Expanded Access Protocol Using 131I-MIBG

INCLUSION CRITERIA:

1. Diagnosis: Refractory or relapsed neuroblastoma with original diagnosis based on
tumor histopathology or elevated urine catecholamines with typical tumor cells in
the bone marrow, OR pheochromocytoma or paraganglioma (less than 12 years of age)
not amenable to curative surgery.

2. Age ≥12 months and able to cooperate with radiation safety restrictions during
therapy period with/without pharmacologic anxiolysis.

3. 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 evaluation must be completed within 8 weeks of study entry. If
possible, the disease evaluation should take place subsequent to any intervening
therapy; if intervening therapy does occur, evaluations should be done as clinically
indicated. If patient has received prior treatment with MIBG, they must have a
response or stable disease after the most recent MIBG infusion. Patient may have PD
after showing an initial response to MIBG therapy (at [or around] the day 35-63
post-MIBG therapy evaluation).

4. Stem cells: Patients must have a hematopoietic stem cell product available for
re-infusion after 131I-MIBG treatment at doses of 12 mCi/kg. If no stem cells are
available, then the dose of 131I-MIBG should be <12 mCi/kg.

5. 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, meeting the following criteria:

1. At least 2 weeks should have elapsed since any anti-tumor therapy and the
patient must meet certain hematologic criteria.

2. 3 months should have elapsed in the case of completing external beam radiation
for total abdominal, whole lung, total body irradiation (spot irradiation to
skull-based metastases is NOT a contraindication). Patients who receive
localized emergency radiation to sites of life-threatening or
function-threatening disease prior to or immediately after establishment of the
definitive diagnosis are not contraindicated for treatment on this protocol.

3. Cytokine therapy (e.g. G-CSF, GM-CSF, IL-6, erythropoietin) must be
discontinued a minimum of 24 hours prior to 131I-MIBG therapy.

4. Minimum of six weeks from previous 131I-MIBG therapy.

5. The lifetime cumulative injected activity should be evaluated by the
Investigator on a case-by-case basis with special attention to any recovery
from past 131I-MIBG dose(s).

6. For patients who received a stem cell infusion for a previous 131I-MIBG therapy
but do NOT have remaining stored stem cells:

i. If the stem cell reinfusion was protocol driven but not based upon the
development of profound cytopenias (e.g. automatic stem cell reinfusion on Day 14),
the patient is eligible for retreatment with MIBG at a dose <12 mCi/kg at the
investigators discretion; ii. If the stem cell reinfusion was given based upon the
development of profound cytopenias, decisions for re-treatment with 131I-MIBG will
require a case-by-case evaluation by the Investigator.

6. Organ Function:

1. Liver function: Bilirubin ≤ 2x upper limit of normal; AST/ALT ≤ 10x upper limit
of normal.

2. Kidney function:

i. Serum Creatinine ≤ 2x upper limit of normal OR ii. 24-hr creatinine clearance OR
GFR ≥ 60 ml/min/1.73m2.

c. Hematologic Criteria: ANC ≥750/uL; Platelets ≥ 50,000/uL without transfusion if
stem cells are not available (ANC ≥ 500 and any platelet count allowed if stem cells
available). Patient must be off myeloid growth factors for at least 24 hours. If the
patient has received prior treatment with MIBG, they may be thrombocytopenic, but
requiring no more than 2 platelet transfusions per week to maintain counts above
20,000/uL. Hemoglobin must be ≥ 10gm/dL (transfusion allowed) regardless of stored
stem cell availability.

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

e. No clinically significant cardiac dysfunction.

7. Signed informed consent/assent has been obtained.

EXCLUSION CRITERIA:

1. Patients 12 years and older with iobenguane scan positive, unresectable, locally
advanced or metastatic pheochromocytoma or paraganglioma and marketed product is
available.

2. Patients eligible for the Phase II (OPTIMUM) trial.

3. 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
Principal Investigator prior to patient entry.

4. Because of the teratogenic potential of the study medications, no patients who are
pregnant or lactating will be allowed. Patients of childbearing potential, who are
sexually active, must practice an effective method of birth control while
participating on this study, to avoid possible damage to the fetus . [e.g.
intrauterine device, double-barrier method (i.e., diaphragm, or a cervical cap) with
intravaginal spermicidal foam, cream or gel], or male partner sterilization
throughout the study].

5. Patients who are on hemodialysis

6. Proteinuria, in the absence of urinary infection, within 4 weeks prior to the
planned treatment date is a relative contraindication to receiving therapy for
patients with pheochromocytoma/paraganglioma. Patients with
pheochromocytoma/paraganglioma with any clinically significant proteinuria must have
a 24-hr urine protein determination. If proteinuria is confirmed as being above the
institutional upper limit of normal, the patient is ineligible for MIBG therapy.

7. Patients with active infections that meet grade 3-4 according to the current version
of the NCI CTCAE.

8. Patients with known MIBG-avid parenchymal brain metastases are not eligible.
(Patients with leptomeningeal or skull-based metastases are eligible.)