High-Dose 131I-MIBG Therapy Combined With Vincristine and Five Days of Irinotecan for Resistant/Relapsed Neuroblastoma

Inclusion Criteria

• Age: Patients must be >1 year and 50% marrow space). Patients are excluded if they have received whole abdominal radiation or TBI (total body irradiation).
• Stem Cell Transplant (SCT): Patients are eligible three months after autologous stem cell transplant. Patients status post-allogeneic stem cell transplant are excluded. Must meet adequate bone marrow function definition (see organ function requirements, below) post-myeloablative therapy.
• Prior 131I-MIBG therapy: Patients may have received prior MIBG therapy, though cumulative lifetime dose should not exceed 18 mCi/kg prior to study entry. Patients must not have received MIBG in combination with irinotecan. For patients previously treated with MIBG, at least 6 months must have elapsed since last MIBG therapy.
• Growth factor(s): All cytokines or hematopoietic growth factors must be discontinued a minimum of 7 days prior to the start date for irinotecan on this protocol.
• Prior irinotecan and vincristine therapy: are allowed, subject to recovery of adequate bone marrow function as specified in the protocol.
• Concomitant Therapy Restrictions: Patients must not be receiving any other anti-cancer agents or radiotherapy at the time of study entry or while on study. Enzyme-inducing anticonvulsants (phenobarbital, phenytoin, carbamazepine) must not be used as these may interfere with irinotecan metabolism. Non-enzyme inducing anticonvulsants (Keppra, etc.) can be used after discussion with study chair. The use of high dose dexamethasone and the use of aprepitant as antiemetics is not recommended due to effects on irinotecan metabolism.
• Hematologic function: a. ANC: > 750/uL (no hematopoietic growth factors within 7 days of the start date for irinotecan on this protocol) b. Platelet count: > 50,000/µl, transfusion independent (defined as no platelet transfusion for one week).

c. These criteria must be met by all patients, regardless of bone marrow involvement with tumor.

• Renal function: a. Glomerular Filtration Rate (GFR) or 12-24hr Creatinine Clearance >= 60 ml/min/1.73 m², OR b. Age-adjusted serum creatinine 5 and 10 and 15 years 1.5
• Liver function: a. Total bilirubin =55%) documented by either echocardiogram or radionuclide MUGA evaluation OR normal fractional shortening (>= 27%) documented by echocardiogram.
• Lung function: Normal lung function with no dyspnea at rest, exercise intolerance, pleural effusion or oxygen requirement.
• Reproductive function: All post-menarchal females must have a negative urine or serum beta-HCG. Males and females of reproductive age and childbearing potential must use effective contraception for the duration of their participation.
• Coexisting medical conditions: Patients with other ongoing serious medical issues must be approved by the study chair prior to registration.

Exclusion Criteria

• Pregnant or lactating.
• Patients status post-ALLOGENEIC stem cell transplant are NOT eligible.
• Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.
• Patients with disease of any major organ system that would compromise their ability to withstand therapy.
• Patients who are on hemodialysis.
• Patients with a documented allergy to 3rd generation cephalosporins.
• Patients must not have active diarrhea (defined as > Grade 2 per CTCAE v4 [ Grade 2 = increase of 4-6 stools/day over baseline] ).
• Patients with an active or uncontrolled infection, including C. difficile, of > grade 3 per CTCAE v4. Patients on prolonged antifungal therapy are eligible if they are culture and biopsy negative in suspected radiographic lesions and meet other organ function criteria.
• Patients and/or families who are physically and psychologically unable to cooperate with the radiation safety isolation.
• Patients who have received prior total body or whole abdominal radiation.
• Patients who have received prior 131I-MIBG therapy in combination with irinotecan.