Expanded Access Protocol Using I131-MIBG

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2012 by Jubilant DraxImage Inc..
Recruitment status was  Available
Sponsor:
Information provided by (Responsible Party):
Jubilant DraxImage Inc.
ClinicalTrials.gov Identifier:
NCT01590680
First received: May 1, 2012
Last updated: May 2, 2012
Last verified: April 2012

May 1, 2012
May 2, 2012
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Complete list of historical versions of study NCT01590680 on ClinicalTrials.gov Archive Site
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Expanded Access Protocol Using I131-MIBG
An Open Label, Expanded Access Protocol Using 131I-metaiodobenzylguanidine (131I-MIBG)Therapy in Patients With Refractory Neuroblastoma, Pheochromocytoma, or Paraganglioma

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.

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.

Expanded Access
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  • 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 Names:
  • I-131 Iobenguane
  • I-131 meta-iodobenzylguanidine
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
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Inclusion Criteria:

  • 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 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 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).
  • 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.

    • The minimum quantity for purged or unpurged peripheral blood stem cells (PBSC) is 1.5 x 106 viable CD34+ cells/kg (recommended 2 x 106 viable CD34+ cells/kg).
    • The minimum dose for bone marrow is 1.0 x 108 mononuclear cells/kg (optimum > 2.0 x 108 mononuclear cells/kg).
  • 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: 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 (e.g. G-CSF, GM-CSF, IL-6, erythropoietin) must be discontinued a minimum of 24 hours prior to 131I-MIBG therapy.
  • Liver function: Bilirubin ≤ 2x upper limit of normal; AST/ALT ≤ 10x upper limit of normal
  • Kidney function: 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.)
  • Hematologic Criteria: 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. Any significant organ impairment should be discussed with the Principal Investigator prior to patient entry.
  • Because of the teratogenic potential of the study medications, 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 v3.0.
  • Patients with known MIBG-avid parenchymal brain metastases are not eligible. (Patients with leptomeningeal or skull-based metastases are eligible.)
Both
12 Months and older
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Contact: Brian Weiss, M.D. 513-636-9863 brian.weiss@cchmc.org
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NCT01590680
JDI2007-01
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Jubilant DraxImage Inc.
Jubilant DraxImage Inc.
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Principal Investigator: Weiss Brian, M.D. Cincinnati Children's Hospital (brian.weiss@cchmc.org)
Principal Investigator: Suzanne Shusterman, M.D. Dana-Farber Cancer Center Boston Children's Hospital
Principal Investigator: Greg Yanik, M.D. C.D. Mott's Children's Hospital University of Michigan, Ann Arbor (gyanik@umich.edu)
Principal Investigator: Haydar Frangoul, M.D. Monroe Caroll Children's Hospital at Vanderbilt
Principal Investigator: Michael Armstrong, M.D., Ph.D. Duke University
Principal Investigator: Julie Park, M.D. Seattle Children's Hospital
Principal Investigator: Meaghan Granger, M.D. Cook Children's Health Care System
Principal Investigator: Araz Marachelian, M.D. Children's Hospital Los Angeles
Jubilant DraxImage Inc.
April 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP