Iadademstat + Venetoclax + Azacitidine for Acute Myeloid Leukemia

Recruiting at 4 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Antidepressants, Strong CYP3A inhibitors

Disqualifiers: Intensive chemotherapy, CNS involvement, others

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

Compensation: Varies

Number of Visits: 3

45 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and optimal dosage of a new drug combination—iadademstat (an experimental treatment), azacitidine, and venetoclax—for treating individuals with acute myeloid leukemia (AML) who have not yet received treatment. The goal is to determine if this combination can effectively stop or slow the growth of cancer cells. Individuals with a confirmed AML diagnosis, who have not tried other treatments (except certain specified ones), might be suitable for this study. 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 combination therapy.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot take drugs that target the 5HT2B receptor or the sigma nonspecific receptor, except if they are essential and monitored. You also cannot use strong CYP3A inhibitors, except for certain antifungals with dose adjustments. It's best to discuss your current medications with the trial team.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does mention that you should not use certain drugs that target specific receptors, like some antidepressants, unless they are essential for your care. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

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

Studies have shown that combining iadademstat, venetoclax, and azacitidine might be safe and manageable for patients with newly diagnosed acute myeloid leukemia (AML). In a previous study, all patients who received this combination responded positively, suggesting its effectiveness. The safety profile, which describes how the body handles the treatment, was manageable, with most side effects being mild and controllable.

Although this study is in its early stages and aims to determine the best dose, the initial results are promising. It is important to note that this trial focuses on safety and side effects, indicating potential risks remain, but the treatment shows promise. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Iadademstat, Venetoclax, and Azacitidine for treating Acute Myeloid Leukemia (AML) because it brings a novel approach to the table. Iadademstat is a unique feature here, as it works by inhibiting the LSD1 enzyme, which plays a crucial role in cancer cell proliferation. This mechanism is different from the standard treatments like chemotherapy and targeted therapies such as FLT3 inhibitors. Additionally, when combined with Venetoclax, which targets the BCL-2 protein to induce cancer cell death, and Azacitidine, which helps in demethylating DNA to reactivate tumor suppressor genes, the treatment offers a comprehensive attack on the cancer cells. This multi-target approach could potentially improve outcomes for AML patients, making it a promising development in the fight against this aggressive cancer.

What evidence suggests that this treatment might be an effective treatment for acute myeloid leukemia?

This trial will evaluate the combination of iadademstat, azacitidine, and venetoclax for treating acute myeloid leukemia (AML). Research has shown that combining these treatments might be effective. Studies have found that venetoclax with azacitidine can help AML patients live longer. When used with azacitidine, iadademstat has shown safety and effectiveness as a first treatment for AML. Early results also suggest that iadademstat can help control gene activity in AML. These encouraging findings indicate that this combination therapy could be a promising way to manage AML. ^{1 5 6 7 8}

Who Is on the Research Team?

Annie P Im

Principal Investigator

University of Pittsburgh Cancer Institute LAO

Are You a Good Fit for This Trial?

This trial is for adults over 18 with newly diagnosed Acute Myeloid Leukemia (AML) who haven't started treatment, except possibly hydroxyurea. They should have a white blood cell count below a certain level, be able to swallow pills, weigh at least 50 kg, and have normal liver and kidney function tests.

Inclusion Criteria

My leukemia diagnosis matches the 2022 European standards.

I have AML and haven't been treated, except possibly with hydroxyurea or ATRA.

I can swallow pills.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Patients receive iadademstat, venetoclax, and azacitidine in cycles to determine the recommended phase 2 dose and safety profile

12 weeks

Multiple visits per cycle for drug administration and monitoring

Consolidation

Patients continue to receive iadademstat, venetoclax, and azacitidine in cycles for up to 2 years to maintain remission

Up to 2 years

Regular visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Every 3-4 months

What Are the Treatments Tested in This Trial?

Interventions

• Azacitidine
• Iadademstat
• Venetoclax

Trial Overview The trial is testing the safety and optimal dosage of Iadademstat combined with Azacitidine and Venetoclax in treating AML. These drugs work differently to stop cancer cells from growing by killing them or blocking proteins they need to survive.

