Combination Vaccine for Neuroblastoma

(CHESAT Trial)

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Baylor College of Medicine

Must not be taking: Investigational agents

Disqualifiers: Pregnant, HIV-positive, Uncontrolled illness, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination vaccine for individuals with high-risk neuroblastoma, a cancer that typically affects young children. Researchers aim to determine the vaccine's safety and effectiveness when combined with chemotherapy and stem cell treatment. The trial will assess two different vaccine doses to identify the best option. Ideal candidates are those with high-risk neuroblastoma planning to undergo a stem cell procedure after chemotherapy. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, giving participants the opportunity to be among the first to receive this new vaccine.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, you cannot be on any investigational agents or have received any tumor vaccines in the past six months.

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

Research has shown that the combination vaccine for neuroblastoma, which includes a component called IL-2, is generally safe. Earlier studies suggest it is well-tolerated, with no serious side effects reported. This vaccine is now being tested with a new component called SKNLP, which has not been studied before.

The trial is in its early stages, focusing primarily on assessing the treatment's safety. This phase typically involves small groups of patients and closely monitors any side effects. Reaching this stage often indicates that earlier tests suggested the treatment might be safe.

Overall, evidence supports the safety of the vaccine's main components, but the combination with SKNLP is still under investigation for safety in this trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for neuroblastoma because they use a combination of innovative components to enhance the immune response against cancer cells. Unlike standard treatments that often involve chemotherapy or radiation, these investigational therapies include SNJB-JF-IL2 and SJNB-JF-Lptn, which are designed to boost the body's natural defenses. Additionally, the treatments explore varying dose levels of SKNLP, potentially optimizing efficacy and minimizing side effects. This approach aims to offer a more targeted attack on neuroblastoma, with the promise of improved outcomes and fewer adverse effects compared to traditional therapies.

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

This trial will evaluate a combination vaccine for high-risk neuroblastoma, with participants receiving either Dose Level 1 or Dose Level 2. The vaccine includes SNJB-JF-IL2, SJNB-JF-Lptn, and SKNLP. Research has shown that such combination vaccines might help treat high-risk neuroblastoma. Early studies suggest that similar vaccines can enhance the body's immune response to fight cancer cells. The SNJB-JF-IL2 component is designed to release substances like IL-2 and lymphotactin, which activate the immune system. This approach aims to improve the immune system's ability to find and destroy neuroblastoma cells. Initial results are promising, but further research is needed to confirm its effectiveness. ^{1 2 3 5 6}

Who Is on the Research Team?

Andras A. Heczey, MD

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

This trial is for individuals under 21 years old with high-risk neuroblastoma, who are about to have stem cell rescue after intense chemotherapy. They must not be pregnant, HIV positive, or have received other vaccines or investigational agents in the past six months. Participants should agree to effective birth control during and for six months post-trial.

Inclusion Criteria

I was diagnosed before turning 21.

HIV negative

My diagnosis was high-risk neuroblastoma.

Exclusion Criteria

I do not have any severe illnesses or social situations that would stop me from following the study's requirements.

I am not currently on experimental drugs or had cancer vaccines in the last 6 months.

Pregnant

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Multiple cycles of induction chemotherapy with harvest of autologous stem cells and local control of the tumor with radiation therapy and/or surgery

Varies per institutional standards

Consolidation

High dose chemotherapy with autologous stem cell rescue (HDT/SCR)

Varies per institutional standards

Maintenance

Treatment with Isotretinoin (Cis-Retinoic Acid, CRA) starting day +90 after HDT/SCR

Varies per institutional standards

Vaccination

Immunization with gene-modified, IL-2/lymphotactin secreting SJNB-JF-IL2 and SJNB-JF-Lptn cells co-administered with the unmodified SKNLP neuroblastoma cell line

Up to 12 vaccinations

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• SNJB-JF-IL2 and SJNB-JF-Lptn + Dose Level 1 SKNLP
• SNJB-JF-IL2 and SJNB-JF-Lptn + Dose Level 2 SKNLP

Trial Overview The study tests the safety and effectiveness of two allogeneic neuroblastoma tumor cell line vaccines combined with IL-2/Lptn secretion on patients with high-risk neuroblastoma undergoing chemotherapy and autologous stem cell rescue as consolidation therapy.

How Is the Trial Designed?

Group I: Dose Level 2 Experimental Treatment 1 Intervention

SNJB-JF-IL2 and SJNB-JF-Lptn + Dose Level 2 SKNLP

Group II: Dose Level 1 Experimental Treatment 1 Intervention

SNJB-JF-IL2 and SJNB-JF-Lptn + Dose Level 1 SKNLP

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

Center for Cell and Gene Therapy, Baylor College of Medicine

Collaborator

Trials

114

Recruited

2,900+

Published Research Related to This Trial

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]

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]

In a phase 3 trial involving 406 children and young people with high-risk neuroblastoma, the addition of subcutaneous IL-2 to dinutuximab beta did not improve event-free survival rates compared to dinutuximab beta alone, with 3-year event-free survival rates of 60% and 56% respectively.

The combination treatment with subcutaneous IL-2 resulted in significantly higher toxicity, leading to a lower treatment completion rate (62% vs. 87% for dinutuximab beta alone), indicating that dinutuximab beta with isotretinoin should remain the standard care for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interleukin 2 with anti-GD2 antibody ch14.18/CHO (dinutuximab beta) in patients with high-risk neuroblastoma (HR-NBL1/SIOPEN): a multicentre, randomised, phase 3 trial. Ladenstein, R., Pötschger, U., Valteau-Couanet, D., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7554151/

Emerging therapeutic targets for neuroblastoma - PMC SNJB-JF-IL2 and SJNB-JF-Lptn + Dose Level 1 SKNLP. Phase 1/2, NCT02173093 ... outcomes in neuroblastoma: a report from the children's oncology group.

2. withpower.com withpower.com/trial/phase-2-neuroblastoma-5-2008-9657b

Combination Vaccine for Neuroblastoma (CHESAT Trial) ... JF-IL2 and SJNB-JF-Lptn + Dose Level 2 SKNLP will have tolerable side effects & efficacy for patients with Neuroblastoma and Neuroblastoma. Learn more about the

3. sciencedirect.com sciencedirect.com/science/article/pii/S2667394022000077

Immunotherapy for neuroblastoma using mRNA vaccines mRNA vaccine is an emerging technology showing immense potential for the precise treatment of high-risk neuroblastoma.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8797508/

Updated Results of a Phase II Study Using hu14.18K322A 18K322A to induction chemotherapy significantly improves early responses in patients with newly diagnosed HR neuroblastoma (66.7% v 39.1%; 95% CI 55.0 to 78.3 v ...

5. researchgate.net researchgate.net/publication/359020992_Immunotherapy_for_neuroblastoma_using_mRNA_vaccines

Immunotherapy for neuroblastoma using mRNA vaccines The characteristics such as elevated effectiveness, harmless administration, quick expansion abilities, and efficient manufacturing allows the ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34871104/

Updated Results of a Phase II Study Using hu14.18K322A Adding hu14.18K322A to induction chemotherapy improved early objective responses, significantly reduced tumor volumes in most patients, ...