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

7 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new treatment for high-risk neuroblastoma using two types of cancer cell vaccines. One vaccine is modified to release proteins that boost the immune system. The goal is to help the body fight cancer more effectively.

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.

What data supports the effectiveness of the combination vaccine treatment for neuroblastoma?

Research shows that using interleukin-2 (IL-2) in combination with other therapies can improve immune responses and survival in patients with high-risk neuroblastoma. Specifically, IL-2 has been shown to enhance the effectiveness of immunotherapy treatments, such as those involving anti-GD2 antibodies, by boosting the body's immune response against cancer cells. ^{1 2 3 4 5}

Is the combination vaccine for neuroblastoma safe for humans?

The combination vaccine for neuroblastoma, which includes components like IL-2, has been shown to be generally safe in humans. Studies have reported that it is well tolerated, with some patients experiencing increased body temperature and requiring less medication when IL-2 is omitted from treatment. ^{2 3 6 7 8}

How is the combination vaccine for neuroblastoma different from other treatments?

This combination vaccine for neuroblastoma is unique because it uses genetically modified tumor cells to produce interleukin-2 (IL-2), which helps stimulate the immune system to attack cancer cells. Unlike traditional treatments, this approach focuses on enhancing the body's immune response to target and destroy neuroblastoma cells. ^{2 4 9 10 11}

Research Team

Andras A. Heczey, MD

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

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

HIV negative

I was diagnosed before turning 21.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

References

1. England 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. [2022]

2. 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]

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

Outcomes Following GD2-Directed Postconsolidation Therapy for Neuroblastoma After Cessation of Random Assignment on ANBL0032: A Report From the Children's Oncology Group. [2023]

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

Immunotherapy of Neuroblastoma: Facts and Hopes. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Enhancing Neuroblastoma Immunotherapies by Engaging iNKT and NK Cells. [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. United States pubmed.ncbi.nlm.nih.gov

Dose finding study for the use of subcutaneous recombinant interleukin-2 to augment natural killer cell numbers in an outpatient setting for stage 4 neuroblastoma after megatherapy and autologous stem-cell reinfusion. [2013]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Impact of IL-2 on Treatment Tolerance in Patients With High-Risk Neuroblastoma Treated With Dinutuximab Beta-Based Immunotherapy. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Immunomodulatory effects of human neuroblastoma cells transduced with a retroviral vector encoding interleukin-2. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Preclinical evaluation of autologous dendritic cells transfected with mRNA or loaded with apoptotic cells for immunotherapy of high-risk neuroblastoma. [2005]

11. China pubmed.ncbi.nlm.nih.gov

Discovery of YB-1 as a new immunological target in neuroblastoma by vaccination in the context of regulatory T cell blockade. [2019]