Back to resultsBivalent Vaccine With Escalating Doses of the Immunological Adjuvant OPT-821, in Combination With Oral β-glucan for High-Risk Neuroblastoma
Primary Purpose
Neuroblastoma
Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
adjuvant OPT-821 in a vaccine containing two antigens (GD2L and GD3L) covalently linked to KLH
oral β-glucan
Sponsored by
About this trial
This is an interventional treatment trial for Neuroblastoma focused on measuring BETA-D-GLUCAN, OPT-821, GD2-KLH, GD3-KLH, QS 21, Vaccine, 05-075
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.
Sites / Locations
- Memorial Sloan Kettering Cancer Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
vaccine group one
vaccine group two
vaccine group three
Arm Description
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 .
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 .
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.
Outcomes
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 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)
To prove the adjuvant effect of oral beta-glucan on anti-GD2 antibody titer among patients who are in first or second (or later) complete
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 β-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)
Full Information
NCT ID
NCT00911560
First Posted
May 29, 2009
Last Updated
June 1, 2023
Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
Y-mAbs Therapeutics
1. Study Identification
Unique Protocol Identification Number
NCT00911560
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
May 27, 2009 (Actual)
Primary Completion Date
May 2025 (Anticipated)
Study Completion Date
May 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
Y-mAbs Therapeutics
4. Oversight
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuroblastoma
Keywords
BETA-D-GLUCAN, OPT-821, GD2-KLH, GD3-KLH, QS 21, Vaccine, 05-075
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
374 (Actual)
8. Arms, Groups, and Interventions
Arm Title
vaccine group one
Arm Type
Experimental
Arm Description
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 .
Arm Title
vaccine group two
Arm Type
Experimental
Arm Description
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 .
Arm Title
vaccine group three
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
adjuvant OPT-821 in a vaccine containing two antigens (GD2L and GD3L) covalently linked to KLH
Intervention Description
Pts receive a total of 7 subcutaneous injections, at weeks 1, 2, 3, 8, 20, 32, & 52. Minor schedule adjustments are permitted, as needed. Vaccines must occur a minimum of 6 days apart. 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), & 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 & bone marrow studies, as well as RT-PCR for measurement of minimal residual disease in blood & bone marrow. Phase II treatment schema for patients in 1st CR/VGPR or >2nd CR/VGPR will be the same for the vaccine as in phase I except OPT-821 will be given at a fixed dose of 150 mcg/m2.
Intervention Type
Biological
Intervention Name(s)
oral β-glucan
Intervention Description
Phase II Patients will be randomized to starting oral β-glucan (40 mg/kg/day) in week 1 or in week 6.
Primary Outcome Measure Information:
Title
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
Title
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
Title
To prove the adjuvant effect of oral beta-glucan on anti-GD2 antibody titer among patients who are in first or second (or later) complete
Time Frame
2 years
Secondary Outcome Measure Information:
Title
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
Title
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
Title
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
Title
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
10. Eligibility
Sex
All
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Brian Kushner, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
33326254
Citation
Cheung IY, Cheung NV, Modak S, Mauguen A, Feng Y, Basu E, Roberts SS, Ragupathi G, Kushner BH. Survival Impact of Anti-GD2 Antibody Response in a Phase II Ganglioside Vaccine Trial Among Patients With High-Risk Neuroblastoma With Prior Disease Progression. J Clin Oncol. 2021 Jan 20;39(3):215-226. doi: 10.1200/JCO.20.01892. Epub 2020 Dec 16. Erratum In: J Clin Oncol. 2021 Feb 1;39(4):341.
Results Reference
derived
PubMed Identifier
24520094
Citation
Kushner BH, Cheung IY, Modak S, Kramer K, Ragupathi G, Cheung NK. Phase I trial of a bivalent gangliosides vaccine in combination with beta-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.
Results Reference
derived
Links:
URL
http://www.mskcc.org/mskcc/html/44.cfm
Description
Memorial Sloan Kettering Cancer Center
Learn more about this trial
Bivalent Vaccine With Escalating Doses of the Immunological Adjuvant OPT-821, in Combination With Oral β-glucan for High-Risk Neuroblastoma
We'll reach out to this number within 24 hrs