Tumor Cell Vaccine + Cytoxan for Neuroblastoma

(ATOMIC Trial)

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Baylor College of Medicine

Must be taking: Metronomic chemotherapy

Must not be taking: Investigational agents

Disqualifiers: Pregnancy, HIV, Severe infection, others

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

Compensation: Varies

Number of Visits: 9

Duration: 30 weeks

11 Participants Needed

Trial Summary

What is the purpose of this trial?

Neuroblastoma is the second most common solid tumor seen in children, but causes approximately 15% of childhood cancer deaths each year. Patients with high-risk disease require treatment with a combination of chemotherapy, surgery, radiation, and stem cell transplant; however, many will have their disease come back within 3 years. Due to this high rate of relapse, this study is being done to investigate an experimental treatment option for children whose disease has returned. This clinical trial is for patients with neuroblastoma that has either come back after treatment or never went away in the first place. A series of immunizations will be administered using a tumor vaccine and add low-dose chemotherapy to be taken by mouth on a daily basis. The hope is that the vaccine will cause the immune system to recognize and kill more types of neuroblastoma tumors. Additionally, the immunizations will be combined with daily low dose chemotherapy. Daily low-dose chemotherapy, also know as metronomic chemotherapy, works by attacking the blood vessels that allow tumors to grow. Using metronomic doses of a drug called cytoxan can also decrease T regulatory cells, a specific type of cell that tumors use to hide from the immune system. The purpose of this study is to test the safety and anti-tumor effect of the tumor cell vaccination plus low dose, metronomic chemotherapy in treating patients with relapsed/refractory neuroblastoma.

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, you cannot participate if you are currently receiving any investigational agents or have used oral cytoxan for more than 2 consecutive months within the last 6 months.

What data supports the effectiveness of the treatment Tumor Cell Vaccine + Cytoxan for Neuroblastoma?

Research shows that using low-dose cyclophosphamide (a component of Cytoxan) in combination with other immunotherapies can improve survival and control tumor growth in neuroblastoma, a type of cancer. This suggests that the treatment may help the body's immune system fight the cancer more effectively. ^{1 2 3 4 5}

Is the Tumor Cell Vaccine + Cytoxan treatment generally safe for humans?

The Tumor Cell Vaccine, when used with Cytoxan (also known as Cyclophosphamide), has been studied in various forms and is generally considered safe in humans. In a study, a similar vaccine was well tolerated by patients with neuroblastoma, showing that it can be safely administered and can generate immune responses without severe side effects. ^{1 4 6 7 8}

How is the Tumor Cell Vaccine + Cytoxan treatment for neuroblastoma different from other treatments?

This treatment combines a tumor cell vaccine with Cytoxan (a drug that modifies the immune system) to target neuroblastoma cells, which are not commonly found in normal cells, making them ideal targets for immunotherapy. Unlike standard chemotherapy, this approach aims to enhance the body's immune response to fight the cancer, potentially improving survival and making tumors easier to remove surgically. ^{1 2 3 4 7}

Research Team

Andras A. Heczey, MD

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

This trial is for children under 21 with high-risk neuroblastoma that's relapsed or didn't respond to treatment. They must have a certain level of physical function, blood counts, liver and kidney function, not be pregnant or breastfeeding, and able to follow the study plan. Those who've had certain recent treatments or have severe infections, heart issues, HIV, or psychiatric conditions can't join.

Inclusion Criteria

I am able to live with some level of independence.

My neuroblastoma is high risk and has either come back, didn't respond to treatment, or I couldn't complete standard therapy.

I was diagnosed before turning 21.

Exclusion Criteria

I am HIV positive.

Due to the unknown effects of this therapy on a fetus, pregnant women will be excluded from this research

Women who are breast-feeding

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive a series of 8 vaccinations with oral metronomic Cytoxan over approximately 30 weeks

30 weeks

8 visits (in-person) for vaccinations

Follow-up

Participants are monitored for safety and effectiveness after treatment, with evaluations and blood tests

15 years

Regular visits (frequency not specified)

Treatment Details

Interventions

• Cytoxan
• Neuroblastoma Vaccine

Trial Overview The trial tests a new approach combining a neuroblastoma vaccine (with unmodified SKNLP cells and gene-modified SJNB-JF-IL2/SJNB-JF-LTN cells) with daily low-dose oral Cytoxan chemotherapy. The goal is to boost the immune system's ability to fight cancer by reducing tumor-protecting cells and attacking tumor blood vessels.

Participant Groups

Group I: Treatment Plan Experimental Treatment 2 Interventions

Neuroblastoma Vaccine (unmodified SKNLP, with gene-modified SJNB-JF-IL2 and SJNB-JF-LTN neuroblastoma cells) and Cytoxan (Cyclophosphamide)

Cytoxan is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Cyclophosphamide for:

• Breast cancer
• Ovarian cancer
• Leukemia
• Lymphoma
• Multiple myeloma

Approved in United States as Cytoxan for:

• Leukemia
• Lymphoma
• Multiple myeloma
• Ovarian cancer
• Breast cancer
• Neuroblastoma

Approved in Canada as Cyclophosphamide for:

• Leukemia
• Lymphoma
• Multiple myeloma
• Ovarian cancer
• Breast cancer

Approved in Japan as Cyclophosphamide for:

• Leukemia
• Lymphoma
• Multiple myeloma
• Ovarian cancer

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

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]

References

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

Enhanced resection and improved survival in murine neuroblastoma (C1300-NB) after preoperative immunotherapy. [2020]

2. 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]

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

Postoperative immunotherapy of murine C1300-neuroblastoma. [2019]

4. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Cellular immunotherapy for neuroblastoma: a review of current vaccine and adoptive T cell therapeutics. [2021]

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

Combined preoperative and postoperative immunotherapy for murine C1300 neuroblastoma. [2021]

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

Ex vivo activation of CD56(+) immune cells that eradicate neuroblastoma. [2017]

7. 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]

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

Chemoimmunotherapeutic effect of combined treatment with ex vivo generated antigen-presenting immune cells and conventional antitumor agents in a mouse neuroblastoma model. [2018]