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.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT00911560.
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(B)-glucan on anti-GD2 antibody titer among patients who are in first or second (or later) complete remission (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. (Phase II)
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. (Phase II)
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. Patients who have previously received vaccine and beta-glucan are assigned to group I.
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 cycle 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 cycle 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.
Lead OrganizationMemorial Sloan Kettering Cancer Center
Principal InvestigatorBrian Harris Kushner