How Is the Trial Designed?

Group I: Treatment (iadademstat, venetoclax, azacitidine) Experimental Treatment 6 Interventions

INDUCTION: Patients receive iadademstat PO QD on days 1-5, 8-12, and may also receive it on days 15-19 of each cycle, venetoclax PO QD on days 1-14 or 1-21 of each cycle, and azacitidine IV over 10-40 minutes or SC on days 1-7 of each cycle or days 1-5 and 8-9 after cycle 1. Cycles repeat every 28 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients may also undergo buccal swab collection on study. CONSOLIDATION: Patients receive iadademstat PO QD on days 1-5, 8-12 and may also receive it on days 15-19 of each cycle, venetoclax PO QD on days 1-7 or 1-14 of each cycle, and azacitidine IV over 10-40 minutes or SC on days 1-7 of each cycle or days 1-5 and 8-9 after cycle 1. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection and may undergo bone marrow aspiration throughout the study.

Azacitidine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Vidaza for:

• Acute myeloid leukemia
• Chronic myelomonocytic leukemia
• Myelodysplastic syndromes

Approved in United States as Vidaza for:

• Myelodysplastic syndromes
• Chronic myelomonocytic leukemia

Approved in Canada as Vidaza for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Approved in Japan as Vidaza for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a phase II study involving 60 older or unfit patients with newly diagnosed acute myeloid leukemia (AML), the combination of venetoclax with cladribine and low-dose cytarabine alternating with venetoclax and 5-azacitidine resulted in a high composite complete response rate of 93%.

The treatment showed promising overall survival and disease-free survival rates, with only one death occurring within 4 weeks, indicating that this regimen is effective and has a favorable safety profile for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Study of Venetoclax Added to Cladribine Plus Low-Dose Cytarabine Alternating With 5-Azacitidine in Older Patients With Newly Diagnosed Acute Myeloid Leukemia. Kadia, TM., Reville, PK., Wang, X., et al.[2023]

In a study of 13 patients with acute leukemia treated with venetoclax and azacitidine, 46% developed COVID-19, highlighting a significant risk associated with this treatment during the pandemic.

The study found that 33% of those who contracted COVID-19 died from the virus, indicating that COVID-19 can lead to severe outcomes in patients receiving AZA-VEN therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SARS-CoV-2 Infection in Patients Treated with Azacitidine and Venetoclax for Acute Leukemia: A Report of a Case Series Treated in a Single Institution. Drozd-Sokołowska, J., Mądry, K., Barankiewicz, J., et al.[2023]

In a study of 50 adults with acute myeloid leukemia (AML) in Mexico and Peru, venetoclax-based therapy showed a high complete response rate of 78.6% in newly diagnosed patients and 45.5% in those with relapsed/refractory disease, indicating its efficacy in treating AML.

The median overall survival was 9.6 months for newly diagnosed patients and 8 months for relapsed/refractory patients, suggesting that venetoclax is a viable treatment option even in real-world settings, despite common hematologic toxicities and dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax-based combinations for acute myeloid leukemia: optimizing their use in Latin-America. Gómez-De León, A., Demichelis-Gómez, R., Pinedo-Rodríguez, A., et al.[2022]

In the HiDDAV study involving 42 newly diagnosed AML patients, higher doses of venetoclax (600 mg daily) were found to be tolerable but did not show significant clinical improvement compared to the standard 400 mg dose.

The study revealed that using minimal residual disease (MRD) status to guide the discontinuation of azacitidine did not lead to better outcomes in terms of duration of response or overall survival, suggesting that alternative strategies are needed to optimize treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Higher-dose venetoclax with measurable residual disease-guided azacitidine discontinuation in newly diagnosed acute myeloid leukemia. Gutman, JA., Winters, A., Kent, A., et al.[2023]

In a Japanese subgroup of the phase 3 VIALE-A trial, venetoclax-azacitidine significantly improved overall survival rates compared to placebo-azacitidine, with 67% of patients alive at 12 months versus 46% in the placebo group.

