Vaccine + Beta-glucan for Neuroblastoma

Recruiting at 6 trial locations

Overseen By Fiorella Iglasias Cardenas, MD, MS

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Grade 4 toxicities, Allergy, Infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

94 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine which schedule of a bivalent vaccine combined with β-glucan (a natural compound) works best for individuals with high-risk neuroblastoma currently in complete remission. The study includes two groups with different treatment timelines to assess which schedule yields better outcomes. Participants must have high-risk neuroblastoma that is inactive after recent treatment and should not have serious organ issues. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators for more details.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that β-glucan is safe and well-tolerated in people. Studies demonstrated that even at doses up to 200 mg/kg, no major side effects occurred. For over ten years, it has been used in children without significant safety concerns.

The bivalent vaccine in the study has also undergone previous testing. Research identified the highest dose that children could handle without excessive side effects. This vaccine helps the immune system recognize and fight neuroblastoma, a type of cancer.

In summary, previous studies have shown both β-glucan and the bivalent vaccine to be safe. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for neuroblastoma, which typically involve chemotherapy, radiation, and surgery, the new investigational treatment combines a bivalent vaccine with β-glucan. This approach stands out because the vaccine aims to train the immune system to target cancer cells more effectively, while β-glucan, a natural compound derived from fungi, is known to boost immune response. Researchers are excited because this combination could potentially enhance the body's ability to fight cancer with fewer side effects than conventional therapies. By leveraging the immune system in a novel way, this treatment offers a promising new avenue for managing neuroblastoma.

What evidence suggests that this trial's treatments could be effective for high-risk neuroblastoma in complete remission?

Research has shown that the bivalent vaccine for neuroblastoma has produced promising results in patients. However, its effectiveness remains uncertain due to the complexity of previous treatments. In contrast, beta-glucan, a natural substance, can enhance the body's immune system. It aids white blood cells in fighting cancer by improving their ability to kill cancer cells. Studies have suggested that beta-glucans can also enhance the effectiveness of other cancer treatments. This trial tests the vaccine and beta-glucan together in different treatment groups to determine if they can be more effective for people with high-risk neuroblastoma. ^{4 6 7 8 9}

Who Is on the Research Team?

Brian Kushner, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for people with high-risk neuroblastoma in complete remission. Participants must have a certain level of lymphocytes and neutrophils, be within specific time frames post-therapy, and able to consent. Pregnant individuals or those with severe organ dysfunction, allergies to the vaccine components, or inability to follow protocol are excluded.

Inclusion Criteria

Your absolute lymphocyte count is 500/mcl or higher.

Patients with the potential to bear children must provide a negative pregnancy test.

Absolute neutrophil count (ANC) ≥ 500/mcl

Exclusion Criteria

My blood tests and physical exams show no severe issues with my heart, lungs, kidneys, liver, or blood.

I have previously received this vaccine.

I do not have a severe infection needing treatment through my veins.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral β-glucan and bivalent vaccine. Group 1 receives β-glucan for 14 days on, 14 days off for ~20 weeks, then one 14-day cycle with each of vaccinations #6-#10. Group 2 continues until vaccination #7 (~52 weeks), then one 14-day cycle with each of vaccinations #8-#10.

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Beta-glucan
• Bivalent Vaccine

Trial Overview The study is testing different treatment schedules of β-glucan combined with a bivalent vaccine (OPT-821/QS-21) on patients who have high-risk neuroblastoma but are currently in complete remission. The goal is to find out which schedule might be more effective.

How Is the Trial Designed?

Group I: Group 2 Experimental Treatment 2 Interventions

Participants will receive oral β-glucan (40 mg/kg/day) for 14 days on, and 14 days off, beginning with vaccination #1 and continuing until vaccination #7 (\~52 weeks), then only one 14-day cycle with each of vaccinations #8-#10.

