131I-Metaiodobenzylguanidine (131I-MIBG) Therapy for Relapsed/Refractory Neuroblastoma

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

Secondary Objectives are to (1) assess disease response to 131I-MIBG therapy for patients
with relapsed/refractory neuroblastoma or metastatic pheochromocytoma; (2) gain more
information about the toxicities of 131I-MIBG therapy; and (3) assess improvement of
symptoms, including pain and fatigue, for patients with relapsed/refractory neuroblastoma or
metastatic pheochromocytoma who are receiving 131I-MIBG therapy.

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: patients must have a life expectancy of at least 8 weeks

- Disease status: Failure to respond to standard therapy (usually combination
chemotherapy with or without radiation and surgery) or development of progressive
disease at any phase of standard therapy (any new lesion or an increase in size >25%
of a pre-existing lesion). Patients may enter this study with or without re-induction
therapy for recurrent tumor.

- 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: If a patient does not have a hematopoietic stem cell product available for
re-infusion after MIBG treatment, they may not receive a 131IMIBG dose >12 mCi/kg.
Patients must have a hematopoietic stem cell product available for re-infusion after
MIBG treatment at doses of > 12 mCi/kg. The minimum quantity for peripheral blood stem
cells is 1.5 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).

- Stem cell source: The patients on this protocol will have autologous PBSCs available.

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

- Bone Marrow: ANC ≥750 X 109 /L, platelets ≥50,000 X 109 /L, and hemoglobin ≥ 8.0 g/dL
without transfusion if stem cells are not available. ANC ≥500 X 109 /L, platelets
≥20,000 X 109 /L, and hemoglobin ≥ 8.0 g/dL with transfusions allowed if stem cells
are available. Patients with stem cells available are excluded if they require two
platelet transfusions per week to maintain the minimum required platelet count. A bone
marrow examination is not medically indicated for patients diagnosed with metastatic
pheochromocytoma.

- Renal: Creatinine ≤ 2 times upper limit of normal

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

- Cardiac: Ejection fraction ≥ 45% on echocardiogram or shortening fraction

>/=27%

- Pulmonary: normal lung function as manifested by no dyspnea and/or oxygen saturation ≥
94% on room air.

- Prior Therapy: Patients must have recovered from all acute toxicities (defined as
CTCAE 5.0 ≤ 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 elapsed.

- 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 must be obtained before performance of any
study-related procedure not part of normal medical care, with the understanding that
consent may be withdrawn by the subject at any time without prejudice to future
medical care.

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

- Patients who have had prior treatment with 131I-MIBG who do not meet the re-treatment
criteria.

- In patients with metastatic pheochromocytoma, screening urinalysis required prior to
study enrollment. If random collection urine specimen is positive for proteinuria,
patients must have 24-hour urine protein determination. Patients with metastatic
pheochromocytoma are excluded if 24-hour urine protein is above the institutional
upper limit of normal.

- Patients with known MIBG-avid parenchymal brain metastases are excluded.