DC/AML Vaccine + Decitabine for AML

Recruiting at 1 trial location

Overseen By Jacalyn Rosenblatt, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Beth Israel Deaconess Medical Center

Must not be taking: Non-FDA agents, Immunosuppressants

Disqualifiers: HIV, CNS leukemia, Pregnancy, others

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

Compensation: Varies

Number of Visits: 2

Duration: 6 weeks

45 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new cancer vaccine, the DC/AML vaccine, combined with the chemotherapy drug Decitabine, for treating Acute Myelogenous Leukemia (AML). Researchers aim to determine if this combination can improve outcomes for individuals who have already undergone a specific type of stem cell transplant. It suits those who have had an AML cell harvest, received a transplant from a matched or haplo-identical donor, and are now in remission without severe transplant-related issues. This trial might be worth considering if these criteria apply. 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.

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 must not be on any non-FDA approved study agents and should not require active treatment with systemic steroids or immunosuppressive therapy for autoimmune or inflammatory disorders.

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

Research has shown that the DC/AML Fusion vaccine is safe and practical for patients. In one study, researchers successfully created it for 26 out of 27 patients. The vaccine's safety is evident as it did not cause severe side effects, with only minor side effects reported.

The FDA has already approved Decitabine for other uses, indicating it is generally well-tolerated. Studies have demonstrated its effectiveness and manageable side effects for patients with AML, particularly older adults. While some patients might experience side effects, they are usually not severe.

Researchers are testing both treatments together to evaluate their effectiveness in treating AML. Previous studies suggest that both components of the treatment are safe and tolerable for patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard chemotherapy for acute myeloid leukemia (AML), the DC/AML Fusion Vaccine and Decitabine combination is unique because it harnesses the power of the immune system to fight cancer. The DC/AML Fusion Vaccine specifically targets leukemia cells by using dendritic cells fused with AML cells to train the immune system to recognize and attack the cancer. Meanwhile, Decitabine, a hypomethylating agent, works by altering the DNA of cancer cells, potentially making them more susceptible to the immune response triggered by the vaccine. Researchers are excited about this approach because it represents a targeted attack on AML cells, potentially improving outcomes and reducing the risk of relapse compared to traditional treatments.

What evidence suggests that the DC/AML vaccine and Decitabine could be effective for AML?

Research has shown that the Dendritic Cell/AML Fusion vaccine may help treat Acute Myelogenous Leukemia (AML). One study found that 31% of patients who received this vaccine did not see their disease worsen for two years, compared to 23% of those who did not receive the vaccine. This vaccine helps the immune system specifically attack leukemia cells and usually has few side effects. In this trial, some participants will receive the DC/AML Fusion vaccine.

Decitabine, a chemotherapy drug, has improved outcomes for AML patients. In one study, 36.1% of patients responded positively to Decitabine treatment. It is considered effective and relatively safe for AML and other blood disorders. In this trial, other participants will receive Decitabine in combination with the DC/AML Fusion vaccine. Both treatments aim to help patients live longer and improve their quality of life. ^{2 6 7 8 9}

Who Is on the Research Team?

Jacalyn Rosenblatt, MD

Principal Investigator

Beth Israel Deaconess Medical Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with Acute Myelogenous Leukemia (AML) who've had a recent allogeneic transplant. They must be in remission, have good organ function, and not have severe ongoing graft-versus-host disease or other serious illnesses. Participants need to agree to use birth control and can't be on non-FDA approved study drugs or have autoimmune diseases needing steroids.

Inclusion Criteria

I have AML and have had cells stored for future treatment as per specific protocols.

I agree to use birth control during the study.

I do not have severe ongoing graft-versus-host disease.

Exclusion Criteria

My leukemia has spread to my brain or spinal cord.

Pregnant patients

I am currently on steroids or immunosuppressants for an autoimmune or inflammatory condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the DC/AML fusion cell vaccine and decitabine post-transplant

6 weeks

2 vaccines, 3 weeks apart, with potential for a booster

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• DC/AML Fusion Vaccine
• Decitabine

Trial Overview

The trial is testing a cancer vaccine called Dendritic Cell/AML Fusion vaccine alongside Decitabine, a chemotherapy drug. It aims to see if this combination helps AML patients stay in remission after an allogeneic transplant by boosting the body's immune response against leukemia cells.

How Is the Trial Designed?

Group I: AML Patient who are undergoing transplantation Experimental Treatment 1 Intervention

* Patients will be vaccinated with DC/AML fusion cells * Four days of GM-CSF given subcutaneously at the site of vaccination * Patients will receive 2 vaccines, 3 weeks apart, with the potential for a booster vaccine

Group II: AML Patient who are undergoing allogeneic transplantation Experimental Treatment 2 Interventions

* Patients will be vaccinated with DC/AML fusion cells * Four days of GM-CSF given subcutaneously at the site of vaccination * Patients will receive 2 vaccines, 3 weeks apart, with the potential for a booster vaccine * Patients will be treated with 5 days of decitabine in the post-transplant setting

Who Is Running the Clinical Trial?

