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

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. Refractory, progressive or metastatic
pheochromocytoma/paraganglioma or related tumor.

- MIBG uptake: Tumors must be shown to be MIBG avid within 6 weeks prior to enrollment

- Age > 1 year and able to cooperate with radiation safety restrictions during therapy
period. Patients with pheochromocytoma/paraganglioma and related tumors must be
between 1 and 12 years of age.

- Life Expectancy: greater than 6 weeks.

- Lansky 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 10^6
cluster of differentiation 34 (CD34)+ cells/kg (optimum > 2 x 10^6 CD34+ cells/kg).
The minimum dose for bone marrow is 1.0 x 10^8 mononuclear cells/kg (optimum > 2.0 x
10^8 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 granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage
colony-stimulating factor (GM-CSF), interleukin-6 (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 and if cumulative 131I-MIBG dose will not exceed 60 mCi/kg.

- Organ Function

- Liver function: bilirubin <2x normal and aspartate aminotransferase (AST)/Alanine
aminotransferase (ALT) < 10x normal.

- Kidney function: Creatinine less than or equal to 2

- Hematopoietic Criteria Patients must have adequate hematopoietic function (without
transfusion): absolute neutrophil count (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 study chair 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.

- Patients with pheochromocytoma or paraganglioma who have any proteinuria on
urinalysis must have a 24-hr urine collection for protein. If there is proteinuria
above the reference range on a 24-hour urine collection, they are excluded due to
increased risk of respiratory complications.