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

Status: Active

Description

This randomized 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.

Eligibility Criteria

Inclusion Criteria

  • 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 (> 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 in 1) first CR at >= 6 months from initiation of immunotherapy using anti-GD2 antibody, or 2) second or subsequent remission; remission is defined as complete (CR) remission, according to the International Neuroblastoma Response Criteria; urine catecholamine levels are no longer taken into consideration when staging
  • Absolute lymphocyte count >= 500/mcl
  • Absolute neutrophil count >= 500/mcl
  • Patients with grade 3 toxicities or less using the Common Toxicity Criteria (version 3.0) developed by the National Cancer Institute of the United States of America (USA) (Common Terminology Criteria for Adverse Events version 3.0) related to cardiac, neurological, pulmonary, renal, hepatic or gastrointestinal function as determined by blood tests or physical exam
  • Prior treatment with other immunotherapy, including antibodies, is allowed
  • >= 3 weeks between completion of chemotherapy or immunotherapy and first (1st) vaccination
  • Signed informed consent indicating awareness of the investigational nature of this program

Exclusion Criteria

  • History of allergy to KLH, QS-21, OPT-821, or glucan
  • Active life-threatening infection
  • Inability to comply with protocol requirements

Locations & Contacts

New York

New York
Memorial Sloan Kettering Cancer Center
Status: Active
Contact: Brian Harris Kushner
Phone: 212-639-6793

Trial Objectives and Outline

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 assess anti-neuroblastoma (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)

III. To prove the adjuvant effect of oral beta-glucan on anti-GD2 antibody titer among patients who are in first or second (or later) complete (CR), i.e., have no evidence of NB by standard studies. (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 saponin-based immunoadjuvant OBI-821 followed by a phase II study. Patients are randomized to 1 of 2 groups.

GROUP I: Patients receive GD2 lactone/GD3 lactone-keyhole limpet hemocyanin (KLH) conjugate bivalent vaccine and saponin-based immunoadjuvant OBI-821 subcutaneously (SC) on weeks 1, 2, 3, 8, 20, 32, and 52 in the absence of disease progression or unacceptable toxicity. Beginning week 6 or 7, patients also receive beta-glucan orally (PO) once daily (QD) for approximately 2 weeks on and 2 weeks off up to 1 course after the last vaccination in the absence of disease progression or unacceptable toxicity.

GROUP II: Patients receive GD2 lactone/GD3 lactone-KLH conjugate bivalent vaccine and saponin-based immunoadjuvant OBI-821 SC on weeks 1, 2, 3, 8, 20, 32, and 52 in the absence of disease progression or unacceptable toxicity. Beginning week 1, patients also receive beta-glucan PO QD for approximately 2 weeks on and 2 weeks off 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 then every 6 months for up to 5 years.

Trial Phase & Type

Trial Phase

Phase I/II

Trial Type

Treatment

Lead Organization

Lead Organization
Memorial Sloan Kettering Cancer Center

Principal Investigator
Brian Harris Kushner

Trial IDs

Primary ID 05-075
Secondary IDs NCI-2009-01362
Clinicaltrials.gov ID NCT00911560