Clinical trial NCT00911560: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Neuroblastoma
Keywords: BETA-D-GLUCAN
OPT-821
GD2-KLH
GD3-KLH
QS 21
Vaccine
05-075
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: Y-mAbs Therapeutics
First posted: 2009-06-02
Enrollment: 374
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: To determine the maximally tolerated dose of OPT-821 in a vaccine containing two antigens abundantly expressed on neuroblastoma. (PHASE I)
timeFrame: 2 years
measure: 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)
timeFrame: 2 years
measure: 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
timeFrame: 2 years
Secondary outcomes:
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)
timeFrame: 2 years
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)
timeFrame: 2 years
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)
timeFrame: 2 years
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)
timeFrame: 2 years
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Brian Kushner, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.