Decitabine + Other Drugs for Acute Myeloid Leukemia

Overseen By Tapan Kadia, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: APL, Active CNS disease, Uncontrolled illness, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 96 weeks

125 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the side effects and potential benefits of using decitabine, a chemotherapy drug, alone or with other drugs to treat acute myeloid leukemia (AML) in remission. The trial aims to determine how well these combinations stop cancer cells from growing or spreading. It includes various treatment plans using decitabine with venetoclax, gilteritinib, enasidenib, or ivosidenib. Individuals in remission from AML after intensive or lower-intensity therapy, who are not immediately receiving a stem cell transplant, might be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss your current medications with the trial team to get specific guidance.

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

Research has shown that decitabine and cedazuridine are generally well-tolerated. In one study, serious side effects such as fever and low white blood cell counts occurred in 98% of patients, but the death rate in the first month remained low at 3%.

When combined with venetoclax, studies have found this treatment safe for patients with certain blood conditions, with a safety profile similar to other treatments for challenging cases.

Research suggests that pairing decitabine and cedazuridine with gilteritinib can help maintain remission in leukemia patients, though low blood cell counts are a common side effect.

The combinations of decitabine and cedazuridine with enasidenib or ivosidenib are still under study. Early results indicate these combinations are manageable, but more data is needed to confirm their safety.

These treatments are being tested in early clinical trials, so researchers are closely monitoring safety and side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for acute myeloid leukemia (AML) because they combine decitabine with other innovative drugs to potentially improve outcomes. Unlike traditional chemotherapy, these combinations use targeted therapies like gilteritinib, enasidenib, and ivosidenib, which specifically target genetic mutations found in some AML patients. These targeted approaches could lead to more effective treatments with potentially fewer side effects. Additionally, the combination of decitabine and cedazuridine is designed to enhance the effectiveness of decitabine by improving its absorption when taken orally, offering a more convenient treatment option.

What evidence suggests that this trial's treatments could be effective for acute myeloid leukemia?

Research has shown that taking decitabine and cedazuridine together may help treat acute myeloid leukemia (AML). Studies have found that this combination can lead to a 67% overall response rate, with 40% of patients experiencing complete remission, meaning no signs of cancer. In this trial, participants in different arms will receive various combinations of these drugs.

In Arm A, participants receive decitabine and cedazuridine alone. Arm B includes the addition of venetoclax, which has proven effective and generally safe for older AML patients. Arm C adds gilteritinib for patients with certain gene mutations, showing potential benefits. Arm D involves enasidenib, and Arm E involves ivosidenib, both of which may help block enzymes that cancer cells need to grow, providing extra help in controlling the disease. Each combination aims to stop cancer cells from growing and spreading. ^{1 6 7 8 9}

Who Is on the Research Team?

Tapan Kadia, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Adults aged 18+ with Acute Myeloid Leukemia in remission after intensive or lower intensity therapy, not immediately proceeding to stem cell transplant. Participants must have completed at least one consolidation cycle (intensive) or two cycles (lower intensity), be within certain health parameters, and agree to contraception.

Inclusion Criteria

Platelet count > or = 50 x k/uL

Absolute neutrophil count (ANC) > 0.5 x k/uL

Ability to understand and sign informed consent

Exclusion Criteria

I do not have a history of AML outside the bone marrow, except for controlled CNS involvement.

I have been diagnosed with a specific type of leukemia (APL or AML - M3).

I am willing to leave my current trial to join and receive treatment in a new trial.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive decitabine and cedazuridine alone or in combination with venetoclax, gilteritinib, enasidenib, or ivosidenib. Treatments repeat every 4 weeks for up to 24 cycles.

96 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

6-12 months

What Are the Treatments Tested in This Trial?

Interventions

• Decitabine
• Enasidenib
• Gilteritinib
• Ivosidenib
• Venetoclax

Trial Overview This trial tests decitabine alone or combined with venetoclax, gilteritinib, enasidenib, or ivosidenib as maintenance therapy for AML in remission. It aims to see how these drugs affect cancer cell growth by killing them, stopping division/spread, and blocking proteins/enzymes needed for growth.

How Is the Trial Designed?