Group II: Group 1 Experimental Treatment 2 Interventions

Participants will receive oral β-glucan (40 mg/kg/day) for 14 days on, and 14 days off, beginning with vaccination #1 and continuing until vaccination #5 (\~20 weeks), then only one 14-day cycle with each of vaccinations #6-#10.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

The phase I trial of the immunologic adjuvant OPT-821 in children with neuroblastoma showed no dose-limiting toxicity at the maximum dose of 150 μg/m², indicating it is safe for use in this population.

Eighty percent of patients remained relapse-free at 24 months, and six out of ten patients showed disappearance of minimal residual disease, suggesting promising preliminary efficacy of the vaccine combined with β-glucan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of a bivalent gangliosides vaccine in combination with β-glucan for high-risk neuroblastoma in second or later remission. Kushner, BH., Cheung, IY., Modak, S., et al.[2021]

The combination of the anti-GD2 antibody 3F8 and oral barley-derived β-glucan (BG) was found to be well tolerated in a Phase I clinical study involving 24 patients with chemoresistant neuroblastoma, with only two cases of dose-limiting toxicity (grade 4 thrombocytopenia).

Clinical improvements were observed in 13 out of 22 patients with positive scans, indicating that this treatment regimen may have antineoplastic activity, although responses did not correlate with the dose of BG or in vitro cytotoxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-GD2 antibody 3F8 and barley-derived (1 → 3),(1 → 4)-β-D-glucan: A Phase I study in patients with chemoresistant neuroblastoma. Modak, S., Kushner, BH., Kramer, K., et al.[2021]

Immunotherapy using dinatuximab beta (Qarziba®), which targets the GD2 ganglioside found on neuroblastoma cells, has shown effectiveness in improving survival rates for high-risk neuroblastoma patients, particularly when used as a first-line maintenance treatment.

Current research is focused on combining dinatuximab beta with chemotherapy for relapsed cases and developing more selective antibodies to reduce side effects, such as neuropathic pain, which is a significant concern in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Anti-GD2 antibodies in treatment of high-risk Neuroblastoma: present and perspectives]. Valteau-Couanet, D., Minard-Colin, V., Pasqualini, C.[2022]

In a phase I study involving 44 patients with relapsed or refractory high-risk neuroblastoma, the combination of yeast-derived beta glucan (BG) and the anti-GD2 monoclonal antibody 3F8 showed promising anti-tumor responses, with 1 complete response and several partial responses observed.

The treatment was well-tolerated, with only one case of transient liver enzyme elevation, and the study recommended a phase II dose of 40 mg/kg/day for BG, as it did not reach a maximum tolerated dose and lacked major toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Trial of Oral Yeast-Derived β-Glucan to Enhance Anti-GD2 Immunotherapy of Resistant High-Risk Neuroblastoma. Cardenas, FI., Mauguen, A., Cheung, IY., et al.[2022]

A novel DNA vaccine targeting the GD2 ganglioside, combined with IL-15 and IL-21, significantly enhanced the immune response against neuroblastoma in a mouse model, leading to effective tumor growth inhibition.

The study showed that both innate (NK cells) and adaptive (CD8(+) T cells) immune responses were crucial for the vaccine's efficacy, indicating a comprehensive immune activation strategy against a weakly immunogenic tumor antigen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induction of protective immune responses against NXS2 neuroblastoma challenge in mice by immunotherapy with GD2 mimotope vaccine and IL-15 and IL-21 gene delivery. Kowalczyk, A., Wierzbicki, A., Gil, M., et al.[2018]

The ganglidiomab vaccine, used in seven high-risk neuroblastoma patients after treatment with anti-GD2 monoclonal antibodies, was well-tolerated with no severe side effects, indicating its safety for use in this population.

Six out of seven patients developed a specific immune response to the vaccine, and notably, none of the immunized patients experienced relapses or disease progression, suggesting potential efficacy in preventing neuroblastoma recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune Response and Outcome of High-Risk Neuroblastoma Patients Immunized with Anti-Idiotypic Antibody Ganglidiomab: Results from Compassionate-Use Treatments. Klingel, L., Siebert, N., Troschke-Meurer, S., et al.[2022]

In a phase II study involving 102 patients with high-risk neuroblastoma, the GD2/GD3 vaccine combined with oral β-glucan demonstrated a favorable safety profile, with only mild, self-limited side effects and no severe toxicities.

