Dendritic Cell Vaccine + Immunotherapy for Brain Tumor

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Jonsson Comprehensive Cancer Center

Must not be taking: Anti-PD-1, Anti-PD-L1

Disqualifiers: Age, Pregnancy, Autoimmune, Infection, others

Compensation: Varies

Number of Visits: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for diffuse hemispheric glioma, a type of brain tumor that has recurred or worsened. The study tests a vaccine made from the patient's own white blood cells, known as the Dendritic Cell Tumor Peptide Vaccine, combined with immunotherapy drugs to help the immune system fight the tumor. Several groups in the trial receive different combinations of the vaccine, immunotherapy, or a placebo to determine which works best. The trial seeks participants diagnosed with this specific type of brain tumor who plan to undergo surgery to remove it. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this innovative therapy.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, there are specific time intervals required since your last treatments, such as chemotherapy or radiotherapy, before you can enroll. It's best to discuss your current medications with the trial team to get a clear answer.

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

Research has shown that dendritic cell vaccines may help treat brain tumors, with patients living longer and experiencing manageable side effects. Some studies suggest these vaccines are generally safe for humans.

Ipilimumab has been studied and found safe for patients with advanced cancers, including those with brain metastases. Most side effects can be managed, and it has proven effective in other treatments.

Nivolumab has also been researched for safety in brain tumor patients. Studies indicate it can reach brain tumors and assist the immune system in fighting them. While side effects occur, they are similar to those of other immunotherapy drugs and are often manageable.

Overall, previous studies have demonstrated the safety of these treatments, and their use in this trial is based on promising results. However, as this trial is in an early phase, it aims to further understand their safety and effectiveness when used together. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for brain tumors because they offer a fresh approach by combining immunotherapy with a dendritic cell vaccine. Unlike traditional therapies like surgery, chemotherapy, or radiation, which directly target the tumor, these treatments harness the body's immune system to fight cancer. The dendritic cell tumor peptide vaccine works by presenting tumor antigens to the immune system, essentially teaching it to recognize and attack cancer cells. Meanwhile, drugs like Ipilimumab and Nivolumab block certain pathways, enhancing the immune response against the tumor. This innovative strategy aims to improve the body's natural ability to combat brain tumors, potentially leading to better outcomes for patients.

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

Research has shown that dendritic cell vaccines, one of the treatments in this trial, can significantly enhance the immune system's ability to combat brain tumors. Patients receiving this vaccine tend to live longer; one study found an average survival of 455 days compared to 257 days for those who did not receive the vaccine. Nivolumab, another treatment option in this trial, can penetrate brain tumors and boost the body's T-cells, which are crucial for attacking cancer cells. Although some studies have not demonstrated a significant increase in survival with nivolumab alone, it still strengthens the immune system. Ipilimumab, also under study in this trial, is used to enhance the immune response and can sometimes extend the lives of patients with brain tumors. Together, these treatments in the various arms of this trial aim to help the body better target and fight cancer. ^{1 6 7 8 9}

Who Is on the Research Team?

Anthony C. Wang

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for people aged 13-60 with a specific brain tumor (Diffuse Hemispheric Glioma, H3 G34-mutant) that's returned or worsened. They must be scheduled for tumor removal surgery and have good organ function. Women of childbearing age need a negative pregnancy test and must use birth control. Participants can't join if they've had certain recent treatments, live vaccines, other cancers within 3 years, severe allergies to the study drugs, active infections or autoimmune diseases.

Inclusion Criteria

The participant (or legally acceptable representative if applicable) provides informed consent (and written assent from minors) for the trial

I have undergone HLA testing.

It has been over 23 days since my last chemotherapy session.

Exclusion Criteria

Has severe hypersensitivity (>= grade 3) to nivolumab or ipilimumab, and/or any of its excipients

I haven't needed systemic treatment for an autoimmune disease in the last 2 years.

I am younger than 13 or older than 60.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Surgical Treatment

Patients undergo leukapheresis and receive either ppDC, placebo, or nivolumab and ipilimumab prior to surgical resection

10 days

1 visit (in-person)

Post-Surgical Treatment

Patients receive ppDC, placebo, or nivolumab and ipilimumab post-surgical resection, with treatment cycles every 2 weeks for up to 3 cycles

6 weeks

3 visits (in-person)

Long-term Follow-up

Post-treatment, patients may receive nivolumab every 4 weeks for up to 24 months, followed by follow-up visits at 30 days, 6 months, and every 6 months for up to 2 years

Up to 2 years

Regular visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Dendritic Cell Tumor Peptide Vaccine
• Ipilimumab
• Nivolumab

Trial Overview The trial tests a personalized vaccine made from patients' white blood cells combined with immunotherapy drugs nivolumab and ipilimumab against this aggressive brain tumor. The treatment aims to boost the immune system's response to fight cancer cells more effectively. This approach follows surgical resection of the tumor.

