Bivalent Vaccine With Escalating Doses of the Immunological Adjuvant OPT-821, in Combination With Oral β-glucan for High-Risk Neuroblastoma
The purpose of this study is to test the safety and what effects, good and/or bad, treatment with a vaccine against neuroblastoma has on the patient and the cancer. In the first part of this study we found the highest dose of the vaccine that did not have too many side effects. We are now trying to find out what effects the vaccine has when given at the same dose to all patients.
The main treatment in this protocol is a vaccine. It is called a " bivalent vaccine" which means it has 2 antigens. An antigen is a specific protein on the surface of a cell. The antigens are called GD2L and GD3L.
We want the vaccine to cause the patient's immune system to make antibodies against the antigens. Antibodies are made by the body to attack cancer (and to fight infections). If the patient can make antibodies against the 2 antigens in the vaccine, those antibodies might also attach to neuroblastoma cells because a lot of each antigen is on neuroblastoma (and very little on other parts of the body). Then, the attached antibodies would attract the patient's white blood cells to kill the neuroblastoma. This protocol also uses β-glucan which is a kind of sugar from yeast. β-glucan is taken by mouth and can help white blood cells kill cancer. The best way to get the body to make antibodies against the 3 antigens is to link each antigen to a protein called KLH (which stands for: keyhole limpet hemocyanin) and to mix them with a substance called QS-21. But it is hard to get enough QS-21 so we are using an identical substance called OPT-821, which we can get easily in large amounts for use in patients.
|Neuroblastoma||Biological: adjuvant OPT-821 in a vaccine containing two antigens (GD2L and GD3L) covalently linked to KLH||Phase 1 Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||Phase I/II Trial of a Bivalent Vaccine With Escalating Doses of the Immunological Adjuvant OPT-821, in Combination With Oral β-glucan for High-Risk Neuroblastoma|
- To determine the maximally tolerated dose of OPT-821 in a vaccine containing two antigens abundantly expressed on neuroblastoma. (PHASE I) [ Time Frame: 2 years ]
- 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 NB by standard studies. (PHASE II) [ Time Frame: 2 Years ]
- To assess anti-NB activity of the bivalent vaccine plus oral β-glucan in patients who are enrolled with evidence of minimal residual disease (MRD) by molecular biological testing of bone marrow. (PHASE II) [ Time Frame: 2 years ]
- 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) [ Time Frame: 2 years ]
- To obtain preliminary data on the anti-neuroblastoma activity of the bivalent vaccine plus oral β-glucan in patients, including measuring the molecular response in blood and bone marrow. (PHASE I) [ Time Frame: 2 years ]
- 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) [ Time Frame: 2 years ]
- To assess FcRIIa, FcRIIIa, CR3 and CD18 gene polymorphism of leukocytes (effector cells), with a view towards a possible association with outcome. (PHASE II) [ Time Frame: 2 years ]
|Study Start Date:||May 2009|
|Estimated Study Completion Date:||May 2020|
|Estimated Primary Completion Date:||May 2020 (Final data collection date for primary outcome measure)|
This phase I/II trial in patients with high-risk neuroblastoma (NB) will in phase I assess the toxicity of escalating doses and in phase II the anti-NB activity of, and immune responses to, a vaccine comprised of the immunological adjuvant OPT-821 plus GD2L and GD3L covalently attached to the immunological carrier protein keyhole limpet hemocyanin (KLH) and each abundantly expressed on NB. The patients will take oral β-glucan, which augments neutrophil cytotoxicity. The phase II treatment schema for patients in 1st CR/VGPR (n=40) or >2nd CR/VGPR (n=60) will be the same as in phase I except OPT-821 will be given at a fixed dose of 150 mcg/ m2 and with no DLT assessment.
Biological: adjuvant OPT-821 in a vaccine containing two antigens (GD2L and GD3L) covalently linked to KLH
Patients receive a total of 7 subcutaneous injections, at weeks 1, 2, 3, 8, 20, 32, and 52. Minor schedule adjustments are permitted, as needed, provided that there is a minimum of 6 days between injections. Induction of antibody response against the target antigens will be assessed. A fixed dose of oral β-glucan (40 mg/kg/day) is started at week 6 or 7(to allow time for generation of antibodies), and continued as approximately 2 weeks on, 2 weeks off, up to 1 cycle after the last vaccination. Neutrophils will be tested for glucan effects on cytotoxicity. Antineuroblastoma activity will be monitored using standard radiographic and bone marrow studies, as well as RT-PCR for measurement of minimal residual disease in blood and bone marrow. The treatment schedule may require minor adjustment as clinically indicated or due to unforeseen circumstance (e.g., due to PDH closure for holidays or due to inclement weather).
Please refer to this study by its ClinicalTrials.gov identifier: NCT00911560
|Contact: Brian Kushner, MD||212-639-6793|
|Contact: Nai-Kong Cheung, MD||646-888-2313|
|United States, New York|
|Memorial Sloan Kettering Cancer Center||Recruiting|
|New York, New York, United States, 10065|
|Contact: Brian Kushner, MD 212-639-6793|
|Principal Investigator: Brian Kushner, MD|
|Principal Investigator:||Brian Kushner, MD||Memorial Sloan Kettering Cancer Center|