Dendritic Cell Immunotherapy for Pancreatic Cancer

(DECIST Trial)

Recruiting at 2 trial locations

Overseen By Benjamin Musher

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Diakonos Oncology Corporation

Must not be taking: Systemic steroids, Immunosuppressants

Disqualifiers: Unresectable cancer, HIV, Autoimmune, others

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

Compensation: Varies

Number of Visits: 3

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for pancreatic cancer using dendritic cell (DC) therapy to assess its safety and feasibility. The therapy uses a person's own cells to help the immune system fight cancer after surgery. Participants have pancreatic cancer that can be surgically removed and have already had or will have chemotherapy before and after surgery. Those with frequent issues or severe restrictions due to their condition might be suitable candidates. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on systemic steroids or immunosuppressive agents within 7 days before starting Step 2 of the trial.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that vaccines using dendritic cells, like the one in this trial, could help treat pancreatic cancer. Earlier studies have successfully activated the immune system with this type of treatment without causing serious side effects. For example, one study found that patients did not experience major negative reactions, suggesting the treatment is generally safe. Additionally, the FDA granted a similar vaccine fast-track status for pancreatic cancer, indicating trust in its safety and potential benefits. Although this trial marks the first human test of this vaccine, these early results are encouraging regarding its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Most treatments for pancreatic cancer, like chemotherapy and radiation, aim to kill cancer cells directly. But dendritic cell (DC) immunotherapy works differently by harnessing the body's own immune system. This therapy uses dendritic cells, a type of immune cell, which are loaded with pieces of the patient's tumor and reintroduced into the body to stimulate an immune response against the cancer. Researchers are excited because this personalized approach could potentially offer a more targeted attack on cancer cells with fewer side effects than traditional treatments. Plus, the ability to tailor the treatment to each patient’s specific cancer profile offers a promising new avenue in the fight against this challenging disease.

What evidence suggests that this treatment might be an effective treatment for pancreatic cancer?

Studies have shown that dendritic cell (DC) vaccines can help treat pancreatic cancer. In this trial, participants will receive DC therapy in different cohorts. Research indicates that patients who received DC therapy after surgery and standard treatment had a 2-year recurrence-free survival rate of over 60%. This means many patients did not experience cancer recurrence for at least two years after treatment. The therapy also triggered a specific immune response in patients, suggesting the vaccine might be effective. Additionally, about 65% of patients reported an improved quality of life after receiving this treatment. These early results suggest that DC vaccines could be a promising option for pancreatic cancer. ^{1 6 7 8 9}

Who Is on the Research Team?

Benjamin Musher

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

Adults over 18 with pancreatic adenocarcinoma that's potentially removable and who've finished standard chemo and surgery. They must have good organ function, no HIV, Hepatitis B or C (with exceptions), no autoimmune diseases, not be on steroids/immunosuppressants recently, and agree to contraception if of childbearing potential.

Inclusion Criteria

I am a man who can father children and will use contraception during and for 12 weeks after the study.

I have a type of pancreatic cancer that doctors think can be surgically removed and I'm considered a good candidate for additional chemotherapy.

I have finished all my initial cancer treatments and surgery as recommended.

Exclusion Criteria

I am on a unique chemotherapy plan not typically used.

I am not pregnant, breastfeeding, and if of childbearing age, I have a recent negative pregnancy test.

Any severe or uncontrolled medical condition or other condition that could affect participation in this study (in the opinion of the investigator), including but not limited to: hyper/hypothyroidism, active systemic autoimmune disorders, untreated viral hepatitis or autoimmune hepatitis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Standard Chemotherapy

Participants complete standard chemotherapy for pancreatic adenocarcinoma

Varies

Dendritic Cell Vaccine Treatment

Participants receive 3 doses of dendritic cell vaccine, one every 14 days, with weekly peg-interferon a-2a

6 weeks

3 visits (in-person) for vaccination, weekly visits for peg-interferon

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

Long-term Follow-up

Participants are monitored for recurrence and overall survival

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Autologous DC vaccine

Trial Overview This phase 1 trial tests the safety of a dendritic cell vaccine for pancreatic cancer patients. It involves escalating doses given three times post-standard treatments to see how well patients tolerate it.

How Is the Trial Designed?

Group I: Autologous DC Therapy Group B Cohort 2 Experimental Treatment 1 Intervention

The DC therapy is manufactured from autologous dendritic cells loaded with tumor cell lysate and RNA. Patients will receive 2 doses of DC therapy (separated by 14 days) and be monitored (vital signs every 30 minutes) for 2 hours after each dose. During intervention, patients receive weekly peg-IFN at 180 mcg/week on the first day of administration up through 14 days after last dose. DC Therapy dose evaluated in Group B Cohort 2: First Cycle 1st dose - 12 million cells First Cycle 2nd dose - 12 million cells Second Cycle 1st dose - 12 million cells (optional) Second Cycle 2nd dose - 12 million cells (optional) Patients in Group B cohort 2 will receive the DC therapy after neoadjuvant chemotherapy and surgery (1st cycle), with an option for additional DC therapy (2nd cycle) after adjuvant chemotherapy.

