Oral Azacitidine for Acute Myeloid Leukemia

Not currently recruiting at 77 trial locations

Overseen By First line of the email MUST contain NCT # and Site #.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Bristol-Myers Squibb

Must not be taking: Hypomethylating agents

Disqualifiers: Acute promyelocytic leukemia, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how well a new oral medication, azacitidine, helps individuals with Acute Myeloid Leukemia (AML) who are in remission after chemotherapy. The goal is to determine if this treatment can prolong cancer-free periods compared to standard care alone. Participants will receive either oral azacitidine or a placebo (a pill with no active medication). Eligible participants must have been diagnosed with AML, undergone chemotherapy, and recently achieved remission. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that oral azacitidine is likely to be safe for humans?

Research has shown that oral azacitidine is generally well-tolerated by patients with acute myeloid leukemia (AML). In past studies, patients using oral azacitidine for ongoing treatment experienced positive safety outcomes. Most side effects were mild to moderate, such as nausea and diarrhea, which are common with many oral medications. Serious side effects occurred rarely.

Additionally, oral azacitidine has already received approval for other uses, indicating its general safety. This approval means it has been tested and used safely in various situations. While every medication carries some risks, data shows that oral azacitidine is usually safe for patients in remission from AML. Discussing possible side effects with a healthcare provider before joining a clinical trial is always important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for AML?

Oral Azacitidine is unique because it offers a new way to treat Acute Myeloid Leukemia (AML) with a convenient oral formulation, unlike the traditional intravenous chemotherapy treatments typically used. This delivery method means patients could potentially manage their treatment more easily at home, reducing the need for frequent hospital visits. Additionally, Azacitidine works by targeting abnormal cells and preventing their growth, which is a different approach compared to some current therapies focused mainly on killing cancer cells directly. Researchers are excited about this treatment as it could improve patient quality of life while offering an effective alternative to existing AML therapies.

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

Research has shown that oral azacitidine, which participants in this trial may receive, can benefit patients with Acute Myeloid Leukemia (AML). One study found that patients taking oral azacitidine lived longer overall and stayed in remission longer compared to those taking a placebo. Specifically, patients remained in remission for an average of 7.5 months, while those on a placebo stayed in remission for 3.7 months. Additionally, real-world data indicated that 12 months after starting oral azacitidine, 66.9% of patients had not relapsed, and 74.5% were still alive. These findings suggest that oral azacitidine holds promise for keeping older AML patients in remission. ^{1 2 5 6 7}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

This trial is for Japanese individuals aged 55 or older with Acute Myeloid Leukemia (AML) who are in complete remission after intensive chemotherapy. They must not have had prior bone marrow transplants, treatment with hypomethylating agents for MDS that led to AML within four months, or certain types of leukemia like acute promyelocytic leukemia.

Inclusion Criteria

I achieved complete remission from my cancer within 4 months after intensive chemotherapy.

I have been newly diagnosed with AML, either de novo or following MDS/CMML.

I am 55 years old or older.

Exclusion Criteria

I achieved complete remission after treatment with drugs that affect DNA.

I have acute leukemia or AML following a blood disorder, but not MDS or CMML.

I have had a bone marrow or stem cell transplant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral azacitidine plus best supportive care or placebo as maintenance therapy

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Oral Azacitidine
• Placebo

Trial Overview The study compares the effectiveness and safety of oral azacitidine plus best supportive care versus just best supportive care as maintenance therapy in patients who've achieved remission from AML following chemotherapy.

How Is the Trial Designed?

Group I: Oral Azacitidine Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Bristol-Myers Squibb

Lead Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Published Research Related to This Trial

Azacitidine, an antileukemia drug, has shown survival benefits in patients with high-risk myelodysplastic syndrome (MDS) and is effective in treating acute myelogenous leukemia (AML).

A pilot study with four subjects demonstrated that an oral formulation of azacitidine is bioavailable, with a mean bioavailability of 17.4% compared to subcutaneous administration, and was well-tolerated without severe toxicities, suggesting it warrants further investigation in phase 1 trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot pharmacokinetic study of oral azacitidine. Garcia-Manero, G., Stoltz, ML., Ward, MR., et al.[2023]

Oral azacitidine (Oral-AZA) has been approved for treating adult patients with acute myeloid leukemia (AML) in first complete remission, showing a significant median overall survival advantage of 9.9 months compared to placebo in the QUAZAR AML-001 trial.

Oral-AZA offers a more convenient dosing regimen than injectable azacitidine, allowing for extended treatment cycles, which may improve patient adherence and outcomes in maintenance therapy for AML and potentially in myelodysplastic syndromes (MDS).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral Azacitidine (CC-486) for the Treatment of Myeloid Malignancies. Garcia-Manero, G., Döhner, H., Wei, AH., et al.[2022]

In a study of 38 acute myeloid leukemia (AML) patients treated with azacitidine, the median overall survival was approximately 10 months for both newly diagnosed and relapsed patients, indicating its efficacy as a treatment option for those unfit for intensive chemotherapy.

The treatment showed a 29% positive effect on reducing transfusion dependency, which was linked to better survival outcomes, highlighting the potential benefits of azacitidine in managing symptoms and improving quality of life for AML patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Azacitidine in De Novo and Relapsed Acute Myeloid Leukemia: A Retrospective Comparative Study. Gemuenden, C., Benz, R., Senn, O., et al.[2015]

Oral azacitidine significantly improves overall survival in patients with acute myeloid leukaemia (AML) after induction therapy, with a median survival gain of 9.9 months compared to placebo, as shown in the QUAZAR AML-001 trial involving a substantial number of participants.

