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.

- 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.