Bivalent Vaccine With Escalating Doses of the Immunological Adjuvant OPT-821, in Combination With Oral β-glucan for High-Risk Neuroblastoma
| Status: | Recruiting |
|---|---|
| Conditions: | Brain Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | Any - 21 |
| Updated: | 3/2/2019 |
| Start Date: | May 2009 |
| End Date: | May 2020 |
| Contact: | Brian Kushner, MD |
| Phone: | 212-639-6793 |
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 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.
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.
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.
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.
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 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.
We found this trial at
1
site
1275 York Ave
New York, New York 10021
New York, New York 10021
(212) 639-2000
Principal Investigator: Brian Kushner, MD
Phone: 212-639-6793
Memorial Sloan Kettering Cancer Center Memorial Sloan Kettering Cancer Center — the world's oldest and...
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