The cost-effectiveness analysis indicated that oral azacitidine has a probabilistic incremental cost-effectiveness ratio (ICER) of approximately £32,480 per quality-adjusted life year (QALY) gained compared to watch-and-wait plus best supportive care, making it a recommended option for maintenance treatment in eligible AML patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral Azacitidine for Maintenance Treatment of Acute Myeloid Leukaemia After Induction Therapy: An Evidence Review Group Perspective of a NICE Single Technology Appraisal. Witlox, W., Grimm, S., Howick, J., et al.[2023]

The Vidaza Access Program in Belgium successfully facilitated access to azacitidine treatment for 175 patients with myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and chronic myelomonocytic leukemia (CMML) by streamlining the approval process for patient dossiers.

Out of the 175 patient dossiers submitted, 163 were approved by Celgene, demonstrating the program's effectiveness in ensuring timely treatment initiation without financial risk to hospitals, which is crucial for patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azacitidine access program for Belgian patients with myelodysplastic syndromes, acute myeloid leukemia or chronic myelomonocytic leukemia. Meers, S., Selleslag, D., Potier, H., et al.[2018]

Azacitidine is an effective and well-tolerated treatment for patients with higher-risk myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML), including older patients who are ineligible for stem cell transplants, as demonstrated in pivotal phase 3 trials.

It is the only approved hypomethylating agent that has been shown to prolong overall survival compared to conventional care, making it the recommended first-line treatment for most patients with higher-risk MDS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azacitidine: A Review in Myelodysplastic Syndromes and Acute Myeloid Leukaemia. Scott, LJ.[2022]

The maximum-tolerated dose (MTD) of oral azacitidine was determined to be 480 mg, with common side effects including diarrhea, nausea, and febrile neutropenia, indicating a manageable safety profile for patients with myelodysplastic syndromes (MDSs), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML).

Oral azacitidine showed significant clinical activity, achieving a 35% overall response rate in previously treated patients and a 73% response rate in previously untreated patients, demonstrating its efficacy in reducing DNA methylation and improving hematologic responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of oral azacitidine in myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia. Garcia-Manero, G., Gore, SD., Cogle, C., et al.[2022]

In the AZA-001 trial, azacitidine significantly improved survival in patients with high-risk myelodysplastic syndrome and acute myeloid leukemia, with 91 out of 179 patients responding to treatment after a median of 14 cycles.

Continued treatment with azacitidine beyond the first response led to an improved response category in 48% of patients, suggesting that ongoing therapy can enhance clinical benefits for those who initially respond.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continued azacitidine therapy beyond time of first response improves quality of response in patients with higher-risk myelodysplastic syndromes. Silverman, LR., Fenaux, P., Mufti, GJ., et al.[2022]

In a real-life study of 49 patients with myelodysplastic syndrome (MDS), acute myeloid leukaemia (AML), and chronic myelomonocytic leukaemia (CMML), azacitidine demonstrated a clinically acceptable safety profile, with 67.3% of patients experiencing treatment-related adverse events.

Efficacy results showed that 41.4% of MDS and CMML patients achieved a complete or partial response, and 43.8% of transfusion-dependent patients became transfusion-independent, with a median overall survival of 490 days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of azacitidine in Belgian patients with high-risk myelodysplastic syndromes, acute myeloid leukaemia, or chronic myelomonocytic leukaemia: results of a real-life, non-interventional post-marketing survey. Beguin, Y., Selleslag, D., Meers, S., et al.[2015]

In a study of 149 patients with higher-risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML), azacitidine treatment resulted in a median progression-free survival (PFS) of 10.9 months and an overall survival (OS) of 14.1 months, demonstrating its effectiveness in a real-world clinical setting.

The safety profile of azacitidine was consistent with previous clinical trials, and factors such as Eastern Cooperative Oncology Group (ECOG) performance status and red blood cell transfusion prior to treatment were identified as predictive factors for better PFS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of performance status and transfusion dependency on outcome of patients with myelodysplastic syndrome, acute myeloid leukemia and chronic myelomonocytic leukemia treated with azacitidine (PIAZA study). Wehmeyer, J., Zaiss, M., Losem, C., et al.[2019]

Citations

1. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/2425/531542/Real-World-Treatment-Patterns-and-Outcomes-with

Real-World Treatment Patterns and Outcomes with Oral ... At 12 mo, estimated OS and rwRFS rates from Oral-AZA initiation were 88.2% (standard error [SE], 2.3) and 85.5% (SE, 2.5), respectively. Median ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40233158/

Real-world treatment patterns and outcomes with oral ... Rates of real-world relapse-free survival and overall survival at 12 months from oral-AZA initiation were 66.9% and 74.5%, respectively. During ...

3. onuregpro.com onuregpro.com/efficacy

ONUREG® (azacitidine) Efficacy Profile | for HCPs Median overall survival was ~4 years in patients with an NPM1 mutation treated with ONUREG ... Analysis limitations: Results should be interpreted with caution, ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa2004444

Oral Azacitidine Maintenance Therapy for Acute Myeloid ... CC-486 maintenance therapy was associated with significantly longer overall and relapse-free survival than placebo among older patients with AML ...

5. healthtree.org healthtree.org/aml/community/articles/outcomes-oral-azacitidine-secondary-aml

Outcomes from Oral Azacitidine Maintenance Therapy AML-MRC patients who took oral azacitidine had a longer time in remission of 7.5 months, compared to the placebo group's 3.7 months. In ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01757535

Study Details | NCT01757535 | Efficacy of Oral Azacitidine ... Survival outcomes with oral azacitidine maintenance in patients with acute myeloid leukemia in remission by receipt of initial chemotherapy: subgroup ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124051784

Real-World Treatment Patterns and Outcomes with Oral ... Oral-AZA maintenance therapy significantly prolonged overall survival (OS) and relapse-free survival (RFS) compared with placebo for patients (pts) with acute ...