| Eligibility |
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
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