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.
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
Interventions
| Drug | Synonyms | Arms |
|---|
| adjuvant OPT-821 in a vaccine containing two antigens (GD2L and GD3L) covalently linked to KLH | | vaccine group one |
| oral β-glucan | | vaccine group one |
Purpose
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
| Name | Type | Description | Interventions |
|---|
| vaccine group one | Experimental | Patients will receive a total of 7 subcutaneous injections, at weeks 1, 2, 3, 8 , 20 , 32 , and 52. Minor schedule adjus tment s are permitted , as needed Vaccines must occur a inimum of 6 days apart. The last three vaccine s can be administered up to one week earlier or later than indicated without representing a protocol violation.Patients assigned to in Group 1 will receive o ral β glucan (40 mg/kg/day) starting at week 6 or 7 and continue with approximately 2 weeks on, 2 weeks off, up to 1 cycle after the last vaccination . | - adjuvant OPT-821 in a vaccine containing two antigens (GD2L and GD3L) covalently linked to KLH
- oral β-glucan
|
| vaccine group two | Experimental | Patients will receive a total of 7 subcutaneous injections, at weeks 1, 2, 3, 8 , 20 , 32 , and 52. Minor schedule adjus tment s are permitted , as needed Vaccines must occur a minimum of 6 days apart. The last three vaccine s can be administered up to one week earlier or later than indicated without representing a protocol violation.Patients assigned to Group 2 will receive oral β glucan (40 mg/kg/day) starting week 1 and continue with approximately 2 weeks on, 2 weeks off, up to 1 cycle after the last vaccination . | - adjuvant OPT-821 in a vaccine containing two antigens (GD2L and GD3L) covalently linked to KLH
- oral β-glucan
|
| vaccine group three | Experimental | Patients will receive a total of 7 subcutaneous injections, at weeks 1, 2, 3, 8 , 20 , 32 , and 52. Minor schedule adjus tment s are permitted , as needed Vaccines must occur a minimum of 6 days apart. The last three vaccine s can be administered up to one week earlier or later than indicated without representing a protocol violation.Group 3 will include patients who have previously received vaccine and oral β glucanglucan. Patients in this group will not be randomized using the MSK CRDB system. They will be treated as patients in Group 1 and receive o ral β glucan (40 mg/kg/day) starting at week 6 or 7 and continue with approximately 2 weeks on, 2 weeks off, up to 1 cycle after the last vaccination . They will not be eligible for primary endpoint. | - 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 and no more than 6 months (<180 days) between completion of systemic therapy
and 1st vaccination.
- Patients previously enrolled on this trial are eligible for repeat enrollment but will
be assigned to treatment as per the control arm (Group 1) and will not be included in
the biostatistical analyses.
- 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
August 5, 2021