Beth Israel Deaconess Medical Center

Lead Sponsor

Trials

872

Recruited

12,930,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dana-Farber Cancer Institute

Collaborator

Trials

1,128

Recruited

382,000+

Published Research Related to This Trial

Dendritic cell-based vaccines are a promising strategy for harnessing the immune system to fight acute myeloid leukemia (AML) by inducing targeted immune responses against leukemia-associated antigens.

Current research is focused on optimizing the culture conditions and antigen loading of dendritic cells to enhance their effectiveness, along with exploring the role of natural killer cells and combination therapies to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dendritic cell vaccine therapy for acute myeloid leukemia: questions and answers. Anguille, S., Lion, E., Smits, E., et al.[2019]

Vaccination with autologous dendritic cells (DCs) derived from leukemic blasts in five AML patients was well tolerated, with no severe adverse effects reported, and resulted in stable conditions for three patients lasting 5.5 to 13 months.

The vaccination led to a significant increase in CD8+ T cells that specifically recognized a leukemia-associated antigen, indicating an enhanced immune response against AML, as evidenced by increased granzyme B release and a shift towards a type 1 T helper cell cytokine pattern.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy for patients with acute myeloid leukemia using autologous dendritic cells generated from leukemic blasts. Li, L., Giannopoulos, K., Reinhardt, P., et al.[2023]

Acute myeloid leukemic (AML) blasts can differentiate into leukemic dendritic cells, which may help present leukemic antigens and improve treatment for AML patients with minimal residual disease.

Advancements in culture methods have made it possible to use leukemic dendritic cells in clinical settings, but additional strategies are needed to enhance vaccine effectiveness and address the immune system's tolerance in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Leukemia-derived dendritic cells: towards clinical vaccination protocols in acute myeloid leukemia. Houtenbos, I., Westers, TM., Ossenkoppele, GJ., et al.[2007]

This Phase I/II study tested a vaccine using dendritic cells pulsed with apoptotic leukemic cells in five elderly patients with acute myeloid leukemia (AML), showing no severe adverse events, indicating a good safety profile.

The study suggests that this DC-vaccine approach is feasible and warrants further investigation in larger Phase 2 trials to determine its effectiveness in both older and younger AML patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I/II feasibility vaccine study by autologous leukemic apoptotic corpse-pulsed dendritic cells for elderly AML patients. Chevallier, P., Saiagh, S., Dehame, V., et al.[2022]

Dendritic cells derived from leukemic blasts (AML-DCs) show strong expression of Toll-like receptors (TLR-2 and TLR-4), which can enhance their ability to stimulate immune responses in acute myeloid leukemia patients.

The study found that adding microbial ligands like lipopolysaccharides (LPS) and specific oligodeoxyribonucleotides (ODNs) can potentially boost the effectiveness of AML-DC vaccines by promoting a stronger proinflammatory response, making them promising adjuvants for immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative expression of Toll-like receptor-2, -4, and -9 in dendritic cells generated from blasts of patients with acute myeloid leukemia. Schmitt, A., Li, L., Giannopoulos, K., et al.[2008]

Dendritic cell (DC)-based immunotherapy shows promise as a treatment for elderly patients with acute myeloid leukemia (AML) and high-grade myelodysplastic syndrome (MDS), as these DC can be derived from leukemic cells and enhance antileukemic immunity.

The review discusses the generation of leukemic origin dendritic cells (DCleu) from patients' own leukemic cells, which could lead to personalized immunotherapy options, although further research and clinical trials are needed to validate these approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dendritic Cells of Leukemic Origin: Specialized Antigen-Presenting Cells as Potential Treatment Tools for Patients with Myeloid Leukemia. Amberger, DC., Schmetzer, HM.[2021]

The newly developed tumor vaccine SZU-106-DAC-AML, which combines a TLR-7 agonist with a demethylation agent, significantly enhances the expression of tumor antigens and activates immune responses in both laboratory and animal models.

In a xenograft tumor model, the SZU-106-DAC-AML vaccine demonstrated a strong ability to inhibit tumor growth and improve survival rates, suggesting it could be a promising approach to combat acute myeloid leukemia (AML).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conjugation of TLR7 Agonist Combined with Demethylation Treatment Improves Whole-Cell Tumor Vaccine Potency in Acute Myeloid Leukemia. Zhong, G., Jin, G., Zeng, W., et al.[2023]

Dendritic cell (DC) vaccines have shown promise in treating hematological malignancies like acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) by inducing specific immune responses that can target and eliminate cancer cells.