How Is the Trial Designed?

Group I: Cohort II Arm C (ppDC, nivolumab) Experimental Treatment 3 Interventions

Within 30 days of surgical resection, patients receive ppDC ID in both arms with poly ICLC IM and nivolumab IV on day 1 of each cycle. Treatment repeats every 2 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Post-treatment, patients may receive nivolumab IV on day 1 of each cycle. Cycles repeat every 4 weeks for up to 24 months following surgical resection in the absence of disease progression or unacceptable toxicity.

Group II: Cohort II Arm A (ppDC, placebo) Experimental Treatment 3 Interventions

Within 30 days of surgical resection, patients receive ppDC ID in both arms with poly ICLC IM and placebo IV on day 1 of each cycle. Treatment repeats every 2 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Post-treatment, patients may receive nivolumab IV on day 1 of each cycle. Cycles repeat every 4 weeks for up to 24 months following surgical resection in the absence of disease progression or unacceptable toxicity.

Group III: Cohort I Arm C (ppDC, nivolumab, ipilimumab) Experimental Treatment 6 Interventions

Patients undergo leukapheresis 10 days prior to first injection. Patients receive ppDC ID divided in both arms with poly ICLC IM on day -10 and nivolumab IV and ipilimumab IV on day -9 prior to standard of care surgical resection.

Group IV: Cohort I Arm B (placebo, nivolumab, ipilimumab) Placebo Group 6 Interventions

Patients undergo leukapheresis 10 days prior to first injection. Patients receive placebo ID in both arms with poly ICLC IM on day -10 and nivolumab IV and ipilimumab IV on day -9 prior to standard of care surgical resection.

Group V: Cohort I Arm A (ppDC, placebo) Placebo Group 5 Interventions

Patients undergo leukapheresis 10 days prior to first injection. Patients receive ppDC ID in both arms with poly ICLC IM on day -10 and placebo IV on day -9 prior to standard of care surgical resection.

Group VI: Cohort II Arm B (placebo, nivolumab) Placebo Group 3 Interventions

Within 30 days of surgical resection, patients receive placebo ID in both arms with poly ICLC IM and nivolumab IV on day 1 of each cycle. Treatment repeats every 2 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Post-treatment, patients may receive nivolumab IV on day 1 of each cycle. Cycles repeat every 4 weeks for up to 24 months following surgical resection in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials

373

Recruited

35,200+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8592940/

Dendritic Cell Vaccination of Glioblastoma: Road to Success ... Dendritic cell vaccination (DCV) is an active immunotherapy that aims at inducing an antitumoral immune response.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2810429/

Dendritic Cell Vaccines for Brain Tumors - PMC Patients receiving DC vaccination were found to have an increased median survival (455 days) compared to that of those in the control group (257 days). Kikuchi ...

3. academic.oup.com academic.oup.com/neuro-oncology/article/26/Supplement_8/viii39/7890417

BIOS-05. PEPTIDE-BASED VACCINES VERSUS DENDRITIC ... Based on current evidence, DCV vaccines perform better than peptide-based vaccines in reducing mortality in GBM patients.

4. molecularbrain.biomedcentral.com molecularbrain.biomedcentral.com/articles/10.1186/s13041-025-01221-x

Recent developments in peptide vaccines against ... A study found that a patient treated with an H3K27M peptide vaccine achieved complete remission. The vaccine activates the immune system by ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0753332225000526

The power of dendritic cell-based vaccines in immunotherapy This review offers a comprehensive analysis of the present-day progress in dendritic cell (DC)-based vaccines and recent efforts to enhance their efficacy.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6204866/

Efficacy and safety analysis on dendritic cell-based vaccine ... DC vaccine can significantly improve OS and PFS, with acceptable toxicity, of HGG patients. Nevertheless, further studies are needed to verify this conclusion.

7. sciencedirect.com sciencedirect.com/science/article/pii/S1471491424001679

Vaccine-based immunotherapy and related preclinical ... This review discusses tumor vaccines against glioma, preclinical models in immunological research, and the role of CD4 + T cells in vaccine-induced antitumor ...

8. jitc.bmj.com jitc.bmj.com/content/2/1/4

Vaccination with dendritic cells loaded with allogeneic ... Conclusion This first-in-human study shows that the GBM6-AD/DC vaccine was well tolerated and was associated with an immune response in a subset ...

9. trials.braintumor.org trials.braintumor.org/trials/NCT04968366

Safety & Efficacy of DC Vaccine and TMZ for the Treatment of ... This is a single-center, single-arm phase I study to determine the safety and preliminary efficacy of autologous dendritic cells (DCs) loaded with multiple ...