Vaccine + β-glucan + GM-CSF for Neuroblastoma

Overseen By Brian Kushner, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Severe organ dysfunction, Allergy to GM-CSF, 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: 156 weeks

286 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for individuals with high-risk neuroblastoma, a type of cancer, in complete remission. It combines a vaccine, a sugar called beta-glucan, and a protein that boosts the immune system, known as GM-CSF (Granulocyte-Macrophage Colony Stimulating Factor). The goal is to determine if this combination can strengthen the body's defense against cancer cells. Individuals treated for neuroblastoma and now cancer-free might be suitable candidates, particularly if they have had successful prior immunotherapy. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, prior treatment with other immunotherapy must be completed at least 21 days before the first vaccination, and investigational therapy must be completed at least 28 days before.

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

Research has shown that the treatments tested in this trial have been safe in past studies.

For the vaccine component, OPT-821, studies have examined its use with other vaccines to treat neuroblastoma. These studies primarily focused on determining the right dose and found it to be generally well-tolerated by children.

Beta-glucan, a type of sugar used in this trial, has a strong safety record. One study followed children for over ten years and found it to be safe, with no major side effects.

The third component, GM-CSF, is a protein that boosts the immune system. The FDA approved it in 1991 for other uses, such as aiding recovery after bone marrow transplants. Studies using this protein for neuroblastoma treatment have also found it to be safe.

Overall, previous trials and research suggest these treatments are well-tolerated, with no major safety issues reported. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for neuroblastoma because they utilize a combination of a vaccine, β-glucan, and GM-CSF, offering a novel approach compared to traditional treatments like chemotherapy and radiation. β-glucan, a natural compound, is used to boost the immune system, potentially enhancing the vaccine's effectiveness. Additionally, GM-CSF, a growth factor, is integrated to stimulate white blood cell production, further supporting the body's defense against cancer cells. Unlike conventional therapies, which often have significant side effects, these treatments aim to harness and enhance the body's own immune response to target and fight neuroblastoma more effectively.

What evidence suggests that this trial's treatments could be effective for neuroblastoma?

This trial will evaluate the effectiveness of a vaccine combined with beta-glucan and GM-CSF for treating high-risk neuroblastoma, a type of cancer in children. Participants in Group 1 will receive the vaccine and beta-glucan, while those in Group 2 will receive the vaccine, beta-glucan, and GM-CSF. Research has shown that beta-glucan can strengthen the immune system by preparing certain parts of immune cells, helping the body fight cancer cells more effectively. GM-CSF, a protein that aids in producing more white blood cells, has worked well with other cancer treatments by boosting the immune system. Additionally, a similar vaccine approach demonstrated a one-year survival rate of 93% in patients with comparable high-risk conditions. These findings suggest that this combination treatment could effectively keep neuroblastoma in remission. ^{1 2 3 4 5}

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 confirmed diagnosis, be within certain time frames post-therapy, and have adequate organ function. Pregnant individuals or those with severe allergies to the study drugs, significant organ dysfunction, or life-threatening infections cannot join.

Inclusion Criteria

My neuroblastoma diagnosis is confirmed by lab tests and high urine catecholamine levels.

My neuroblastoma is high-risk based on specific genetic features and its spread.

Prior treatment with other immunotherapy, including mAbs or vaccine, is allowed but must be completed ≥ 21 days before the 1st vaccination. Note: Prior treatment with an investigational therapy must be completed ≥ 28 days before the 1st vaccination. ≥ 21 and ≤ 180 days between completion of systemic therapy and 1st vaccination. Patients have recovered from any toxicities grade 3 or higher caused by prior therapies. Patients with history of allergy to GM-CSF or who are unable to obtain GM-CSF because of insurance issues are eligible but will be assigned to Group 3 (no GM-CSF exploratory arm). Patients previously enrolled on this trial are eligible for repeat enrollment if they did not complete all vaccine injections during the first time on protocol but they will be assigned to Group 3 and will not be included in the primary biostatistical analyses. A negative pregnancy test is required for patients with child-bearing capability. Signed informed consent indicating awareness of the investigational nature of this program

Exclusion Criteria

My major organs are functioning well, without severe issues.

I am currently being treated for a severe infection.

History of allergy to KLH, QS-21, OPT-821, or glucan

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a combination of a bivalent vaccine, oral β-glucan, and GM-CSF (for some groups) with booster vaccinations at specified weeks

156 weeks

Multiple visits for vaccinations and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

32 weeks

What Are the Treatments Tested in This Trial?

Interventions

• GM-CSF
• OPT-821
• β-glucan

Trial Overview The study tests a combination of a bivalent vaccine with β-glucan (a sugar) and GM-CSF (a protein) to boost the immune system against neuroblastoma cancer cells. The treatment aims to improve the body's natural defense by using different mechanisms.

How Is the Trial Designed?

