Bivalent Vaccine With Escalating Doses of the Immunological Adjuvant OPT-821, in Combination With Oral ß-glucan for High-Risk Neuroblastoma - Full Text View

Purpose

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.

Condition	Intervention	Phase
Neuroblastoma	Biological: adjuvant OPT-821 in a vaccine containing two antigens (GD2L and GD3L) covalently linked to KLH	Phase 1 Phase 2

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label 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 ß-glucan for High-Risk Neuroblastoma

Resource links provided by NLM:

Genetics Home Reference related topics: neuroblastoma

MedlinePlus related topics: Cancer Neuroblastoma

U.S. FDA Resources

Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:

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 ] [ Designated as safety issue: Yes ]
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 NB by standard studies after having received salvage therapy for relapse. (PHASE II) [ Time Frame: 2 Years ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]

Estimated Enrollment:	45
Study Start Date:	May 2009
Estimated Study Completion Date:	May 2014
Estimated Primary Completion Date:	May 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: vaccine 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.	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. 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).

Arms

Assigned Interventions

Experimental: vaccine

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.

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. 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).

Eligibility

Ages Eligible for Study:	up to 21 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Diagnosis of neuroblastoma (NB) as defined by international criteria,[104] i.e., histopathology (confirmed by the 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,[104] i.e., stage 4 with (any age) or without (>18 months old) MYCN amplification, MYCN-amplified stage 3 (unresectable; any age), MYCN-amplified stage 4S, or disease resistant to standard chemotherapy.
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.[104] 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.

Absolute lymphocyte count > or = to 500/mcl and absolute neutrophil count > or = to 500/mcl.
Creatinine ≤ 2.0 mg/dL
ALT, AST and Alkaline Phosphatase ≤ 2.5 times the upper limit of normal
Bilirubin ≤ 2.0 mg/dL
Patients with less than grade 3 toxicities (using the CTCAE v3.0) related to cardiac, neurological, pulmonary or gastrointestinal function as determined by physical exam.
Prior treatment with other immunotherapy, including antibodies, is allowed
> or = to 3 weeks between completion of systemic therapy and 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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00911560

Contacts

Contact: Brian Kushner, MD	212-639-6793
Contact: Nai-Kong Cheung, MD	646-888-2313

Locations

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

Sponsors and Collaborators

Memorial Sloan-Kettering Cancer Center

Investigators

Principal Investigator:

Brian Kushner, MD

Memorial Sloan-Kettering Cancer Center

More Information

Additional Information:

Memorial Sloan-Kettering Cancer Center This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:	NCT00911560 History of Changes
Other Study ID Numbers:	05-075
Study First Received:	May 29, 2009
Last Updated:	May 20, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:

BETA-D-GLUCAN
OPT-821
GD2-KLH
GD3-KLH

QS 21
Vaccine
05-075

Additional relevant MeSH terms:

Neuroblastoma
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type

Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on June 18, 2013