GVAX + Checkpoint Inhibitors for Neuroblastoma

No longer recruiting at 1 trial location

Overseen By Natalie B Collins, MD, PHD

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Dana-Farber Cancer Institute

Must not be taking: Systemic corticosteroids, Antiretrovirals

Disqualifiers: Brain metastases, Immunodeficiency, Autoimmune, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for high-risk neuroblastoma, a type of cancer that mainly affects children. It combines a special vaccine called GVAX, made from a patient's own tumor cells, with two drugs, nivolumab (Opdivo) and ipilimumab (Yervoy), to determine if they can work together to help the immune system fight the cancer. The trial targets patients with neuroblastoma that has returned after treatment or hasn't fully responded to standard therapies. Participants should have high-risk neuroblastoma and either residual disease after standard treatment or a relapsed condition. 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 have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on systemic corticosteroid therapy or any other investigational agents. It's best to discuss your specific medications with the trial team.

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

Research shows that the GVAX vaccine, a type of cancer vaccine, is generally well-tolerated. Common side effects include chills (experienced by 54.1% of people), fever (29.3%), headache (16%), and flu-like symptoms (9.8%). These typically occur within a day or two after vaccination.

For nivolumab, studies have found that serious side effects like lung inflammation (pneumonitis) occurred in less than 1% of patients. Although rare, these events can be serious.

Ipilimumab, another drug in the trial, causes side effects in children similar to those in adults, meaning that the side effects seen in adults can also occur in younger patients.

As this is an early-phase trial, the main goal is to ensure the treatment's safety and determine the right dose. This phase can involve some risk, as the treatments are still under study. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about GVAX combined with checkpoint inhibitors for neuroblastoma because it offers a novel approach to tackling this aggressive cancer. Unlike traditional treatments like chemotherapy and radiation, which broadly attack cancer cells, GVAX is a vaccine made from the patient's own tumor cells, aiming to stimulate the immune system to specifically target cancer cells. Additionally, when combined with checkpoint inhibitors like nivolumab and ipilimumab, which help the immune system recognize and attack tumors more effectively, this combination has the potential to enhance the body's natural defenses against cancer. This personalized and targeted strategy represents a significant shift from conventional therapies, promising more precise and potentially less toxic treatment options.

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

In this trial, participants with relapsed or refractory high-risk neuroblastoma will receive a combination of the GVAX vaccine, nivolumab, and ipilimumab. Studies have shown that the GVAX vaccine, when combined with other treatments, can extend the lives of neuroblastoma patients. Research indicates that adding immunotherapy increases the chance of being cancer-free for two years to 66%, compared to 46% without it. Nivolumab has shown promise, with a 50% positive response rate in children with cancers that have many mutations. Additionally, studies on ipilimumab in children have shown some potential, although its effectiveness remains unproven. Together, these treatments aim to boost the immune system to better fight neuroblastoma. ^{1 2 3 5 6}

Who Is on the Research Team?

Natalie B. Collins, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for children over 1 year old with high-risk neuroblastoma, who can undergo surgery at Boston Children's Hospital. They must have recovered from previous cancer treatments and meet specific blood, liver, kidney, and lung function criteria. Pregnant women are excluded, as well as those with certain immune conditions or recent steroid therapy.

Inclusion Criteria

I, or my guardian, can understand and sign the consent form.

I can do most activities but need help with some.

ANC >/= 500/µL

Exclusion Criteria

I am not on high-dose steroids, except for adrenal insufficiency or as premedication.

History of allergic reactions attributed to compounds of similar chemical or biologic composition to GM-CSF or DMSO.

I do not have any serious illnesses that are not under control.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Tissue Collection and Vaccine Preparation

Participants undergo neuroblastoma cell collection from resected tumor tissue to create the GVAX vaccine

3-4 weeks

Treatment

Participants receive the GVAX vaccine along with nivolumab and ipilimumab. Vaccine injected weekly over initial 21-day cycle, biweekly for cycles 2-4, and cycles 5 and subsequent of 28-day cycle duration until vaccine supply is exhausted. Intravenous infusion of nivolumab and ipilimumab every 3 weeks for cycles 1-4, and nivolumab biweekly for cycle 5 and subsequent.

Up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• GVAX Vaccine
• Ipilimumab
• Nivolumab

Trial Overview The study tests a vaccine called GVAX made from the patient's own tumor cells combined with nivolumab and ipilimumab immunotherapies. It aims to treat neuroblastoma by helping the body's immune system recognize and fight cancer cells.

How Is the Trial Designed?

Group I: Relapsed or Refractory High Risk Neuroblastoma Experimental Treatment 4 Interventions

Tissue Collection of Cancerous cells during primary or clinically indicated surgical resection. Manufacture and cryopreservation of vaccine. Treatment with vaccine, nivolumab and ipilimumab. * Vaccine injected weekly over initial 21 day cycle, biweekly for cycles 2-4 of 21 day cycle duration and cycles 5 and subsequent of 28 day cycle duration until vaccine supply is exhausted. * Intravenous infusion of nivolumab every 3 weeks, for cycles 1-4. Cycles 1-4 are 21 days * Intravenous infusion of ipilimumab every 3 weeks, for cycles 1-4. Cycles 1-4 are 21 days * Intravenous infusion of nivolumab biweekly for cycle 5 and subsequent of 28 day cycle duration. Subsequent 28 day cycles will last up to 2 years.

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04239040

GVAX Plus Checkpoint Blockade in Neuroblastoma This research clinical trial is studying the creation and administration of GVAX, an irradiated GM-CSF secreting, autologous neuroblastoma cell vaccine ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8818321/

Immunotherapy approaches targeting neuroblastoma - PMC The addition of immunotherapy to the maintenance phase significantly lengthened the 2-year EFS (66±5% vs. 46±5%) and OS (86±4% vs. 75±5%) of study participants ...

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

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

4. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/imed.1025

Whole tumor cell vaccines engineered to secrete GM‐CSF ... In this single-arm trial, median disease-free survival was 17 months and OS 24 months. Post-GVAX induction of mesothelin-specific CD8+ T cells ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12239805/

Updates on cancer vaccines in brain cancer - PubMed Central The promising developments for neuroblastoma treatment emerge from mRNA COVID-19 vaccine research and brain cancer vaccine clinical trials.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6798079/

Safety and Efficacy of Therapeutic Cancer Vaccines Alone or ... Common adverse events (AEs) included chills (54.1%), pyrexia (29.3%), headache (16%), and influenza-like illness (9.8%), primarily occurring within 1 to 2 days ...