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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:

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.

Related Conditions:
  • Neuroblastoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Bivalent Vaccine With Escalating Doses of the Immunological Adjuvant OPT-821, in Combination With Oral -glucan for High-Risk <span class="go-doc-concept go-doc-disease">Neuroblastoma</span>

Title

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

    NCT ID: NCT00911560

    ORG ID: 05-075

    Trial Conditions

    Neuroblastoma

    Trial Interventions

    Drug Synonyms Arms

    Trial 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 -glucan
    which is a kind of sugar from yeast. -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.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    vaccine Experimental 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 -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.

    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 (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 now in 1) first CR/VGPR at 6 months from
    initiation of immunotherapy using 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 > 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.

    Minimum Eligible Age: N/A

    Maximum Eligible Age: 21 Years

    Eligible Gender: Both

    Primary Outcome Measures

    To determine the maximally tolerated dose of OPT-821 in a vaccine containing two antigens abundantly expressed on neuroblastoma. (PHASE I)

    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)

    To assess anti-NB activity of the bivalent vaccine plus oral -glucan in patients who are enrolled with evidence of minimal residual disease (MRD) by molecular biological testing of bone marrow. (PHASE II)

    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)

    To obtain preliminary data on the anti-neuroblastoma activity of the bivalent vaccine plus oral -glucan in patients, including measuring the molecular response in blood and bone marrow. (PHASE I)

    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)

    To assess FcRIIa, FcRIIIa, CR3 and CD18 gene polymorphism of leukocytes (effector cells), with a view towards a possible association with outcome. (PHASE II)

    Trial Keywords

    BETA-D-GLUCAN

    OPT-821

    GD2-KLH

    GD3-KLH

    QS 21

    Vaccine

    05-075