N2007-01: Ultratrace™ Iobenguane I 131 in Patients With Relapsed/Refractory High-Risk Neuroblastoma

OBJECTIVES:

Primary

- To establish the maximum tolerated dose of iodine I 131 metaiodobenzylguanidine
(^131I-MIBG) in patients with relapsed/refractory high-risk neuroblastoma.

Secondary

- To describe toxicity following treatment with ^131I-MIBG in patients with
relapsed/refractory high-risk neuroblastoma.

- To estimate radiation absorbed doses to measurable lesions and to a standard set of
normal organs following a 0.1 mCi/kg [3.7 MBq/kg] (minimum dose of 1.0 mCi [37 MBq] but
not to exceed 5.0 mCi [185 MBq]) intravenous administration of ^131I-MIBG in patients
with relapsed/refractory high-risk neuroblastoma.

- To describe, within the confines of a phase IIa trial, objective tumor response
following treatment with ^131I-MIBG in patients with relapsed/refractory high-risk
neuroblastoma.

- To explore dose-response following treatment with ^131I-MIBG in patients with
relapsed/refractory high-risk neuroblastoma.

- To explore quality of life assessment following treatment with ^131I-MIBG in patients
with relapsed/refractory high-risk neuroblastoma.

OUTLINE:

- Dosimetry: Patients receive a dosimetric dose of iodine I 131 metaiodobenzylguanidine
(^131I-MIBG) IV over 1-3 minutes. Patients then undergo 2 or 3 MIBG scans within 5 days
of the dosimetry dose to assess biodistribution and tumor uptake. Patients with normal
tumor uptake and biodistribution proceed to treatment.

- Treatment: Within 1-4 weeks of the dosimetric dose, patients with normal tumor uptake
and biodistribution receive a therapeutic dose of ^131I-MIBG IV over 1 hour on day 0 and
undergo MIBG scan on day 7. Patients then proceed to autologous stem cell infusion.

- Autologous stem cell infusion: Patients receive an infusion of autologous stem cells
from peripheral blood or bone marrow on day 14. Patients with an ANC of < 500/µl at any
point after autologous stem cell infusion receive filgrastim (G-CSF) IV or
subcutaneously once daily until ANC is > 2,000/µl.

Patients complete a quality of life questionnaire at baseline and then at day 60.

After completion of study treatment, patients are followed at day 60 and periodically
thereafter.

Inclusion Criteria:

- Patients must be at least one year and no more than 30 years of age when registered on
this study.

- Patients must have high risk neuroblastoma and either have tumor left after treatment
started at diagnosis or have had the tumor grow back (relapsed) after getting some
treatment

- Patients must an MIBG scan done and it must be positive for neuroblastoma.

- Patients must have a PBSC or bone marrow stem cell product available that meets study
criteria. If they don't already have stem cells frozen away then they must be able to
have a stem cell pheresis done to collect the necessary amount of stem cells for study
entry and these stem cells must meet study criteria.

- Patients must have adequate heart, lung, liver, kidney and bone marrow function.

Exclusion Criteria:

- They have had a stem cell transplant using another person as the stem cell donor. (You
can still be in the study if a previous transplant used your own stem cells)

- They have other medical problems that could get much worse if they had this treatment.

- They are on dialysis for badly working kidneys or have other kidney problems.

- They are pregnant or breast feeding.

- They have tumor in the brain or spinal cord that is seen on a CT or MRI scan one month
before starting treatment

- They had total body radiation or radiation to the entire belly.

- They have a known allergy to MIBG, iodine or SSKI.

- They can't cooperate with the special precautions that are needed during UltratraceTM
MIBG treatment or with other safety monitoring requirements of the study..