Group I: Arm E (decitabine and cedazuridine, ivosidenib) Experimental Treatment 2 Interventions

Patients receive decitabine and cedazuridine PO QD on days 1-3 and ivosidenib PO QD on days 1-28. Treatments repeat every 4 weeks for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

Group II: Arm D (decitabine and cedazuridine, enasidenib) Experimental Treatment 2 Interventions

Patients receive decitabine and cedazuridine PO QD on days 1-3 and enasidenib PO QD on days 1-28. Treatments repeat every 4 weeks for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

Group III: Arm C (decitabine and cedazuridine, gilteritinib) Experimental Treatment 2 Interventions

Patients receive decitabine and cedazuridine PO QD on days 1-3 and gilteritinib PO QD on days 1-28. Treatments repeat every 4 weeks for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

Group IV: Arm B (decitabine and cedazuridine, venetoclax) Experimental Treatment 2 Interventions

Patients receive decitabine and cedazuridine PO QD on days 1-3 and venetoclax PO QD on days 1-5. Treatments repeat every 4 weeks for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

Group V: Arm A (decitabine and cedazuridine) Experimental Treatment 1 Intervention

Patients receive decitabine and cedazuridine PO QD on days 1-3. Treatments repeat every 28 days for up to 4 weeks in the absence of disease progression or unacceptable toxicity.

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

Approved in European Union as Dacogen for:

• Acute myeloid leukemia
• Myelodysplastic syndromes

Approved in United States as Dacogen for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Approved in Canada as Dacogen for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Approved in Japan as Dacogen for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

The fixed-dose oral combination of decitabine and cedazuridine (Inqovi®) has been approved for treating myelodysplastic syndromes (MDS) and chronic myelomonocytic leukaemia (CMML), enhancing the oral bioavailability of decitabine through the inhibition of cytidine deaminase by cedazuridine.

Decitabine is already an established treatment for MDS and CMML, and the combination therapy has shown promise in ongoing clinical studies for other cancers like acute myeloid leukaemia (AML), glioma, and solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decitabine/Cedazuridine: First Approval. Dhillon, S.[2021]

A new low-intensity treatment regimen combining cladribine and low-dose cytarabine alternating with decitabine showed promising results in elderly or unfit patients with acute myeloid leukaemia (AML), with a median disease-free survival of 10.8 months and a median overall survival of 13.8 months based on a study of 118 patients.

The regimen was well tolerated, with only 1% of patients experiencing early death within the first 4 weeks, indicating a favorable safety profile compared to traditional therapies, which often have higher toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cladribine and low-dose cytarabine alternating with decitabine as front-line therapy for elderly patients with acute myeloid leukaemia: a phase 2 single-arm trial. Kadia, TM., Cortes, J., Ravandi, F., et al.[2019]

Decitabine is an effective hypomethylating agent for treating acute myeloid leukemia (AML), significantly improving overall survival and response rates compared to standard care, based on results from the phase 3 DACO-016 trial with adult patients who are not eligible for standard chemotherapy.

The treatment is generally well tolerated and remains effective even in patients with adverse-risk karyotypes or TP53 mutations, making it a valuable option for those unfit for more intensive therapies, with potential for future combination treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Clinical Value of Decitabine Monotherapy in Patients with Acute Myeloid Leukemia. Santini, V., Lübbert, M., Wierzbowska, A., et al.[2022]

Decitabine, administered at a dose of 20 mg/m² for 5 consecutive days, has been approved for older patients (≥65 years) with acute myeloid leukaemia (AML) who cannot undergo standard treatment, showing clinically meaningful improvements in overall survival after extended follow-up.

In a pivotal phase III trial, decitabine demonstrated significantly higher complete remission rates compared to standard treatment options like cytarabine, with a safety profile similar to cytarabine, including common side effects like fever and low blood cell counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decitabine: a review of its use in older patients with acute myeloid leukaemia. Curran, MP.[2021]

Decitabine is a DNA methyltransferase inhibitor with a long history of antileukemic efficacy, particularly effective in treating acute myeloid leukemia in older patients or those unable to undergo intensive therapy.

The current dosing regimen of decitabine (20 mg/m² for 5 days) has been refined to minimize nonhematologic toxicity, making it a promising option for patients who may not tolerate more aggressive treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decitabine for acute myeloid leukemia. Marks, PW.[2018]

The combination of decitabine and idarubicin showed a synergistic effect in inducing cell death in various myeloid leukemia cell lines and primary AML cells, suggesting a more effective treatment strategy than decitabine alone.

