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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00911560
First received: May 29, 2009
Last updated: May 21, 2014
Last verified: May 2014
  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:


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 2015
Estimated Primary Completion Date: May 2015 (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).

  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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:
No publications provided by Memorial Sloan-Kettering Cancer Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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 21, 2014
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 August 18, 2014