Higher levels of anti-GD2-IgG1 antibodies (≥ 150 ng/mL) by week 8 were linked to better progression-free survival (32% at 5 years) and overall survival (71% at 5 years), indicating that antibody response may be a key factor in treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival Impact of Anti-GD2 Antibody Response in a Phase II Ganglioside Vaccine Trial Among Patients With High-Risk Neuroblastoma With Prior Disease Progression. Cheung, IY., Cheung, NV., Modak, S., et al.[2022]

In a phase 2 clinical trial involving 107 children with high-risk neuroblastoma, adding oral β-glucan during the first 5 weeks of GD2/GD3 vaccine priming resulted in a higher anti-GD2 IgG1 antibody response, suggesting it may enhance the vaccine's effectiveness.

The study found that while β-glucan increased antibody titers, it did not lead to a significant difference in seroconversion rates or additional toxic effects, indicating that further research is needed to find more effective adjuvants for improving immune responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Oral β-Glucan on Antibody Response to Ganglioside Vaccine in Patients With High-Risk Neuroblastoma: A Phase 2 Randomized Clinical Trial. Cheung, IY., Mauguen, A., Modak, S., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9936346/

Effect of Oral β-Glucan on Antibody Response to ... Survival Outcomes Among Patients With High-Risk Neuroblastoma Who Began Receiving β-Glucan at Week 1 (Group 2) vs at Week 6 (Group 1).

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06057948?cond=Neuroblastoma%20OR%20%22neural%20Crest%20tumor,%20malignant%22%20OR%20%22%20neuroblastoma%20(Schwannian%20Stroma-poor)%22%20OR%20%22%20neuroblastoma,%20malignant%22&aggFilters=status:not%20rec&viewType=Table&rank=6

NCT06057948 | A Study of a Vaccine in Combination With ... The purpose of this study is to test which treatment schedule of β-glucan with bivalent vaccine is more effective for participants with high-risk neuroblastoma ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8699451/

Phase I Trial of Oral Yeast-Derived β-Glucan to Enhance ... Beta glucans, complex polysaccharides, can prime leukocyte dectin-1 and CR3-receptors and enhance anti-tumor cytotoxicity of monoclonal antibodies.

4. sciencedirect.com sciencedirect.com/org/science/article/pii/S1573493524000523

Potential promising anticancer applications of β-glucans Furthermore, β-glucans have shown potential in enhancing the efficacy of conventional cancer treatments, such as chemotherapy and radiotherapy.

5. portlandpress.com portlandpress.com/bioscirep/article/44/1/BSR20231686/233829/Potential-promising-anticancer-applications-of

Potential promising anticancer applications of β-glucans Studies have indicated that they can inhibit cancer cell growth, induce apoptosis (programmed cell death) in cancer cells, and impede the formation of new blood ...

6. jhoonline.biomedcentral.com jhoonline.biomedcentral.com/articles/10.1186/1756-8722-2-25

The effects of β-glucan on human immune and cancer cells Current data suggests that β-glucans are potent immunomodulators with effects on both innate and adaptive immunity. The ability of the innate ...

7. spandidos-publications.com spandidos-publications.com/10.3892/or.2021.8225

β‑glucan vaccine adjuvant approach for cancer treatment ... β-glucans, as a result of their high biocompatibility and tolerability and satisfactory safety profile, possess numerous beneficial properties, ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5069311/

Beta-glucan contamination of pharmaceutical products Accordingly, a limit of 10 ng/mg (or 500 ng total dose) of beta-glucans is considered to pose a low risk to patients, and this specification was ...

9. mdpi.com mdpi.com/2072-6694/13/24/6265

Phase I Trial of Oral Yeast-Derived β-Glucan to Enhance ... We demonstrated that the combination of BG and 3F8 is safe, even with BG doses of up to 200 mg/kg/dose. There were no major adverse events ...