Biological Therapy, Sargramostim, and Isotretinoin in Treating Patients With Relapsed or Refractory Neuroblastoma

Inclusion Criteria

• The target tumor is limited to neuroblastoma; patients must have had histologic verification of neuroblastoma and/or demonstration of tumor cells in the bone marrow with increased urinary catecholamines at the time of initial diagnosis
• Patients must have resistant/refractory or recurrent neuroblastoma
• Tumor imaging and bone marrow evaluation for histologic analysis of marrow tumor cell quantity must be obtained within 3 weeks (21 days) prior to enrollment onto study and patients must have one of the following:
• Measurable tumor on magnetic resonance imaging (MRI), computed tomography (CT) scan, or x-ray defined as minimum of 20 mm in at least one dimension; measurable is defined as minimum of 20 mm in at least one dimension; for patients who are in first response (i.e., those patients with persistent sites of tumor after frontline therapy, but who have never relapsed), a biopsy of a lesion or bone marrow must demonstrate viable neuroblastoma following completion of therapy; if the lesion was irradiated, the biopsy must be done at least 4 weeks after radiation is completed
• Meta iodo benzyl guanidine I 123 (MIBG) scan with positive uptake at minimum of one site; for patients in first response, a biopsy of site must demonstrate viable tumor; if lesion was radiated, biopsy must be done at least 4 weeks after radiation completed
• Bone marrow with tumor cells seen on routine morphology (not by neuron specific enolase (NSE) staining only) of bilateral aspirate and/or biopsy on one bone marrow sample
• Patients must have a performance status of 0, 1 or 2; use Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients = = 2 wks for local palliative XRT (small port); >= 6 months must have elapsed if prior craniospinal XRT or if >= 50% radiation of pelvis; >= 6 weeks must have elapsed if other substantial bone marrow (BM) radiation
• Autologous stem cell transplant (ASCT): Patients are eligible > 56 days after autologous stem cell infusion following myeloablative therapy; patients receiving an autologous stem cell infusion to support non-myeloablative therapy (including 131I-MIBG given as a single agent) are eligible at any time as long as they meet the hematologic and other organ function criteria for eligibility; patients who have received an allogenic stem cell transplant are excluded
• radioactive iodine (131 I) MIBG therapy: Patients are eligible > 6 weeks after therapeutic 131I-MIBG
• Study specific limitations on prior therapy: Subjects who have previously received in vivo anti-GD2 monoclonal antibodies for biologic therapy or for tumor imaging, are eligible unless they have had progressive disease or a severe allergic reaction while receiving prior anti-disialoganglioside (GD2) therapy; subjects who have received autologous marrow infusions or autologous stem cell infusions using monoclonal antibody linked to beads to purge specimens, but no other form of anti-GD2 monoclonal antibody, are eligible
• Growth factor(s): Must not have received within 1 week of entry onto this study
• Steroids: Patients who require or are likely to require corticosteroid or other immunosuppressive drugs for intercurrent disease (any other significant medical problem related to or independent from the neuroblastoma or its treatment) while tentatively scheduled to be receiving treatment on this study are ineligible; the only exception is for patients known to require 2 mg/kg or less of hydrocortisone (or an equivalent dose of an alternative corticosteroid) as premedication for blood product transfusion in order to avoid allergic transfusion reactions
• Peripheral absolute phagocyte count (APC=neutrophils + monocytes) >= 1000/uL
• Platelet count ≥ 20,000/μL*
• Hemoglobin ≥ 8 g/dL*
• Transfusions are permitted to meet these platelet and hemoglobin criteria, if the patient is known to have a history of bone marrow involvement with tumor; patients with platelet counts = 70 mL/min OR serum creatinine based o