The treatment also resulted in a high complete response (CR) and CR with incomplete hematologic recovery (CRi) rate of 67%, while maintaining a safety profile similar to the global study, indicating it is a viable first-line treatment for Japanese patients with acute myeloid leukemia ineligible for intensive chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax plus azacitidine in Japanese patients with untreated acute myeloid leukemia ineligible for intensive chemotherapy. Yamamoto, K., Shinagawa, A., DiNardo, CD., et al.[2023]

In a phase 1/2 study involving six Japanese patients aged 60 and older with acute myeloid leukaemia, the combination of venetoclax and azacitidine demonstrated a high response rate, with 83% of patients achieving a response, including three complete remissions.

The treatment was generally well tolerated, with a median overall survival of 15.7 months, although some patients experienced serious adverse events, including grade 3 fungal pneumonia, which required treatment adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax in combination with azacitidine in Japanese patients with acute myeloid leukaemia: phase 1 trial findings. Taniguchi, S., Yamauchi, T., Choi, I., et al.[2021]

Outpatient induction therapy using low-dose venetoclax combined with itraconazole and azacitidine is feasible and safe for newly diagnosed acute myeloid leukemia (ND-AML) patients, with 77.7% of participants completing the first treatment cycle as outpatients.

The treatment showed promising efficacy, with a composite complete response rate of 53.9% after the first cycle and 85.7% after the second cycle, indicating that this regimen could be a viable option for patients eligible for intensive chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low dose venetoclax plus itraconazole outpatient induction in newly diagnosed acute myeloid leukemia: A phase 2 study. De la Garza-Salazar, F., Colunga-Pedraza, PR., Gómez-Almaguer, D., et al.[2023]

Citations

1. oryzon.com oryzon.com/en/news-events/news/oryzon-announces-positive-clinical-data-iadademstat-ash-2025

ORYZON announces positive clinical data of iadademstat ... The accepted abstracts highlight encouraging clinical activity and safety data from two ongoing clinical studies evaluating iadademstat-based ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06357182

Study Details | NCT06357182 | Iadademstat in ... Giving iadademstat with azacitidine and venetoclax may be safe, tolerable and/or effective in treating patients with newly diagnosed AML who cannot undergo ...

3. globenewswire.com globenewswire.com/news-release/2025/11/04/3180259/0/en/ORYZON-Announces-Positive-Clinical-Data-of-Iadademstat-at-ASH-2025.html

ORYZON Announces Positive Clinical Data of Iadademstat at "The results to be presented are very promising and underscore iadademstat's potential as a potent and versatile epigenetic modulator in AML, ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2352302624001327

Iadademstat in combination with azacitidine in patients ... The Bcl-2 inhibitor venetoclax, in combination with azacitidine, has improved survival outcomes for a broad spectrum of patients with acute myeloid leukaemia.

5. ashpublications.org ashpublications.org/blood/article/140/Supplement%201/1711/491634/Iadademstat-Combination-with-Azacitidine-Is-a-Safe

Iadademstat Combination with Azacitidine Is a Safe and ... Iadademstat combination with azacitidine is a safe and effective treatment in first line acute myeloid leukemia. Final results of the Alice trial.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06514261

NCT06514261 | Testing the Combination of an Anti-Cancer ... Giving iadademstat with azacitidine and venetoclax may be safe and tolerable in treating patients with treatment naive AML. Detailed Description. PRIMARY ...

7. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-01262

Iadademstat in Combination with Azacitidine and ... Giving iadademstat with azacitidine and venetoclax may be safe, tolerable and/or effective in treating patients with newly diagnosed AML who cannot undergo ...

8. finance.yahoo.com finance.yahoo.com/news/oryzon-announces-positive-clinical-data-130000183.html

ORYZON Announces Positive Clinical Data of Iadademstat ... ... iadademstat with azacitidine and venetoclax in newly diagnosed, unfit AML patients showed a 100% overall response rateUpdated preliminary data ...