Vaccine Therapy (GVAX), Nivolumab, and Ipilimumab for the Treatment of Relapsed or Refractory Neuroblastoma

Inclusion Criteria

• ELIGIBILITY CRITERIA FOR NEUROBLASTOMA CELL COLLECTION AND VACCINE MANUFACTURE:
• Patients with histologically confirmed neuroblastoma, who meet the Children’s Oncology Group (COG) high-risk group assignment criteria
• Lansky/Karnofsky performance status >= 50%
• Participants must have clinical indication for surgical resection of their neuroblastoma and undergo resection at Boston Children’s Hospital
• Ability to understand and/or the willingness of their parent or legally authorized representative to sign a written informed consent document
• ELIGIBILITY CRITERIA TO COMMENCE TO RECEIVE STUDY TREATMENT WITH IRRADIATED GM-CSF SECRETING AUTOLOGOUS TUMOR VACCINE, NIVOLUMAB, AND IPILIMUMAB:
• Histologically confirmed high-risk neuroblastoma based on COG assignment criteria
• Residual disease at the end of standard therapy or relapsed neuroblastoma in any disease state (including complete response [CR]) by clinical criteria (histologic confirmation of relapse or residual disease is not required)
• Age >= 1 year of age
• Lansky / Karnofsky performance status >= 50%
• Prior Therapy – Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimal duration from prior anti-cancer directed therapy prior to enrollment: * Myelosuppressive chemotherapy: At least 21 days after the last dose of myelosuppressive chemotherapy * Small molecule biologic therapy: At least 7 days following the last dose of a biologic agent * Monoclonal antibodies >= 7 days or 3 half-lives whichever is longer but no longer than 30 days (with recovery of any associated toxicities) * External beam irradiation: >= 14 days after small port radiation therapy (XRT), >= 12 weeks after large port radiation (>= 50% of the marrow space) including total body irradiation, craniospinal radiation, whole abdomen and whole lung radiation * 131I-Metaiodobenzylguanidine (MIBG) therapy >= 6 weeks * Autologous stem cell infusion following myeloablative therapy >= 6 weeks * Any other investigational agents >= 14 days
• Absolute neutrophil count (ANC) >= 500/uL
• Hemoglobin (Hgb) > 8 (may not be transfused)
• Platelet count >= 30,000 (may not be transfused)
• Total bilirubin =< 1.5 x upper limit of normal for age
• Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x upper limit of normal (135 U/L) * For the purpose of this study, the upper limit of normal (ULN) for ALT is 45 U/L
• A serum creatinine based on age/sex as follows: * Age: Maximum serum creatinine (mg/dL) * 1 to < 2 years: 0.6 (male and female) * 2 to < 6 years: 0.8 (male and female) * 6 to < 10 years: 1 (male and female) * 10 to < 13 years: 1.2 (male and female) * 13 to < 16 years: 1.5 (male), 1.4 (female) * >= 16 years: 1.7 (male), 1.4 (female) OR creatinine clearance >= 60 mL/min/1.73 m^2 for participants with creatinine levels greater than the above age/sex maximum allowed values
• No evidence of dyspnea at rest
• No exercise intolerance due to pulmonary insufficiency
• Pulse oximetry > 92% while breathing room air
• Serum lipase =< ULN at baseline
• No >= grade 2 non-hematologic toxicity
• Absolute eosinophil count =< 5000/ul
• Negative beta-human chorionic gonadotropin (B-HCG) pregnancy test in females of childbearing potential. Must be drawn or repeated within 24 hours prior to initial administration of study drugs
• Women of childbearing potential (WOCBP) receiving nivolumab will agree to adhere to contraception for a period of 5 months after the last dose of nivolumab. Men receiving nivolumab and who are sexually active with WOCBP will agree to adhere to contraception for a period of 7 months after the last dose of nivolumab

Exclusion Criteria

• Participants who are receiving any other investigational agents
• No systemic corticosteroid therapy, other than replacement therapy for adrenal insufficiency or transfusion premedication. Participants who are receiving or have received lympholytic steroid (>= 40 mg/m^2 prednisone equivalent) therapy within 4 weeks of first anticipated vaccine administration are excluded, because high-dose steroid therapy is expected to significantly limit the ability of the immune system to respond to GVAX vaccination
• Participants with known parenchymal brain metastases
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to GM-CSF or dimethyl sulfoxide (DMSO)
• Participants with any form of primary immunodeficiency
• Females who are pregnant are excluded from this study because GVAX is an investigational biologic with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with GVAX, breastfeeding should be discontinued if the mother is treated with GVAX
• Uncontrolled intercurrent illness or serious uncontrolled medical disorder including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia and/or pronounced disturbances of the electrical conduction system of the heart or psychiatric illness/social situations that would limit compliance with study requirements
• Known human immunodeficiency virus (HIV)-positive participants on combination antiretroviral therapy are ineligible because of the effect of GVAX vaccination on the disease course is unknown and because the underlying disease is expected to limit the ability of the immune system to respond to GVAX vaccination
• Clinically relevant known active infection including active hepatitis B or C or any other concurrent disease which in the judgment of the investigator would make the subject inappropriate for enrollment on this study
• History of a malignancy other than neuroblastoma with exception of the following circumstances: * Patients with a history of malignancy who have been adequately treated and have been disease-free for at least 2 years are not excluded * Patients with adequately treated active non-invasive cancers (such as non-melanomatous skin cancer or in-situ bladder, cervical and breast cancers) are not excluded
• Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 or anti-CTLA4 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. OX-40, CD137)
• Has received prior live cellular therapy (natural killer [NK] cell, chimeric antigen receptor T-cell [CAR-T cell])
• Has active autoimmune disease that has required systemic treatment in the past 12 months, or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy are exceptions. Intermittent use of bronchodilators or local steroid injections are not excluded. Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Autoimmune diagnoses not listed must be approved by the protocol chair
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis