Official Title
An Open Label, Expanded Access Protocol Using 131I-metaiodobenzylguanidine (131I-MIBG) Therapy in Patients With Refractory Neuroblastoma, Pheochromocytoma, or Paraganglioma (Not Eligible for Approved Treatment)
Brief Summary

Protocol JDI2007-01 is an Expanded Access Protocol with therapeutic 131I-MIBG forpatients with neuroblastoma or pheochromocytoma / paraganglioma, who otherwise do notqualify for available treatments, or where approved treatment is not commerciallyavailable.

Detailed Description

Primary Objectives:

- To provide 131I-MIBG for compassionate use in patients with neuroblastoma, who
otherwise do not qualify for inclusion or cannot participate in the sponsor's
pivotal Phase II, FDA-approved, clinical trial.

- To provide 131I-MIBG for compassionate use in patients with neuroblastoma in the
absence of a commercially available FDA approved product for the indication.

- Provide palliative therapy with 131I-MIBG for patients with advanced neuroblastoma.

- To provide alternative therapeutic 131I-MIBG options for patients with
pheochromocytoma / paraganglioma, not qualifying for FDA-approved MIBG treatment.

- To provide alternative therapeutic 131I-MIBG options for patients with
pheochromocytoma / paraganglioma, in the absence of a commercially available
FDA-approved product for that indication.

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

Patients will receive a therapeutic dose at the investigator's discretion (5-18 mCi/kg).
However, a dose of 12 mCi/kg or higher requires stored stem cells. Patients may be
eligible for additional 131I-MIBG treatments (up to a cumulative total of 3 treatments)
if they meet certain criteria.

Treatments with 131I-MIBG must be separated by a minimum of six weeks from previous
131I-MIBG therapy. Post-treatment evaluation will be performed 5-9 weeks (35-63 days)
post treatment, and patients will be followed every 6 months until 2 years from therapy.
All patients will have toxicity monitoring for 2 years following 131I-MIBG therapy, or
until going off study.

Available
Neuroblastoma
Pheochromocytoma
Paraganglioma

Radiation: I-131 MIBG

The therapeutic dose (5-18 mCi/kg at investigator's discretion; any dose ≥12 mCi/kg
requires stored stem cells) will be diluted in normal saline, and will be infused
intravenously over 90-120 minutes.
Other Name: I-131 Iobenguane,I-131 meta-iodobenzylguanidine

Eligibility Criteria

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.)

Eligibility Gender
All
Eligibility Age
Minimum: 12 Months ~ Maximum: N/A
Countries
United States
Locations

Children's Hospital Los Angeles
Los Angeles, California, United States

Children's Hospital Colorado
Aurora, Colorado, United States

Children's Healthcare of Atlanta
Atlanta, Georgia, United States

University of Chicago Medical Center
Chicago, Illinois, United States

Dana-Farber Cancer Institute
Boston, Massachusetts, United States

Michigan Medicine, University of Michigan
Ann Arbor, Michigan, United States

Washington University School of Medicine
Saint Louis, Missouri, United States

North Carolina Children's Hospital
Chapel Hill, North Carolina, United States

Carolinas Medical Center/ Levine Children's Hospital
Charlotte, North Carolina, United States

Duke University Medical Center
Durham, North Carolina, United States

Cincinnati Children's Hospital
Cincinnati, Ohio, United States

The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States

UPMC Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States

Monroe Carell Jr. Children's Hospital at Vanderbilt
Nashville, Tennessee, United States

Children's Medical Center Dallas
Dallas, Texas, United States

Cook Children's Medical Center
Fort Worth, Texas, United States

Baylor College of Medicine, Texas Children's Hospital
Houston, Texas, United States

Seattle Children's Hospital
Seattle, Washington, United States

University of Wisconsin Hospital and Clinics, American Family Children's Hospital
Madison, Wisconsin, United States

Contacts

Melda Dolan, MD
+1-215-930-4550
meldadolan@jubl.com

Chinmay Bhavsar
+1-562-409-5541
chinmay.bhavsar@jubl.com

Jubilant DraxImage Inc.
NCT Number
MeSH Terms
Neuroblastoma
Pheochromocytoma
Paraganglioma
3-Iodobenzylguanidine