any significant organ impairment should be discussed with the Study
Chair or Vice Chair prior to patient entry.

- Because of the teratogenic potential of the study medications, no patients who are
pregnant or lactating will be allowed. Patients of childbearing potential must
practice an effective method of birth control while participating on this study, to
avoid possible pregnancy.

- Patients who are on hemodialysis.

- Patients with active infections that meet grade 3-4 toxicity criteria.