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

Summary

This phase I/II trial studies the side effects and best dose of OPT-821 with vaccine therapy when given together with beta-glucan and how well the regimen works in treating younger patients with high-risk neuroblastoma. 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

PRIMARY OBJECTIVES:

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 second (or later) complete/very good partial remission (CR/VGPR), i.e., have no evidence of neuroblastoma (NB) by standard studies after having received salvage therapy for relapse. (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)

SECONDARY OBJECTIVES:

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 immunological adjuvant OPT-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:

Relapsed high-risk NB (as defined above) and now in 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

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 (> 15 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

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

>= 3 weeks between completion of systemic therapy and first vaccination

Prior treatment with other immunotherapy, including antibodies, is allowed

Patients with less than grade 3 toxicities (using the Common Terminology Criteria for Adverse Events [CTCAE] v3.0) related to cardiac, neurological, pulmonary or gastrointestinal function as determined by physical exam

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

U.S.A.

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.