Recent strategies to enhance the efficacy of DC vaccines include combining them with conventional chemotherapy and immune checkpoint-targeting therapies, indicating a multi-faceted approach to improving cancer treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Research progress on dendritic cell vaccines in cancer immunotherapy. Yu, J., Sun, H., Cao, W., et al.[2023]

In a study involving 20 patients with acute myeloid leukemia (AML) in first complete remission, the autologous dendritic cell vaccine FDC101 was well tolerated, with only mild side effects, and resulted in 55% of patients remaining in remission over a 2-year period.

The five-year overall survival rate was 75%, indicating that this vaccine therapy could be a promising maintenance treatment for AML patients not eligible for stem cell transplantation, especially for older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

WT1 and PRAME RNA-loaded dendritic cell vaccine as maintenance therapy in de novo AML after intensive induction chemotherapy. Fløisand, Y., Remberger, M., Bigalke, I., et al.[2023]

Patients with acute myeloid leukemia (AML), especially those over 65 years old, have a very low 5-year survival rate of only 5.2%, highlighting the urgent need for safer treatment options.

Dendritic cell (DC) vaccines are being explored as a promising immunotherapy for AML, as they play a crucial role in activating the immune system to fight leukemia, potentially offering a less toxic alternative to traditional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dendritic cell vaccination in acute myeloid leukemia. Anguille, S., Willemen, Y., Lion, E., et al.[2021]

In a study involving six patients with acute myeloid leukaemia (AML), tumour cell/dendritic cell fusion hybrids successfully induced anti-leukaemic T-cell responses in three patients, suggesting their potential as a cellular vaccine.

Compared to mature dendritic cells, which induced responses in two patients, the fusion hybrids showed promise in generating immune responses, indicating a novel approach to enhancing anti-leukaemic immunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fusion hybrids of dendritic cells and autologous myeloid blasts as a potential cellular vaccine for acute myeloid leukaemia. Klammer, M., Waterfall, M., Samuel, K., et al.[2020]

Citations

1.

ashpublications.org

ashpublications.org/blood/article/144/Supplement%201/4256/533532/Randomized-Phase-II-Trial-of-Dendritic-Cell-AML

Randomized Phase II Trial of Dendritic Cell/AML Fusion Cell ...

2-year PFS in arm A was 31% by intention to treat and 36% in vaccinated patients (N=22) compared to 23% in arm C (N=13). 2-year OS was 73% in ...

2.

astctjournal.org

astctjournal.org/article/S2666-6367(25)00200-3/fulltext

Final Results of Phase 1 Trial of Dendritic Cell/AML Fusion ...

Fusion vaccine was successfully generated in 26 of 27 patients. One patient relapsed prior to leukapheresis, one had insufficient DCs and 6 patients did not ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03679650

Study Details | NCT03679650 | Dendritic Cell/AML Fusion ...

This research study is studying a cancer vaccine called Dendritic Cell/AML Fusion vaccine (DC/AML vaccine) as a possible treatment for Acute Myelogenous ...

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC5889209/

A blood dendritic cell vaccine for acute myeloid leukemia ...

Dendritic cell (DC) vaccination can generate leukemia-specific autologous immunity with little toxicity. Promising results have been achieved with vaccines ...

5.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0006497123053764

Phase 1 Trial of Dendritic Cell/AML Fusion Cell Vaccine ...

The median yield of DCs was 106x10 6 (range 19-182x10 6) and mean viability 81%. Fusion vaccine was successfully generated in 25 of 26 patients ...

6.

sciencedirect.com

sciencedirect.com/science/article/pii/S2666636725002003

Final Results of Phase 1 Trial of Dendritic Cell/AML Fusion ...

Fusion vaccine was successfully generated in 26 of 27 patients. One patient relapsed prior to leukapheresis, one had insufficient DCs and 6 patients did not ...

7.

ashpublications.org

ashpublications.org/blood/article/138/Supplement%201/2830/481337/Post-Transplant-Vaccination-with-a-Personalized

Post-Transplant Vaccination with a Personalized Dendritic ...

We report the results of a phase 1 clinical trial (NCT03679650) evaluating the use of DC/AML fusion vaccine in patients with acute myeloid ...

8.

ash.confex.com

ash.confex.com/ash/2023/webprogram/Paper190832.html

Phase 1 Trial of Dendritic Cell/AML Fusion Cell Vaccine ...

Vaccination using host-derived leukemia cells and donor derived DC was safe and feasible. Adverse events post vaccination have included ...

9.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03059485

DC/AML Fusion Cell Vaccine vs Observation in Patients ...

In this research study, the investigators are determining if the DC/AML vaccine can be used safely in subjects with acute leukemia after finishing chemotherapy, ...