An Open Label, Expanded Access Protocol Using 131I-Metaiodobenzylguanidine (131I-MIBG)Therapy In Patients With Refractory Neuroblastoma, Pheochromocytoma, Or Paraganglioma
- Children’s Medical Center (Dallas, Plano, Southlake)
Tanya Watt, M.D.
This is an expanded access protocol which provides a mechanism to deliver this therapy when clinically indicated, but also to provide a mechanism to continue to collect safety and efficacy data that will be provided to the Food and Drug administration(FDa) that will ultimately be used for FDa approval of 131i-MiBG targeted radiotherapy.
The 131i-MiBG will be given through an iV line over 1.5 - 2 hours. Post-treatment evaluation will be performed 5-9 weeks (35-63 days) post treatment. Participants will be followed closely by the study doctor for the entire time they are receiving 131i-MiBG therapy and for up to 2 years following treatment .
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. 4.1.2 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.
* 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 number may be met by combining different types of stem cell products as listed below (ie: purged + unpurged PBSC).
* The minimum dose for bone marrow is 1.0 x 108 mononuclear cells/kg (optimum > 2.0 x 108 mononuclear cells/kg).
Allogeneic Stem cell source: The majority of patients on this protocol will have an autologous PBSC product available. Where a syngeneic donor is available, this donor may also be utilized. In the case of a patient who has received a prior allogeneic transplant, if the donor is available, allogeneic stem cells may be utilized. For these patients, 3 criteria must be met: 1) There must be no evidence of graft vs. host disease (GVHD), 2) The patient must be on no medication for GVHD treatment or prophylaxis and 3) There must be full donor chimerism (>95% donor on peripheral blood chimerism testing). The only acceptable allogeneic product is CD34-selected PBSC (which will minimize the risk of GVHD). If no stem cells are available, then the dose of 131I-MIBG should be <12 mCi/kg. 4.1.5 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:
* At least 2 weeks should have elapsed since any anti-tumor therapy and the patient must meet hematologic criteria below.
* 3 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
* Cytokine therapy (e.g. G-CSF, GM-CSF, IL-6, erythropoietin) must be discontinued a minimum of 24 hours prior to 131I-MIBG therapy.
* Minimum of six weeks from previous 131I-MIBG therapy.
* For patients previously treated with MIBG and with remaining stored stem cells that meet the criteria stated in 4.1.4, treatment on this protocol must not exceed a lifetime cumulative injected activity of 54 mCi/kg.
* For patients previously treated with MIBG and without remaining stored stem cells that meet the criteria listed in 4.1.4 AND for patients with pheochromocytoma/paraganglioma, retreatment on this protocol must not exceed a lifetime cumulative injected activity of 36 mCi/kg.
* For patients who received a stem cell infusion for a previous 131I-MIBG therapy but do NOT have remaining stored stem cells:
o 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
o If the stem cell reinfusion was given based upon the development of profound cytopenias, the patient is NOT eligible for re-treatment.
Liver function: Bilirubin <= 2x upper limit of normal; AST/ALT <= 10x upper limit of normal
Kidney function One of the following must be met: Serum Creatinine <= 2x upper limit of normal OR 24-hr creatinine clearance OR
Normal lung function as manifested by no dyspnea at rest or exercise intolerance, no oxygen requirement 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/[MICRO-SYMBOL]L; Platelets >= 50,000/[MICRO-SYMBOL]L 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.
No clinically significant cardiac dysfunction
Signed informed consent/assent: The patient and/or the patient[Single Quote]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.