The purpose of the study is to explore the combination of a bivalent vaccine, a sugar called beta-glucan (β-glucan), and a protein called granulocyte-macrophage colony stimulating factor (GM-CSF) as an effective treatment for people with high-risk neuroblastoma that is in complete remission. The combination may be effective because the different parts of the treatment work to strengthen the immune system's response against cancer cells in different ways.

Inclusion Criteria:

• Diagnosis of NB as defined by international criteria, i.e., histopathology (confirmed by the MSK Department of Pathology) or BM metastases plus high urine catecholamine levels or positivity in MIBG scan

• HR-NB as defined by risk-related treatment guidelines and international criteria,i.e., metastatic/non-localized disease with MYCN amplification (any age), MYCN-non-amplified metastatic disease >18 months old, MYCNamplified localized disease (any age), or disease resistant to standard chemotherapy.

• HR-NB (as defined above) and in 1) first CR at ≥ 6 months from initiation of immunotherapy using anti-GD2 antibody, or 2) second or subsequent CR (achieved after treatment for PD). CR is defined according to the International Neuroblastoma Response Criteria.Patients with positive MIBG scan but negative FDG-PET scan, and CR in BM, are eligible.

• Patients with grade 3 toxicities or less using the Common Toxicity Criteria (Version 5.0) developed by the National Cancer Institute of the USA (CTCAE v5.0) related to hematologic, cardiac, neurological, pulmonary, renal, hepatic or gastrointestinal function as determined by blood tests or physical exam.

• Hematologic Function

  • Absolute neutrophil count (ANC) ≥ 500/mcl
  • Absolute lymphocyte count ≥ 500/mcl
  • Hemaglobin (Hgb) ≥ 8 g/dL
  • Platelet count ≥ 50,000 mm^3

• Renal Function o Serum creatinine ≤ 3.0 x ULN

or

• eGFR >60 mL/min/1.73 m^2

  - Hepatic Function

• Serum bilirubin ≤ 3.0 × ULN

• Aspartate transaminase (AST) ≤ 5.0 × ULN

• Alanine aminotransferase (ALT) ≤ 5.0 × ULN

  • Prior treatment with other immunotherapy, including mAbs or vaccine, is allowed but must be completed ≥ 21 days before the 1st vaccination.

Note: Prior treatment with an investigational therapy must be completed ≥ 28 days before the 1st vaccination.

• ≥ 21 and ≤ 180 days between completion of systemic therapy and 1st vaccination.
• Patients have recovered from any toxicities grade 3 or higher caused by prior therapies.
• Patients previously enrolled on this trial are eligible for repeat enrollment if they did not complete all vaccine injections during the first time on protocol but they will be assigned to Group 3 and will not be included in the primary biostatistical analyses.
• A negative pregnancy test is required for patients w ith child-bearing capability.
• Signed informed consent indicating awareness of the investigational nature of this program.

Exclusion Criteria:

• Patients w ith significant (grade >4) hematologic, cardiac, neurological, pulmonary, renal, hepatic or gastrointestinal function as determined by blood tests or physical exam, using the Common Toxicity Criteria (Version 5.0) developed by the National Cancer Institute of the USA (CTCAE v5.0)
• History of allergy to KLH, QS-21, OPT-821, or glucan.
• Active life-threatening infection requiring systemic therapy.
• Inability to comply with protocol requirements.
• Patients with history of allergy to GM-CSF or who are unable to obtain GM-CSF because of insurance issues are ineligible

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.