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

This study is currently recruiting participants.
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Verified May 2017 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 9, 2017
Last verified: May 2017
May 29, 2009
May 9, 2017
May 2009
May 2020   (Final data collection date for primary outcome measure)
  • 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 determine the maximally tolerated dose of OPT-821 in a vaccine containing three antigens abundantly expressed on neuroblastoma. [ Time Frame: 2 years ]
Complete list of historical versions of study NCT00911560 on ClinicalTrials.gov Archive Site
  • 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 ]
  • To obtain preliminary data on whether subcutaneous administration of the trivalent vaccine produces an immune response directed against the target antigens in patients with high-risk neuroblastoma. [ Time Frame: 2 years ]
  • To obtain preliminary data on the anti-neuroblastoma activity of the trivalent vaccine plus oral β-glucan in patients, including measuring the molecular response in blood and bone marrow. [ Time Frame: 2 years ]
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Not Provided
 
Bivalent Vaccine With Escalating Doses of the Immunological Adjuvant OPT-821, in Combination With Oral β-glucan for High-Risk Neuroblastoma
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

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.

Not Provided
Interventional
Phase 1
Phase 2
Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Neuroblastoma
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).
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. 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.
Intervention: Biological: adjuvant OPT-821 in a vaccine containing two antigens (GD2L and GD3L) covalently linked to KLH
Kushner BH, Cheung IY, Modak S, Kramer K, Ragupathi G, Cheung NK. Phase I trial of a bivalent gangliosides vaccine in combination with β-glucan for high-risk neuroblastoma in second or later remission. Clin Cancer Res. 2014 Mar 1;20(5):1375-82. doi: 10.1158/1078-0432.CCR-13-1012. Epub 2014 Feb 11.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
145
May 2020
May 2020   (Final data collection date for primary outcome measure)

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.
  • High-risk NB (as defined above) and in 1) first CR/VGPR by approximately 6 months from initiation of immunotherapy using 3F8 or other anti-GD2 mAbs, or 2) 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 ≥ 500/mcl and 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 USA (CTCAE v3.0) related to cardiac, neurological, pulmonary, renal, hepatic or gastrointestinal function as determined by blood tests or physical exam.
  • ALT, AST and Alkaline Phosphatase ≤ 2.5 times the upper limit of normal
  • Prior treatment with other immunotherapy, including antibodies, is allowed
  • ≥ 3 weeks between completion of chemotherapy or immunotherapy 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.
Sexes Eligible for Study: All
up to 21 Years   (Child, Adult)
No
Contact: Brian Kushner, MD 212-639-6793
Contact: Nai-Kong Cheung, MD 646-888-2313
United States
 
 
NCT00911560
05-075
Not Provided
Not Provided
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Memorial Sloan Kettering Cancer Center
Memorial Sloan Kettering Cancer Center
Not Provided
Principal Investigator: Brian Kushner, MD Memorial Sloan Kettering Cancer Center
Memorial Sloan Kettering Cancer Center
May 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP