131I-omburtamab for the Treatment of Central Nervous System/Leptomeningeal Neoplasms in Children and Young Adults

Inclusion Criteria:

• Patients must have a histologically confirmed diagnosis of an embryonal malignancy (including but not limited to neuroblastoma, medulloblastoma, rhabdoid tumors,pineoblastoma, retinoblastoma, PNET, rhabdomyosarcoma, Ewing's sarcoma, Wilm'stumor, hepatoblastoma) other non-embryonal tumors must have histologic confirmationof B7-H3 reactivity.

• Patients must have a diagnosis of CNS/ leptomeningeal disease which has been treatedwith conventional therapies or for which no conventional therapy exists or arecurrent brain tumor with a predilection for leptomeningeal dissemination (i.e.PNET, rhabdoid tumor).

• Chemotherapy:

°Patients must have received their last dose of myelosuppressive anticancer therapyat least 21 days (3 weeks) prior to receiving treatment dose(s).

• Biologic or investigational agent (anti-neoplastic):

• Patients who are currently on biological (small molecule inhibitors such as ALKinhibitors, ROS inhibitors or MEK inhibitors etc.) or investigational agentsthat are considered non-myelosuppressive can continue treatment but should haverecovered from any acute toxicity potentially related to the agent.

• Patients may be treated if they received one prior treatment dose with 131I-omburtamab

• Monoclonal antibody treatment and agents with known prolonged half-lives:

• Patients must have recovered from any acute toxicity potentially related to theagent and received their last dose of the agent ≥ 21 days prior to enrollment.

• Monoclonal antibody treatment and agents with known prolonged half-lives:Patient must have recovered from any acute toxicity potentially related to theagent and received their last dose of the agent ≥ 28 days prior to receivingtreatment dose(s).

• Neurologic Status:

• Patients with neurological deficits should have deficits that are stable for aminimum of 1 week prior to enrollment.

• Patients with seizure disorders may be enrolled if seizures are controlled.

• Performance Status:

°Karnofsky Performance Scale (KPS for > 16 years of age) or Lansky Performance Score (LPS for ≤ 16 years of age) assessed within 2 weeks prior to study enrollment mustbe ≥ 50%. Patients who are unable to walk because of neurologic deficits, but whoare up in a wheelchair, will be considered ambulatory for the purpose of assessingthe performance score.

• Adequate bone marrow function defined as:

• Peripheral absolute neutrophil count (ANC) ≥ 0.5x 10^9/ L (must not havereceived G-CSF within the 7 days prior to enrollment or pegfilgrastim withinthe 14 days prior to enrollment)

• Platelet count ≥ 50 x 10^9/ L (unsupported, defined as no platelet transfusionwithin 7 days prior to study enrollment)

• Intraventricular Access Device °Protocol treatment with radioimmunotherapy (131I-omburtumab) will require the presence of an appropriate intraventricularaccess device (e.g.,programmable ventriculoperitoneal [VP] shunt or Ommayareservoir). Patients are not required to have an existing programmable VP shunt orOmmaya at the time of study enrollment but must be willing and able to undergo asurgical procedure to have one placed prior to Radioimmunotherapy.

Note: Patients with an existing intraventricular VP shunt without a programmable component must be willing and able to undergo modification of the shunt before treatment with 131I-omburtumab.

• Both pediatric and adult patients of any age are eligible.

• Patients may have active malignancy outside the central nervous system.

• Patients may be on standing steroids, as long as the dosage is either stable ordecreasing for at least week prior to enrollment

• Signed informed consent and assent when appropriate indicating awareness of theinvestigational nature of this study.

Exclusion Criteria:

• Patients with obstructive or symptomatic communicating hydrocephalus

• Patients with an uncontrolled life-threatening infection

• Patients who are pregnant: negative pregnancy test is required for all women ofchildbearing age, and appropriate contraception is required during the study period.

• Patients who have received cranial or spinal irradiation less than 3 weeks prior tofirst dose