OPT-821 with Vaccine Therapy and Beta-Glucan in Treating Younger Patients with High-Risk Neuroblastoma

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Basic Trial Information

PhaseTypeAgeTrial IDs
Phase II, Phase ITreatment21 and under05-075
NCI-2009-01362, NCT00911560

Trial Description


This phase I/II trial studies the side effects and best dose of OPT-821 (saponin-based immunoadjuvant OBI-821) with vaccine therapy when given together with beta-glucan and how well the regimen works in treating younger patients with neuroblastoma that is likely to recur (come back), or spread (high-risk). Biological therapies, such as OPT-821 and beta-glucan, may stimulate the immune system in different ways and stop tumor cells from growing. Vaccines may help the body build an effective immune response to kill tumor cells. Giving OPT-821 with vaccine therapy together with beta-glucan may be an effective treatment for high-risk neuroblastoma.

Further Study Information


I. To determine the maximally tolerated dose of OPT-821 in a vaccine containing two antigens abundantly expressed on neuroblastoma. (Phase I)

II. To improve event-free survival (EFS) of patients who are in first or second (or later) complete/very good partial remission (CR/VGPR), i.e., have no evidence of neuroblastoma (NB) by standard studies. (Phase II)

III. To assess anti-NB activity of the bivalent vaccine plus oral beta-glucan in patients who are enrolled with evidence of minimal residual disease (MRD) by molecular biological testing of bone marrow. (Phase II)


I. To obtain preliminary data on whether subcutaneous administration of the bivalent vaccine produces an immune response directed against the target antigens in patients with high-risk neuroblastoma. (Phase I)

II. To obtain preliminary data on the anti-neuroblastoma activity of the bivalent vaccine plus oral beta-glucan in patients, including measuring the molecular response in blood and bone marrow. (Phase I)

III. To obtain data on the immune response directed against the target NB-associated antigens in patients as induced by the subcutaneous administration of the bivalent vaccine.

IV. To assess Fc fragment of immunoglobulin G (IgG), low affinity IIa, receptor (FcRIIa), Fc fragment of IgG, low affinity IIIa, receptor (FcRIIIa), integrin, alpha M (complement component 3 receptor 3 subunit) (CR3) and cluster of differentiation (CD)18 gene polymorphism of leukocytes (effector cells), with a view towards a possible association with outcome.

OUTLINE: This is a phase I, dose-escalation study of OPT-821 followed by a phase II study.

Patients receive a bivalent antigen keyhole limpet hemocyanin (KLH) conjugate vaccine and saponin-based immunoadjuvant OBI-821 (vaccine containing two antigens [GD2L, GD3L]) subcutaneously (SC) in weeks 1, 2, 3, 8, 20, 32, and 52 in the absence of disease progression or unacceptable toxicity. Beginning on week 6 or 7, patients also receive beta-glucan orally (PO) once daily (QD) for approximately 2 weeks on and 2 weeks off. Treatment with beta-glucan repeats up to 1 course after the last vaccination in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years.

Eligibility Criteria

Inclusion Criteria:

>= 3 weeks between completion of systemic therapy and first (1st) vaccination

Patients with less than grade 3 toxicities using the Common Terminology Criteria (version 3.0) developed by the National Cancer Institute of the United States of America (USA) (Common Terminology Criteria for Adverse Events [CTCAE] version [v]3.0) related to cardiac, neurological, pulmonary or gastrointestinal function as determined by physical exam

High-risk NB as defined by risk-related treatment guidelines and the International NB Staging System, i.e., stage 4 with (any age) or without (> 18 months old) myelocytomatosis viral related oncogene (MYCN) amplification, MYCN-amplified stage 3 (unresectable; any age), MYCN-amplified stage 4S, or disease resistant to standard chemotherapy

High-risk NB (as defined above) and now in 1) first CR/VGPR at 6 months from initiation of immunotherapy using anti-GD2 mAbs, or 2) second or subsequent remission; remission is defined as complete (CR) or very good partial (VGPR) remission, according to the International Neuroblastoma Response Criteria; urine catecholamine levels are no longer taken into consideration when staging; patients can be considered as in VGPR with 1 or 2 MIBG (+) sites that were previously-irradiated

Alkaline phosphatase =< 2.5 times the upper limit of normal

Absolute neutrophil count >= 500/mcl

Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 times the upper limit of normal

Absolute lymphocyte count >= 500/mcl

Diagnosis of neuroblastoma (NB) as defined by international criteria, i.e., histopathology (confirmed by the Memorial Sloan-Kettering Cancer Center [MSKCC] Department of Pathology) or bone marrow metastases plus high urine catecholamine levels

Signed informed consent indicating awareness of the investigational nature of this program

Prior treatment with other immunotherapy, including antibodies, is allowed

Bilirubin =< 2.0 mg/dL

Creatinine =< 2.0 mg/dL

Exclusion Criteria:

Inability to comply with protocol requirements

Active life-threatening infection

History of allergy to KLH, QS-21, OPT-821, or glucan

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

Memorial Sloan-Kettering Cancer Center

  • National Cancer Institute
Brian Harris Kushner, Principal Investigator

Trial Sites


New York
New York

Memorial Sloan-Kettering Cancer Center

Brian Harris Kushner
Ph: 212-639-6793
Email: kushnerb@mskcc.org

Brian Harris Kushner
Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00911560

Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.