N2004-06: Irinotecan and Vincristine With 131I-MIBG Therapy for Resistant/Relapsed High-Risk Neuroblastoma

DISEASE CHARACTERISTICS:

Inclusion criteria:

   - Must have a diagnosis of neuroblastoma by histologic verification and/or demonstration
   of tumor cells in the bone marrow with increased urinary catecholamines

   - Must have high-risk neuroblastoma AND meets at least one of the following criteria:

      - Recurrent or progressive disease at any time

         - Biopsy not required, even if there is partial response to intervening
         therapy

      - Refractory disease (i.e., less than a partial response to frontline therapy,
      including a minimum of 4 courses of chemotherapy)

         - Biopsy not required

         - If the patient has not had previous myeloablative therapy, preference will
         be given to NANT-2001-02 (iodine I 131 metaiodobenzylguanidine [^131I-MIBG]
         + CEM)

      - Persistent disease after at least a partial response to frontline therapy (i.e.,
      patient still has residual disease by MIBG scan, CT/MRI scan, or bone marrow)

         - Biopsy required (bone marrow biopsy included) of at least one residual site
         demonstrating viable neuroblastoma

         - If the patient has not had previous myeloablative therapy, preference will
         be given to NANT-2001-02 (^131I-MIBG + CEM)

   - Must have evidence of MIBG uptake into tumor at ≥ 1 site within 4 weeks prior to study
   entry and subsequent to any intervening therapy

   - Must have autologous hematopoietic stem cell product available and it must be free of
   tumor cell contamination (0 tumor cells /1,000,000 nucleated cells), cryopreserved,
   and available for re-infusion after ^131I-MIBG treatment, if immunocytology has been
   performed on the stem cell product

      - If immunocytology has not been performed on the stem cell product, then bilateral
      bone marrow aspirates and biopsies must have been negative by morphology within 4
      weeks before or after the stem cell collection

      - If the patient had no bone marrow disease documented at diagnosis or at any time
      prior to peripheral blood stem cell (PBSC) harvest then the criteria for
      bilateral bone marrow aspirates/biopsies is waived

      - The minimum dose is as follows:

         - Purged PBSC 2.0 x 10^6 viable CD34+ cells/kg

            - Immuno-magnetically purged cells are permitted

         - Unpurged PBSC 2 x 10^6 CD34+ cells/kg (minimum is same for PBSC from
         identical twin)

      - Cells from identical twins are permitted

         - Other allogeneic cells are not allowed

      - CD34+ selected cells are not permitted

PATIENT CHARACTERISTICS:

Inclusion criteria:

   - Lansky or Karnofsky performance status ≥ 50%

   - Life expectancy ≥ 6 weeks

   - Hemoglobin ≥ 8 g/dL (transfusion allowed)

   - ANC ≥ 750/μL (no hematopoietic growth factors within 7 days of starting irinotecan
   hydrochloride)

   - Platelet count ≥ 50,000/μL (transfusion independent, defined as no platelet
   transfusion for 2 weeks)

   - Glomerular filtration rate (GFR) or creatinine clearance ≥ 60 mL/min OR age-adjusted
   serum creatinine ≤ 1.5 x normal, according to the following:

      - 0.8 mg/dL (≤ 5 years of age)

      - 1.0 mg/dL (6 to 10 years of age)

      - 1.2 mg/dL (11 to 15 years of age)

      - 1.5 mg/dL (≥ 16 years of age)

   - Total bilirubin ≤ 1.5 x normal for age

   - ALT and AST < 3 x normal for age

   - All post-menarchal females must have a negative beta-HCG

   - Males and females of reproductive age and childbearing potential must use effective
   contraception for the duration of study participation

   - Ejection fraction ≥ 55% by echocardiogram or radionuclide MUGA OR fractional
   shortening ≥ 27% by echocardiogram

   - Normal lung function

   - Patients with other ongoing serious medical issues must be approved by the study chair
   prior to study registration

Exclusion criteria:

   - Pregnancy or breast feeding

   - Dyspnea at rest, exercise intolerance, pleural effusion, or oxygen requirement

   - Disease of any major organ system that would compromise the patient's ability to
   withstand therapy

   - Documented allergy to third generation cephalosporins

   - Active diarrhea (defined as ≥ grade 2 per CTCAE v3)

   - Active or uncontrolled infection, including C. difficile

      - Patients on prolonged antifungal therapy are eligible if suspected radiographic
      lesions are culture and biopsy negative and patient meets other organ function
      criteria

   - Patients and/or families who are physically and psychologically unable to cooperate
   with the radiation safety isolation

   - Patient weight that would require exceeding a maximum total allowable dose of
   ^131I-MIBG (per institutional guidelines)

   - Patients who, in the opinion of the investigator, may not be able to comply with the
   safety monitoring requirements of the study

PRIOR CONCURRENT THERAPY:

Inclusion criteria:

   - Patients must have fully recovered from the acute toxic effects of all prior
   chemotherapy, immunotherapy, or radiotherapy before study entry

   - At least 3 weeks since prior myelosuppressive or biologic therapy

   - At least 2 weeks since prior radiation therapy

      - Radiation therapy should not be given to the only site of measurable or evaluable
      disease

   - At least 3 months since prior large field radiation therapy (i.e., craniospinal
   radiation therapy, total lung radiation therapy, or radiation therapy to > 50% of
   marrow space)

   - At least 3 months since prior autologous stem cell transplantation

      - Must meet adequate bone marrow function postmyeloablative therapy

   - At least 7 days since prior cytokines or hematopoietic growth factors

   - Prior irinotecan hydrochloride and vincristine therapy allowed provided the patient
   recovered to adequate bone marrow function as specified in the protocol

Exclusion criteria:

   - Prior ^131I-MIBG

   - Prior external beam radiation therapy to the liver or kidneys

   - Prior allogeneic stem cell transplantation

   - Prior whole abdominal radiation therapy, total-body irradiation, or local radiation
   therapy that includes any of the following:

      - 1,200 cGy to more than 33% of both kidneys (patient must have at least one kidney
      that has not exceeded the dose/volume of radiation listed)

      - 1,800 cGy to more than 30% of liver and/or 900 cGy to more than 50% of liver

   - Other concurrent cancer chemotherapy or immunomodulating agents (including steroids)

      - Steroids may be used in the prevention and treatment of transfusion/infusion
      reactions and for the treatment of edema associated with CNS lesions

   - Concurrent palliative radiotherapy to localized painful lesions

   - Concurrent aprepitant (Emend)

   - Concurrent ketoconazole or St. John's wort

   - Medications that interfere with MIBG uptake during the week prior to or after MIBG
   therapy

   - Concurrent enzyme-inducing anticonvulsants (e.g., phenobarbital, phenytoin, or
   carbamazepine)

      - Nonenzyme-inducing anticonvulsants (e.g., Keppra) may be allowed

   - Concurrent hemodialysis

   - Any other concurrent anticancer agents or radiation therapy