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

Trial Summary

What is the purpose of this trial?

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 that is in complete remission.

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.

What evidence supports the effectiveness of the treatment combining a vaccine and beta-glucan for neuroblastoma?

Research shows that oral beta-glucan, when used with a GD2/GD3 ganglioside vaccine, can stimulate an antibody response in patients with high-risk neuroblastoma, which is linked to improved survival. Additionally, a study found that combining beta-glucan with an anti-GD2 antibody showed antineoplastic (cancer-fighting) activity in patients with advanced-stage neuroblastoma. ^{1 2 3 4 5}

Is the combination of Vaccine and Beta-glucan safe for treating neuroblastoma?

The combination of Vaccine and Beta-glucan has been generally well-tolerated in clinical trials for neuroblastoma, with most patients experiencing no severe side effects. However, in one study, two patients developed severe low platelet counts (thrombocytopenia) at higher doses, which improved with treatment. Overall, the treatment shows a favorable safety profile. ^{1 2 3 4 6}

How is the Vaccine + Beta-glucan treatment for neuroblastoma different from other treatments?

This treatment is unique because it combines a bivalent vaccine targeting specific neuroblastoma antigens (GD2 and GD3) with beta-glucan, an immune-boosting substance, to enhance the body's immune response against the cancer. Unlike traditional treatments, this approach aims to stimulate the immune system to fight the cancer more effectively. ^{1 2 4 7 8}

Research Team

Brian Kushner, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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]

References

1. United States 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. [2021]

2. United States 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. [2021]

3. United States 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. [2022]

4. United States 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. [2023]

5. France pubmed.ncbi.nlm.nih.gov

[Anti-GD2 antibodies in treatment of high-risk Neuroblastoma: present and perspectives]. [2022]

6. Switzerland 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. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Phase I Trial of Oral Yeast-Derived β-Glucan to Enhance Anti-GD2 Immunotherapy of Resistant High-Risk Neuroblastoma. [2022]

8. Germany 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. [2018]