Group I: Group 3 Experimental Treatment 2 Interventions

Group 3 will include participants who cannot be randomized (e.g., due to allergy to GMCSF). It will also include participants previously treated with this vaccine and oral β-glucan on the predecessor MSK protocol IRB# 05-075 or on this protocol (participants can therefore be enrolled more than one time on this protocol). These participants will be treated as in Group 1. Participants who are registered to Group 3 and have been previously treated with vaccine (in this protocol or MSK predecessor 05-075) will not receive vaccines 4 and 6. These patients will receive a total of 8 injections. The analyses in this group will be exploratory.

Group II: Group 2 Experimental Treatment 3 Interventions

Group 2 participants receive oral β-glucan (40 mg/kg/day) starting week 1. Participants also receive GM-CSF (250 mcg/m2/day) x3 days with vaccinations #1-#3; x7 days with vaccinations #4-#9; and x5 days with vaccination #10. The treatment includes annual booster vaccinations, with a 2-week cycle of β-glucan, administered at weeks 8, 20, 32, 52, 78, 104, and 156 (vaccinations #1 \& #4-10)

Group III: Group 1 Experimental Treatment 2 Interventions

Group 1 participants receive oral β-glucan (40 mg/kg/day x 14 days) starting week 1. This schedule includes annual booster vaccinations, with β-glucan, administered at weeks 8, 20, 32, 52, 78, 104, and 156 (vaccinations #1 \& #4-10). Participants will not receive GM-CSF.

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 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]

Cytokine-producing murine neuroblastoma cells (C1300) that were genetically modified to produce IL-2 or GM-CSF showed potential as a tumor vaccine, as they successfully induced protective immunity in mice against unirradiated wild-type neuroblastoma cells.

Irradiated IL-2 or GM-CSF-producing cells maintained their cytokine secretion despite reduced growth, suggesting that these cells can effectively stimulate an immune response without proliferating excessively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor vaccine effect of irradiated murine neuroblastoma cells producing interleukin-2 or granulocyte macrophage-colony stimulating factor. Yoshida, H., Enomoto, H., Kawamura, K., et al.[2019]

The study evaluated hu14.18-IL2 in 27 pediatric patients with recurrent neuroblastoma and found it can be safely administered at a maximum tolerated dose of 12 mg/m2/d, with reversible toxicities similar to those seen in adult studies.

While no complete or partial responses were observed, treatment led to immune activation, indicating potential antitumor activity, and a phase II trial is planned to further assess its efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I clinical trial of the hu14.18-IL2 (EMD 273063) as a treatment for children with refractory or recurrent neuroblastoma and melanoma: a study of the Children's Oncology Group. Osenga, KL., Hank, JA., Albertini, MR., et al.[2021]

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]

A combination of an irradiated tumor vaccine and a continuous localized infusion of 10 ng/d GM-CSF significantly reduced tumor growth rates and prolonged survival times in mice with neuroblastoma, indicating a strong antitumor effect.

The treatment led to notable immune responses, with increased infiltration of CD4+ and CD8+ T cells in the tumor, suggesting that this approach could effectively enhance the body's immune response against neuroblastoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of irradiated tumor vaccine and continuous localized infusion of granulocyte-macrophage colony-stimulating factor on neuroblastomas in mice. Chen, Y., Lin, SM., Lai, HS., et al.[2019]

The autologous neuroblastoma vaccine modified to secrete interleukin-2 (auto-IL-2) was safely administered to 13 patients, showing good tolerance and generating significant immune responses, including increased infiltration of immune cells at injection sites.

Patients in first remission experienced a median event-free survival of 22 months, with some remaining alive and disease-free, suggesting that auto-IL-2 vaccination may be particularly beneficial for those with minimal residual disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1/2 study of autologous neuroblastoma tumor cells genetically modified to secrete IL-2 in patients with high-risk neuroblastoma. Russell, HV., Strother, D., Mei, Z., et al.[2018]

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]

Citations

1. partnertx.com partnertx.com/comprehensive-review-highlights-importance-of-leukine-in-combination-with-anti-gd2-immunotherapy-for-treatment-of-high-risk-pediatric-neuroblastoma/

Comprehensive Review Highlights Importance of Leukine ... The review provides a succinct summary of the mechanistic rationale and clinical data supporting the use of Leukine in combination with anti-GD2 mAbs.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8416151/

Sargramostim (rhu GM-CSF) as Cancer Therapy (Systematic ... Sargramostim [recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF)] was approved by US FDA in 1991 to accelerate bone marrow recovery ...

3. nature.com nature.com/articles/s41467-025-56619-x

The anti-GD2 monoclonal antibody naxitamab plus GM ... Naxitamab demonstrated clinically meaningful efficacy with manageable safety in patients with residual neuroblastoma in bone/BM.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.TPS10061

Naxitamab and granulocyte macrophage colony ... The objective of this study is to investigate the efficacy and safety of naxitamab plus IT in pts with HR NB with primary refractory disease or first relapse.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT01757626

NCT01757626 | Combination Therapy of Antibody Hu3F8 ... The purpose of this study is to find out if an antibody called Humanized 3F8 (Hu3F8) combined with granulocyte- macrophage colony stimulating factor (GM-CSF) is ...