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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for children with neuroblastoma, a cancer that often returns after standard treatments. It combines a tumor vaccine with a daily, low-dose chemotherapy pill called Cytoxan. The goal is to enhance the immune system's ability to recognize and attack neuroblastoma cells, while the chemotherapy cuts off the tumors' blood supply. The trial seeks participants whose neuroblastoma has returned or not responded to previous treatments. 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 therapy.

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.

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

Research has shown that the neuroblastoma vaccine used in this trial has a low rate of side effects, including in children with neuroblastoma, where the vaccine has been well-tolerated. In a small study with a similar vaccine, patients lived longer and demonstrated a good safety record.

Cytoxan, another component of the treatment, is commonly used in cancer therapies and is generally well-tolerated in low doses. It reduces certain cells that help tumors evade the immune system, allowing the immune system to fight the cancer more effectively.

Overall, previous studies have shown both parts of this treatment to be safe. However, since this trial is in the early phase, monitoring for potential side effects remains important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for neuroblastoma, which typically involve chemotherapy, radiation, and surgery, this investigational treatment combines a tumor cell vaccine with Cytoxan (Cyclophosphamide). Researchers are excited about this approach because the neuroblastoma vaccine uses both unmodified and gene-modified neuroblastoma cells to potentially train the immune system to recognize and attack the cancer cells. This unique method aims to enhance the body's natural defenses, providing a more targeted and potentially less toxic treatment option compared to conventional therapies.

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

Studies have shown promising results for the neuroblastoma vaccine, a treatment that participants in this trial may receive. In one study, 4 out of 28 patients experienced significant cancer reduction, with some improvements lasting over four years. Additionally, children with neuroblastoma reported only minor side effects. Research also indicates that Cytoxan, another treatment in this trial, can weaken the tumor's defenses by reducing certain cells that help the tumor evade the immune system. Together, these treatments aim to help the body fight neuroblastoma more effectively. ^{1 6 7 8 9}

Who Is on the Research Team?

Malcolm Brenner, MD

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

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.

I was diagnosed before turning 21.

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

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9463572/

Cyclophosphamide depletes tumor infiltrating T regulatory ... Summary. The outcome for children with high-risk neuroblastoma is poor despite intensive multi-modal treatment protocols.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6796460/

Clinical outcomes and prognostic factors to predict treatment ... The regimen is well tolerated with minimal toxicity among patients with high risk neuroblastoma in Thailand.

3. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1002/pdi3.2512

Metronomic chemotherapy in pediatric neuroblastoma The results showed that maintenance cyclophosphamide was inferior to ASCT, with 3 year EFS rates of 31% and 47%, respectively.

4. siope.eu siope.eu/media/documents/escp-high-risk-neuroblastoma-standard-clinical-practice-recommendations.pdf

escp-high-risk-neuroblastoma-standard-clinical-practice- ... Based on preclinical and early phase trial results showing increased activity when combined with GM-CSF or IL-2, ANBL0032 was a phase III trial designed to test ...

5. nature.com nature.com/articles/s41416-023-02525-2

Phase 1 study of high-dose DFMO, celecoxib ... Patients 2–30 years of age with relapsed/refractory high-risk neuroblastoma received oral DFMO at doses up to 9000 mg/m2/day, with celecoxib ( ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7124978/

Exposure-Toxicity Association of Cyclophosphamide and Its ... Data from 171 patients (0.07–4.9 years) were adequately fitted by a two-compartment (cyclophosphamide) and one-compartment models (metabolites). Young infants ( ...

7. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1002/pbc.32080

Chemo‐Immunotherapy Rescue for High‐Risk ... Objective responses to the combination of chemotherapy and anti-GD2 antibodies have been reported in 35%–49% patients with relapse/refractory ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S2468124525000348

Clinical profile and outcome of children with Neuroblastoma This study describes the clinical and epidemiological profile and outcome of neuroblastoma from a large public hospital in Northern India.

9. ascopubs.org ascopubs.org/doi/10.1200/EDBK_349783

High-Risk and Relapsed Neuroblastoma: Toward More ... Patients treated during this trial had a 97% end-induction response rate and a 73.7% 3-year EFS rate, both of which compare favorably to ...