Group II: Autologous DC Therapy Group B Cohort 1 Experimental Treatment 1 Intervention

The DC therapy is manufactured from autologous dendritic cells loaded with tumor cell lysate and RNA. Patients will receive 2 doses of DC therapy (separated by 14 days) and be monitored (vital signs every 30 minutes) for 2 hours after each dose. During intervention, patients receive weekly peg-IFN at 180 mcg/week on the first day of administration up through 14 days after last dose. DC Therapy dose evaluated in Group B Cohort 1: First Cycle 1st dose - 8 million cells First Cycle 2nd dose - 8 million cells Second Cycle 1st dose - 8 million cells (optional) Second Cycle 2nd dose - 8 million cells (optional) Patients in Group B cohort 1 will receive the DC therapy after neoadjuvant chemotherapy and surgery (1st cycle), with an option for additional DC therapy (2nd cycle) after adjuvant chemotherapy.

Group III: Autologous DC Therapy Group A Experimental Treatment 1 Intervention

ENROLLMENT IN THIS ARM HAS BEEN COMPLETED The DC therapy is manufactured from autologous dendritic cells loaded with autologous tumor cell lysate and mRNA. Patients will receive 3 doses of DC therapy (one every 14 days) and be monitored (vital signs every 30 minutes) for 2 hours after each dose. During intervention, patients receive weekly peg-IFN at 180 mcg/week on the first day of administration up through 14 days after last dose. DC Therapy dose evaluated in Group A: 1. st dose - 0.5 million cells 2. nd dose - 1 million cells 3. rd dose - 2 million cells Patients in Group A will receive the DC therapy after neoadjuvant chemotherapy, surgery and adjuvant chemotherapy.

Who Is Running the Clinical Trial?

Diakonos Oncology Corporation

Lead Sponsor

Trials

1

Recruited

140+

Baylor College of Medicine

Collaborator

Trials

1,044

Recruited

6,031,000+

Cancer Cures for Kids

Collaborator

Trials

1

Recruited

40+

Published Research Related to This Trial

The dendritic cell (DC) vaccine modified with tumor lysate and Interleukin-18 (IL-18) significantly enhanced immune responses in a mouse model of pancreatic carcinoma, leading to higher levels of IL-18 and IFN-gamma compared to other treatment groups.

Mice treated with the DC-IL18-Lysate vaccine remained tumor-free for at least 50 days and had a median survival of over 62 days, which was significantly longer than other groups, indicating its potential efficacy as a therapeutic vaccine against pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The immunotherapeutic effect of dendritic cells vaccine modified with interleukin-18 gene and tumor cell lysate on mice with pancreatic carcinoma. Tang, ZH., Qiu, WH., Wu, GS., et al.[2019]

In a study of 7 patients with advanced pancreatic ductal adenocarcinoma (PDA) receiving a WT1-targeting dendritic cell vaccine combined with chemotherapy, those who responded well (super-responders) had significantly lower levels of plasma matrix metalloproteinase-9 and systemic inflammatory markers compared to non-responders.

Lower cytoplasmic expression of WT1 in PDA cells was also associated with better overall survival, suggesting that both low inflammatory responses and low WT1 expression may serve as predictive markers for patient outcomes in this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predicted Markers of Overall Survival in Pancreatic Cancer Patients Receiving Dendritic Cell Vaccinations Targeting WT1. Ito, Z., Kan, S., Bito, T., et al.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38950309/

Dendritic Cell-Based Immunotherapy in Patients With ... This study reached its primary end point of a 2-year RFS rate of ≥60% following pancreatectomy after SOC treatment and adjuvant DC-based ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.02585

Dendritic Cell–Based Immunotherapy in Patients With ... DC therapy was able to induce a vaccine-specific immune response in patients with pancreatic cancer after resection and standard-of-care ...

3. onclive.com onclive.com/view/dendritic-cell-based-immunotherapy-data-in-resected-pancreatic-cancer-published-in-jco

Dendritic Cell–Based Immunotherapy Data in Resected ... MesoPher cell therapy led to a 2-year recurrence-free survival rate of 64% and low-grade AEs in resected pancreatic cancer following chemotherapy.

4. ascopost.com ascopost.com/news/july-2024/resected-pancreatic-cancer-autologous-dendritic-cell-vaccination/

Resected Pancreatic Cancer Autologous Dendritic Cell ... The primary outcome measure was 2-year recurrence-free survival, with a rate of ≥ 60% defined as a clinically meaningful improvement vs ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4727101/

Clinical outcome of immunotherapy with dendritic cell ... In the I group, 61% of the patients developed a positive, delayed-type hypersensitivity response and 65% of the patients exhibited an improvement in QOL. The ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04157127

Study Details | NCT04157127 | Th-1 Dendritic Cell ... This is a phase 1, first in human, dose escalation study for safety and feasibility of multi-dose dendritic cell (DC) therapy for pancreatic ductal ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11029181/

Dendritic cell-based vaccination of patients with advanced ... Median survival was 10.5 months. No severe side effects were observed. Tumor-reactive T cells could be detected prior to vaccination. DC vaccination increased ...

8. 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.

9. targetedonc.com targetedonc.com/view/fda-fast-tracks-novel-dendritic-cell-vaccine-for-pancreatic-cancer

FDA Fast Tracks Novel Dendritic Cell Vaccine for ... A dendritic cell vaccine called DOC1021 shows early promise in treating pancreatic cancer and has received a fast track designation from the FDA.