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

Trial Summary

What is the purpose of this trial?

The purpose of the study is to explore the combination of a bivalent vaccine, a sugar called beta-glucan (β-glucan), and a protein called granulocyte-macrophage colony stimulating factor (GM-CSF) as an effective treatment for people with high-risk neuroblastoma that is in complete remission. The combination may be effective because the different parts of the treatment work to strengthen the immune system's response against cancer cells in different ways.

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.

What data supports the effectiveness of the treatment Vaccine + β-glucan + GM-CSF for Neuroblastoma?

Research shows that β-glucan, when used with a ganglioside vaccine, can boost the immune response in patients with high-risk neuroblastoma, which is linked to better survival. Additionally, GM-CSF has shown antitumor effects in neuroblastoma treatment in mice, suggesting potential benefits in humans. ^{1 2 3 4 5}

Is the combination of Vaccine, β-glucan, and GM-CSF safe for treating neuroblastoma?

The combination of β-glucan and GM-CSF has been studied for safety in patients with neuroblastoma. In one study, the treatment was generally well tolerated, but some patients experienced severe low platelet counts (thrombocytopenia), which improved with treatment. Overall, the treatment showed potential for safety, but further investigation is needed. ^{2 3 4 5 6}

What makes the Vaccine + β-glucan + GM-CSF treatment unique for neuroblastoma?

This treatment is unique because it combines a vaccine with β-glucan, which enhances the immune response, and GM-CSF, which stimulates white blood cell production, to target neuroblastoma. This approach aims to boost the body's immune system to fight cancer cells more effectively, unlike traditional treatments that primarily focus on directly killing cancer cells. ^{2 3 4 5 7}

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 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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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 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]

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]

References

1. United States 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. [2018]

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

Effect of Oral β-Glucan on Antibody Response to Ganglioside Vaccine in Patients With High-Risk Neuroblastoma: A Phase 2 Randomized Clinical Trial. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Effects of irradiated tumor vaccine and continuous localized infusion of granulocyte-macrophage colony-stimulating factor on neuroblastomas in mice. [2019]

5. 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]

6. United States 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. [2021]

7. Greece pubmed.ncbi.nlm.nih.gov

Antitumor vaccine effect of irradiated murine neuroblastoma cells producing interleukin-2 or granulocyte macrophage-colony stimulating factor. [2019]