Vaccine + Immunological Adjuvant for Neuroblastoma

Overseen By Shakeel Modak, MD

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Allergy to KLH, QS-21, others

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

Compensation: Varies

Number of Visits: 7

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a vaccine designed to help the immune system combat neuroblastoma, a type of cancer often found in children. The vaccine contains two specific proteins that stimulate the body to produce antibodies, which act like soldiers targeting and destroying cancer cells. Participants also take β-glucan to enhance the effectiveness of these antibodies. The trial seeks individuals who have had high-risk neuroblastoma and are currently in remission (the cancer is not active). As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that prior treatment with other immunotherapy is allowed, which might suggest some flexibility. It's best to discuss your specific medications with the trial coordinators.

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

Research has shown that the bivalent vaccine with the OPT-821 adjuvant is generally well-tolerated. In a previous study, researchers tested the highest dose of this vaccine to ensure it did not cause excessive side effects. They carefully determined how much of the treatment could be administered without causing serious problems.

When tested in children, OPT-821, which enhances the vaccine's effectiveness, proved safe at certain doses. Identifying the right dose is crucial for ensuring the treatment's safety. Minor side effects may occur, as with many treatments, but the primary goal is to avoid major issues. This early research provides a solid foundation for understanding the vaccine's safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about these treatments for neuroblastoma because they involve a bivalent vaccine combined with the OPT-821 adjuvant, which stimulates the immune system more effectively than traditional chemotherapy or radiation. Unlike standard treatments that target the cancer cells directly, this approach enhances the body's own immune response to fight the cancer. Additionally, the inclusion of oral β-glucan, a natural compound known to boost immune function, further differentiates this treatment by potentially improving the body's defense mechanisms. This innovative combination aims to provide a more targeted and potentially less harmful alternative to existing therapies.

What evidence suggests that this vaccine might be an effective treatment for neuroblastoma?

Research has shown that a new vaccine containing an ingredient called OPT-821 shows promise in fighting neuroblastoma, a type of cancer. In earlier studies, patients developed antibodies targeting specific proteins on cancer cells, potentially aiding the immune system in attacking and destroying these cells. The vaccine uses two proteins, GD2L and GD3L, primarily found on neuroblastoma cells. These proteins are linked to another protein called KLH and mixed with OPT-821 to enhance the body's immune response. In this trial, participants in different groups will receive the vaccine with varying schedules of oral β-glucan, a sugar included to help white blood cells become more effective at killing cancer cells. Initial findings suggest that this combination might improve the immune system's ability to fight neuroblastoma. ^{1 2 3 4 6}

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 high-risk neuroblastoma patients who've had previous immunotherapy, are in first or subsequent remission, and have normal organ function tests. They must be able to follow the study plan and not have allergies to vaccine components like KLH or OPT-821.

Inclusion Criteria

My neuroblastoma is high-risk and fits specific stage and age criteria.

Signed informed consent indicating awareness of the investigational nature of this program.

I have been diagnosed with neuroblastoma based on tissue tests or bone marrow and urine tests.

Exclusion Criteria

Inability to comply with protocol requirements.

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

I do not have a severe infection that is putting my life at risk.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a total of 7 subcutaneous vaccine injections and oral β-glucan, with variations in the start week for β-glucan between groups

52 weeks

7 visits (in-person) for vaccine administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Bivalent Vaccine with OPT-821 Adjuvant

Trial Overview The trial is testing a bivalent vaccine with two antigens linked to KLH protein, combined with an adjuvant (OPT-821) and oral β-glucan. The goal is to stimulate the immune system to produce antibodies that target neuroblastoma cells.

How Is the Trial Designed?

Group I: vaccine group two Experimental Treatment 2 Interventions

Patients will receive a total of 7 subcutaneous injections, at weeks 1, 2, 3, 8 , 20 , 32 , and 52. Minor schedule adjus tment s are permitted , as needed Vaccines must occur a minimum of 6 days apart. The last three vaccine s can be administered up to one week earlier or later than indicated without representing a protocol violation.Patients assigned to Group 2 will receive oral β glucan (40 mg/kg/day) starting week 1 and continue with approximately 2 weeks on, 2 weeks off, up to 1 cycle after the last vaccination .

Group II: vaccine group three Experimental Treatment 2 Interventions

Patients will receive a total of 7 subcutaneous injections, at weeks 1, 2, 3, 8 , 20 , 32 , and 52. Minor schedule adjus tment s are permitted , as needed Vaccines must occur a minimum of 6 days apart. The last three vaccine s can be administered up to one week earlier or later than indicated without representing a protocol violation.Group 3 will include patients who have previously received vaccine and oral β glucanglucan. Patients in this group will not be randomized using the MSK CRDB system. They will be treated as patients in Group 1 and receive o ral β glucan (40 mg/kg/day) starting at week 6 or 7 and continue with approximately 2 weeks on, 2 weeks off, up to 1 cycle after the last vaccination . They will not be eligible for primary endpoint.

Group III: vaccine group one Experimental Treatment 2 Interventions

Patients will receive a total of 7 subcutaneous injections, at weeks 1, 2, 3, 8 , 20 , 32 , and 52. Minor schedule adjus tment s are permitted , as needed Vaccines must occur a inimum of 6 days apart. The last three vaccine s can be administered up to one week earlier or later than indicated without representing a protocol violation.Patients assigned to in Group 1 will receive o ral β glucan (40 mg/kg/day) starting at week 6 or 7 and continue with approximately 2 weeks on, 2 weeks off, up to 1 cycle after the last vaccination .

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Y-mAbs Therapeutics

Industry Sponsor

Trials

26

Recruited

1,600+

Y-mAbs Therapeutics, Inc

Collaborator

Trials

4

Recruited

490+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/24520094/

Phase I trial of a bivalent gangliosides vaccine in combination ... Results: The study was completed with 15 patients because there was no dose-limiting toxicity at 150 μg/m(2) of OPT-821 (the dosing used in ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT00911560

NCT00911560 | Bivalent Vaccine With Escalating Doses of ... Bivalent Vaccine With Escalating Doses of the Immunological Adjuvant OPT-821, in Combination With Oral β-glucan for High-Risk Neuroblastoma. ClinicalTrials ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5592799/

PHASE I TRIAL OF A BIVALENT GANGLIOSIDES VACCINE ... A phase I trial designed to find the maximally tolerated dose in children of the immunological adjuvant OPT-821 in a vaccine containing neuroblastoma- ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04936529

NCT04936529 | A Study of a Vaccine in Combination With ... 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 ...

5. mskcc.org mskcc.org/cancer-care/clinical-trials/23-198

A Phase 2 Study of a Vaccine in Combination With Beta- ... The people in this study have neuroblastoma that is in remission (no signs of cancer). In addition, their cancers have a strong chance of coming back (high risk) ...

6. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2009-01362

OPT-821 with Vaccine Therapy and Beta-Glucan in ... Giving OPT-821 with vaccine therapy together with beta-glucan may be an effective treatment for high-risk neuroblastoma.