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