This combination therapy not only inhibited tumor growth more effectively in mouse models but also triggered apoptosis and downregulated the Wnt/β-catenin pathway, which is linked to leukemia progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential combination of decitabine and idarubicin synergistically enhances anti-leukemia effect followed by demethylating Wnt pathway inhibitor promoters and downregulating Wnt pathway nuclear target. Li, K., Hu, C., Mei, C., et al.[2021]

In a study of 8 geriatric patients with acute myeloid leukemia, treatment with decitabine, with or without low-dose cytarabine, resulted in a 50% overall response rate, with 25% achieving complete remission and 25% achieving partial remission.

The treatment showed a median overall survival time of 9.5 months, with some patients surviving over a year, although it was associated with significant side effects, including severe myelosuppression in 87.5% of patients and pneumonia in 50%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical Efficacy of Decitabine Combined with or without Cytarabine-based Low Dose Regimen for Senile patients with Acute Myeloid Leukemia]. Zhou, HW., Zhou, MH., Wang, ZH., et al.[2019]

In a study of 19 children with high-risk, refractory, or relapsed acute myeloid leukemia (AML), treatment with decitabine combined with low dose chemotherapy resulted in a high response rate, with 15 achieving complete remission and only 1 not responding.

The treatment was found to be safe, with no treatment-related deaths, and led to a promising three-year overall survival rate of 79%, indicating it is an effective option for these challenging cases of pediatric AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy of decitabine combined with low dose chemotherapy on children with acute myeloid leukemia]. Fan, LY., Gao, L., Hu, DX., et al.[2023]

The D-CAG regimen, which combines decitabine with a modified chemotherapy approach, achieved a complete remission (CR) rate of 69.4% in 59 elderly patients (≥70 years) with newly diagnosed acute myeloid leukemia (AML), indicating its efficacy in this age group.

The treatment was found to be safe, with major adverse reactions including grade 3-4 myelosuppression and infections, but it significantly improved overall survival (OS) and event-free survival (EFS) for patients who achieved CR, with median OS of 19.8 months compared to 6.4 months for those who did not respond.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and Safety of Decitabine Combined with Modified CAG Regimen in Patients Aged ≥ 70 Years with Newly Diagnosed Acute Myeloid Leukemia]. Cao, L., Jiang, ZQ., Liu, WJ., et al.[2023]

Citations

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Phase II trial of 10-day ASTX727 (decitabine/cedazuridine ... In this prospective clinical trial, we investigate the efficacy of a novel 10-day induction regimen with fully oral combination therapy for pts with R/R AML.

2. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/2896/533121/Fully-Oral-Combination-of-Decitabine-Cedazuridine

Fully Oral Combination of Decitabine/Cedazuridine (ASTX727 ... The median follow-up time was 20 months. The ORR was 40/60 (67%), including 24 (40%) complete remission (CR), 13 (22%) CR with incomplete count ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38452788/

Oral decitabine and cedazuridine plus venetoclax for older or ... The primary outcome was overall response rate of ASTX727 plus venetoclax. Living patients who have not completed cycle one were not evaluable for response.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04817241

Testing Oral Decitabine and Cedazuridine (ASTX727) in ... This phase Ib/II trial studies the effects of ASTX727 (decitabine and cedazuridine) in combination with venetoclax in treating patients with higher-risk ...

5. cancertherapyadvisor.com cancertherapyadvisor.com/news/decitabine-cedazuridine-plus-venetoclax-under-review-for-aml/

Decitabine/Cedazuridine Plus Venetoclax Under Review ... The median overall survival was 15.5 months. The most common grade 3 or higher adverse events were febrile neutropenia, anemia, and neutropenia.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38316133/

Oral decitabine plus cedazuridine and venetoclax in ... We investigated the safety and activity of the first totally oral combination of decitabine plus cedazuridine and venetoclax in patients with higher-risk- ...

7. ashpublications.org ashpublications.org/ashclinicalnews/news/8640/Phase-II-Results-Point-Toward-a-New-Era-in

Phase II Results Point Toward a New Era in Treating Acute ... The trial documented grade 3 or greater treatment-​emergent adverse events in 98.0% of patients; these included febrile neutropenia (49.5%), ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.6504

An all-oral regimen of decitabine-cedazuridine (DEC-C) ... The 30- and 60-day mortality rates were 3.0% and 9.9%, respectively. PK data confirmed no drug-drug interactions between oral DEC-C and VEN.

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124056489

Fully Oral Combination of Decitabine/Cedazuridine ... 3 deaths occurred on study treatment in patients in remission and were potentially treatment-related (1 from bleeding and 2 from infections). Conclusions: ...