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An Open Label, Expanded Access Protocol Using 131I-METAIODOBENZYLGUANIDINE (131I-MIBG) Therapy in Patients With Refractory Neuroblastoma, Pheochromocytoma, or Paraganglioma

12 Months
Open (Enrolling)
Neuroblastoma, Pheochromocytoma, Paraganglioma

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Trial Information

An Open Label, Expanded Access Protocol Using 131I-METAIODOBENZYLGUANIDINE (131I-MIBG) Therapy in Patients With Refractory Neuroblastoma, Pheochromocytoma, or Paraganglioma

Neuroblastoma, pheochromocytoma, and paraganglioma remain fatal diseases for a large
percentage of patients, especially those with high-risk disease features who become
resistant to conventional therapy. 131I-metaiodobenzylguanidine (131I-MIBG) is a
norepinephrine analog that concentrates in adrenergic tissue and has been shown to be
sensitive and specific for detecting localized and metastatic neuroblastoma,
pheochromocytoma, and paraganglioma. More importantly, experience of many institutions has
proven that this agent used as a targeted radiotherapeutic has significant anti-tumor
activity against refractory neuroblastoma 1-7 as well as pheochromocytoma and paraganglioma.
Children's Hospital of Philadelphia, UCSF, and the University of Michigan have just
completed a large Phase 2 study of 131I-MIBG given in doses of 10-18 mCi/kg with stem cell
rescue, if necessary, and have shown that this agent is safe and effective palliative
therapy for refractory or relapsed neuroblastoma patients. In addition, there is growing
evidence that low-dose (5-10 mCi/kg) submyeloablative MIBG therapy is both safe and
effective for disease palliation. This protocol therefore provides a mechanism to deliver
this therapy when clinically indicated.

Primary Objectives:

- Provide palliative therapy with 131I-MIBG for patients with advanced neuroblastoma,
pheochromocytoma, or paraganglioma.

- Gain more information about acute and late toxicity of 131I-MIBG therapy for patients
with refractory neuroblastoma, pheochromocytoma, or paraganglioma.

Inclusion Criteria:

- Diagnosis: Refractory/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 not amenable to curative surgery

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

- Disease status: Failure to respond to standard therapy (usually combination
chemotherapy with/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 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 initial response to MIBG therapy (at [or around] the day 35-63
post-MIBG therapy evaluation).

- 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.

- The minimum quantity for purged or unpurged peripheral blood stem cells (PBSC)
is 1.5 x 10e6 viable CD34+ cells/kg (recommended 2 x 10e6 viable CD34+

- The minimum dose for bone marrow is 1.0 x 10e8 mononuclear cells/kg (optimum >
2.0 x 10e8 mononuclear cells/kg).

- Prior Therapy: Patients may enter this study with/without re-induction therapy for
recurrent tumor. Patients must have fully recovered from the toxic effects of any
prior therapy, meeting the following criteria: At least 2 weeks should have elapsed
since any anti-tumor therapy and the patient must meet hematologic criteria below.
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
(spot irradiation to skull-based metastases is NOT considered craniospinal radiation
for the purposes of this study. Cytokine therapy must be discontinued a minimum of 24
hours prior to 131I-MIBG therapy.

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

- Serum Creatinine ≤ 2x upper limit of normal OR 24-hr creatinine clearance OR GFR ≥ 60
ml/min/1.73m2(For example, a patient would meet this criteria if GFR < 60
ml/min/1.73m2 but serum creatinine ≤ 2x upper limit of normal.)

- ANC ≥ 750/µL; Platelets ≥ 50,000/µL 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. Hemoglobin must be ≥
10 gm/dL (transfusion allowed) regardless of stored stem cell availability.

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

- No clinically significant cardiac dysfunction

- Signed informed consent/assent: The patient and/or the patient's legally authorized
guardian must acknowledge in writing that consent/assent to become a study subject
has been obtained, in accordance with institutional policies approved by the U.S.
Department of Health and Human Services.

Exclusion Criteria:

- Patients with disease of any major organ system that would compromise their ability
to withstand therapy. Significant organ impairment should be discussed with the
Principal Investigator prior to patient entry.

- 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. Abstinence is an effective method
of birth control.

- Patients who are on hemodialysis

- 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
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.

- Patients with active infections that meet grade 3-4 according to the NCI CTCAE v4.0.

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

Type of Study:

Expanded Access

Study Design:


Principal Investigator

Brian Weiss, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Children's Hospital Medical Center, Cincinnati


United States: Food and Drug Administration

Study ID:

MIBG Expanded Access (NDP)



Start Date:

Completion Date:

Related Keywords:

  • Neuroblastoma
  • Pheochromocytoma
  • Paraganglioma
  • Neuroblastoma
  • Paraganglioma
  • Pheochromocytoma



Cincinnati Children's Hospital Medical CenterCincinnati, Ohio  45229-3039