Therapy for Children With Advanced Stage Neuroblastoma
Neuroblastoma
About this trial
This is an interventional treatment trial for Neuroblastoma focused on measuring Anti-GD2 monoclonal antibody, hu14.18K322A, High-risk neuroblastoma, Phase II, Allogeneic NK cells
Eligibility Criteria
PARTICIPANT Inclusion Criteria:
- Participants <19 years of age (eligible until 19th birthday).
Newly diagnosed, advanced stage, high-risk neuroblastoma defined as one of the following:
- Children < 1 year with International Neuroblastoma Staging System (INSS) stage 2a, 2b, 3, 4 or 4S disease AND MYCN amplification (>10 copies, or greater than four-fold increase in MYCN signal as compared to reference signal).
- INSS 2a or 2b disease AND MYCN amplification, regardless of age or additional biologic features
INSS stage 3 AND:
- MYCN amplification (>10 copies, or greater than four-fold increase in MYCN signal as compared to reference signal, regardless of age or additional biologic features
- Age > 18 months (> 547 days) with unfavorable pathology, regardless of MYCN status
INSS stage 4 and:
- MYCN amplification, regardless of age or additional biologic features
- Age > 18 months (> 547 days) regardless of biologic features
- Age 12 - 18 months (365 - 547 days) with any of the following three unfavorable biologic features (MYCN amplification, unfavorable pathology and/or DNA index =1) or any biologic feature that is indeterminant/unknown
- Children at least 365 days initially diagnosed with: INSS stage 1, 2, 4S who progressed to a stage 4 without interval chemotherapy.
- Histologic proof of neuroblastoma or positive bone marrow for tumor cells with increased urine catecholamines.
- Adequate renal and hepatic function (serum creatinine <3 x upper limit of normal for age, AST< 3 x upper limit of normal).
- No prior therapy, unless an emergency situation requires local tumor treatment (discuss with principal investigator).
- Written, informed consent according to institutional guidelines.
PARTICIPANT Exclusion Criteria:
- Any evidence, as judged by the investigator, of severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease).
- Pregnant or breast feeding (female of child-bearing potential).
- Children with INSS 4 disease, age <18 months with all 3 favorable biologic features (non-amplified MYCN, favorable pathology and DNA index >1).
DONOR Inclusion Criteria:
- Potential donor is a biologic parent
- Potential donor is at least 18 years of age.
Sites / Locations
- St. Jude Children's Research Hospital
Arms of the Study
Arm 1
Experimental
Treatment
Participants receive IV hu14.18K322A with each course of chemotherapy (cyclophosphamide, topotecan, cyclophosphamide, doxorubicin, vincristine, cisplatin, and etoposide). Mesna will be given prior to and after cyclophosphamide infusion. Peripheral blood stem cell harvest (PBSC) and surgical resection of primary tumor will be performed, if feasible. Intensification therapy includes busulfan, melphalan, and levetiracetam with peripheral blood stem cell transplantation. A course of hu14.18K322A with natural killer cell infusion will be given to consenting participants. Radiation therapy will follow PBSC transplant with the exception of any patient requiring emergent radiotherapy. MRD treatment includes hu14.18K322A, G-CSF, GM-CSF, interleukin-2 and isotretinoin. Cells for infusion are prepared using the CliniMACS System.