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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

NCT00911560

Description:

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 2 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.

Related Conditions:
  • Neuroblastoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 05-075
  • NCT ID: NCT00911560

Conditions

  • Neuroblastoma

Interventions

DrugSynonymsArms
adjuvant OPT-821 in a vaccine containing two antigens (GD2L and GD3L) covalently linked to KLHvaccine
oral β-glucanvaccine

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 2 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.

Detailed Description

      The phase II treatment schema for patients in 1st CR or >2nd CR will be the same for the
      vaccine as in phase I except OPT-821 will be given at a fixed dose of 150 mcg/ m^2 and with
      no DLT assessment. Patients will be randomized to starting oral β-glucan in week 1 or in week
      6.
    

Trial Arms

NameTypeDescriptionInterventions
vaccineExperimentalThis 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
  • adjuvant OPT-821 in a vaccine containing two antigens (GD2L and GD3L) covalently linked to KLH
  • oral β-glucan

Eligibility 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 MYCN amplification (any age) stage 4 >18
             months old.

          -  High-risk NB (as defined above) and in 1) first CR at 6 ≥ months from initiation of
             immunotherapy using anti-GD2 antibody, or 2) second or subsequent remission. Remission
             is defined as complete (CR) remission, according to the International Neuroblastoma
             Response Criteria.[104] Urine catecholamine levels are no longer taken into
             consideration when staging.

          -  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.
      
Maximum Eligible Age:21 Years
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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
Safety Issue:
Description:

Secondary Outcome Measures

Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • BETA-D-GLUCAN
  • OPT-821
  • GD2-KLH
  • GD3-KLH
  • QS 21
  • Vaccine
  • 05-075

Last Updated

December 23, 2019