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

Trial Summary

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.

What data supports the effectiveness of the DC/AML Vaccine + Decitabine treatment for AML?

Research shows that dendritic cell vaccines, like the DC/AML vaccine, can help the immune system fight leukemia by increasing specific immune responses in patients with AML. Additionally, a study found that a similar dendritic cell vaccine was well tolerated and led to encouraging long-term survival rates in AML patients. ^{1 2 3 4 5}

Is the DC/AML Vaccine + Decitabine treatment generally safe for humans?

Research on dendritic cell vaccines for acute myeloid leukemia (AML) shows that they are generally well tolerated, with no severe adverse side effects reported in several studies. Patients experienced mild and temporary reactions at the injection site, and the treatment was considered safe in both younger and older AML patients. ^{1 3 6 7 8}

How is the DC/AML Vaccine + Decitabine treatment different from other treatments for AML?

The DC/AML Vaccine + Decitabine treatment is unique because it combines a dendritic cell-based vaccine, which uses the patient's own immune cells to target leukemia, with Decitabine, a drug that modifies DNA to enhance immune response. This approach aims to improve the immune system's ability to recognize and attack leukemia cells, offering a novel strategy compared to traditional chemotherapy. ^{2 3 9 10 11}

What is the purpose of this trial?

This research study is studying a cancer vaccine called Dendritic Cell/AML Fusion vaccine (DC/AML vaccine) as a possible treatment for Acute Myelogenous Leukemia (AML). The interventions involved in this study are: * Dendritic Cell/AML Fusion vaccine (DC/AML vaccine) * Decitabine, a chemotherapy drug

Research Team

Jacalyn Rosenblatt, MD

Principal Investigator

Beth Israel Deaconess Medical Center

Eligibility Criteria

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.

Donor chimerism of bone marrow >60%

Exclusion Criteria

My leukemia has spread to my brain or spinal cord.

Pregnant patients

Patients with a known history of HIV

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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-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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

WT1 and PRAME RNA-loaded dendritic cell vaccine as maintenance therapy in de novo AML after intensive induction chemotherapy. [2023]

2. Italy pubmed.ncbi.nlm.nih.gov

Leukemia-derived dendritic cells: towards clinical vaccination protocols in acute myeloid leukemia. [2007]

3. Greece pubmed.ncbi.nlm.nih.gov

Immunotherapy for patients with acute myeloid leukemia using autologous dendritic cells generated from leukemic blasts. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Dendritic cell vaccination in acute myeloid leukemia. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Fusion hybrids of dendritic cells and autologous myeloid blasts as a potential cellular vaccine for acute myeloid leukaemia. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

A phase I/II feasibility vaccine study by autologous leukemic apoptotic corpse-pulsed dendritic cells for elderly AML patients. [2022]

7. United States 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. [2008]

8. Switzerland pubmed.ncbi.nlm.nih.gov

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

9. Australia pubmed.ncbi.nlm.nih.gov

Conjugation of TLR7 Agonist Combined with Demethylation Treatment Improves Whole-Cell Tumor Vaccine Potency in Acute Myeloid Leukemia. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Dendritic cell vaccine therapy for acute myeloid leukemia: questions and answers. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Research progress on dendritic cell vaccines in cancer immunotherapy. [2023]