Background:
Neuroblastoma is a type of cancer that causes tumors in nerves. It affects mainly infants and toddlers, and it causes about 15 percent of cancer-related deaths in children.
Objective:
To test a new drug (rhIL-15), combined with 3 standard cancer drugs, in people with neuroblastoma.
Eligibility:
People aged 3 to 35 years with neuroblastoma that did not respond or returned after standard treatment.
Design:
Participants will be screened. They will have a physical exam with blood and urine tests. They will have imaging scans and tests of their heart and lungs. They will have a bone marrow biopsy: A sample of tissue and fluid from inside a bone will be removed with a large needle.
Participants will be treated in 21-day cycles. They may have up to 4 treatment cycles.
rhIL-15 is given through a needle into a vein over 5 to 7 days during the first week of each cycle. Participants will stay in the hospital while they are receiving the rhIL-15.
Starting in the second week of the second cycle, participants will receive other drugs for treating cancer. They will have no study treatments during the third week of each cycle.
Participants will visit the clinic at least 2 times a week throughout all 4 treatment cycles. They will have a physical exam and blood tests during these visits. Imaging scans, bone marrow biopsy, and other tests will be repeated at the end of cycles 2 and 4.
Participants will have a follow-up visit 6 months after treatment ends. This visit will include a physical exam with blood and urine tests.
Histologic diagnosis: Participants must have pathology-confirmed neuroblastoma (no time limit). Old reports and tissue blocks can be used if available. Confirmation of disease will be based on the review of pathology at the NIH any time before starting and is based on one of the following: (1) A confirmed pathological diagnosis made from tumor tissue by light microscopy (with or without immunohistology or electron microscopy), (2) the combination of bilateral bone marrow aspirate and trephine biopsy containing confirmed tumor cells (e.g., syncytia or immunocytologically positive clumps of cells) and increased levels of urinary catecholamine metabolites.
Active disease status: Participants must have relapsed and/or refractory disease after receiving frontline chemotherapy and at least one salvage treatment (can include dinutuximab, temozolomide, and/or irinotecan), with no alternative curative options.
Measurable tumors on magnetic resonance imaging (MRI) or computed tomography (CT) scan. Measurable is defined as >=10 mm in at least one dimension.
Either 123MIBG-avid lesion detected on 123MIBG scan with positive uptake at a minimum of one site or FDG-PET-avid lesion detected on FDG-PET scan with positive uptake at a minimum of one site. This site must represent disease recurrence after completion of therapy, progressive disease on therapy, or refractory disease during induction.
Presence of pericardial effusion.
Chronic immunosuppression (physiologic steroid supplementation is allowed but any chronic immunosuppressant like steroids or other modulators are not allowed)
Major surgery within 4 weeks prior to initiation of study therapy
Current/active human immunodeficiency virus (HIV) infection, as measured by seropositivity for HIV antibody.