MIBG for Refractory Neuroblastoma and Pheochromocytoma

Primary Objective is to provide access to therapy with 131I-MIBG for patients with
relapsed/refractory neuroblastoma or metastatic pheochromocytoma.

Secondary Objective is to assess disease response to 131I-MIBG therapy for patients with
relapsed/refractory neuroblastoma or metastatic pheochromocytoma.

Tertiary Objectives are to 1) gain more information about the toxicities of 131I-MIBG
therapy; 2) assess improvement of symptoms, including pain and fatigue, for patients with
relapsed/refractory neuroblastoma or metastatic pheochromocytoma who are receiving 131I-MIBG
therapy.

- The therapeutic dose of 131I-MIBG will be based on the following:

1. Minimum dose of 10 mCi/kg for patients without a stem cell source whose renal
function is above the upper limit of normal but still meets eligibility criteria.

2. Dose of 12 mCi/kg for patients without a stem cell source with normal renal
function and meets other eligibility criteria.

3. Dose of > 12 mCi/kg to 18 mCi/kg maximum at investigator's discretion for patients
meeting eligibility criteria with stem cells available.

- A urinary catheter and intravenous fluids will be used for bladder protection, and
potassium iodide solution for thyroid Protection.

- G-CSF is recommended for patients with ANC less than 750 after MIBG infusion.

- hematopoietic stem cell infusion is recommended for patients with grade 4 hematologic
toxicity following 131I-MIBG therapy that continues to have an ANC <200 on G-CSF without
signs of recovery for >2 weeks and any patient requiring platelet transfusion more than
two times weekly for 4 consecutive weeks.

- Follow-up will be done until disease progression, death or other therapies are
initiated.

Inclusion Criteria:

- Diagnosis:

- Relapsed/refractory neuroblastoma with original diagnosis based on tumor
histopathology or elevated urine catecholamines with typical neuroblastoma cells
in the bone marrow

- Metastatic pheochromocytoma

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

- Karnofsky or Lansky performance status of ≥ 50%

- Life expectancy: ≥ at least 8 weeks

- Disease status: Failure to respond to standard therapy or development of progressive
disease at any time.

- Disease must be evaluable by MIBG scan. A positive MIBG scan must be present within 8
weeks prior to study entry and subsequent to any intervening therapy. If the patient
has only one MIBG positive lesion and that lesion was radiated, a biopsy must be done
at least 4 weeks after radiation was completed and must show viable neuroblastoma.

- Stem Cells: Patients must have a hematopoietic stem cell product available for
reinfusion after MIBG treatment at doses of > 12 mCi/kg.

- Have acceptable organ function as defined below within 7 days of enrollment:

- Bone Marrow: ANC ≥750 X 109 /L and platelets ≥50,000 X 109 /L without transfusion
if stem cells are not available (any ANC or platelet allowed if stem cells
available)

- Renal: Creatinine ≤3x upper limit of normal

- Hepatic: Bilirubin ≤2x upper limit of normal; AST/ALT ≤10x upper limit of normal

- Cardiac: Ejection fraction ≥45% on echocardiogram

- Pulmonary: normal lung function as manifested by no dyspnea and/or oxygen
saturation ≥ 88% on room air.

- Prior Therapy: Patients must have recovered from all acute toxicities (defined as
CTCAE 4.0 ≤ grade 1) associated with any prior therapy, and:

- Myelosuppressive chemotherapy: At least 2 weeks should have elapsed since any
chemotherapy causing myelosuppression

- Biologic (anti-neoplastic agent): At least 7 days should have elapsed since the
completion of therapy with a biologic agent.

- Monoclonal antibodies: At least 3 half-lives should have elapsed since therapy
with a monoclonal antibody

- Radiation therapy: 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). For all other sites of radiation, at least 2 weeks
should have relapsed.

- Cytokine therapy (e.g. G-CSF, GM-CSF, IL-6, IL-2): must be discontinued a minimum
of 24 hours prior to MIBG therapy.

- Voluntary written informed consent

Exclusion Criteria:

- Patients with disease of any major organ system that would compromise their ability to
withstand therapy.

- Because of the teratogenic potential of the study medication, 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 damage to the fetus.

- Known allergy to any of the agents or their ingredients used in this study.

- Patients who are on hemodialysis

- Patients with untreated positive blood cultures or progressive infections as assessed
by radiographic studies