Oral Azacitidine for Acute Myeloid Leukemia

Recruiting at 72 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

19 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to assess the efficacy and safety of oral azacitidine plus best supportive care versus best supportive care as maintenance therapy in a cohort of Japanese participants ≥ 55 years of age with Acute Myeloid Leukemia (AML) and in complete remission/complete remission with incomplete blood count recovery after conventional induction chemotherapy with or without consolidation chemotherapy.

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.

What data supports the effectiveness of the drug oral azacitidine for treating acute myeloid leukemia?

Research shows that oral azacitidine significantly improved overall survival in patients with acute myeloid leukemia, with a median survival gain of 9.9 months compared to a placebo. Additionally, azacitidine has been effective in improving survival in patients with related conditions like myelodysplastic syndromes. ^{1 2 3 4 5}

Is oral azacitidine safe for humans?

Oral azacitidine has been studied for safety in patients with conditions like myelodysplastic syndromes and acute myeloid leukemia. It is generally well-tolerated, meaning most people can take it without serious side effects, although individual experiences may vary. ^{3 5 6 7 8}

How is oral azacitidine different from other drugs for acute myeloid leukemia?

Oral azacitidine is unique because it is taken by mouth, unlike the traditional injectable form, making it more convenient for patients. It allows for extended dosing over 14 days in a 28-day cycle, which is not feasible with injections, and has shown a significant survival benefit in patients with acute myeloid leukemia in remission. ^{1 2 5 9 10}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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]

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]

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]

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]

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]

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, 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]

References

1. New Zealand 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. [2023]

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

Continued azacitidine therapy beyond time of first response improves quality of response in patients with higher-risk myelodysplastic syndromes. [2022]

3. England 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). [2019]

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

Efficacy of Azacitidine in De Novo and Relapsed Acute Myeloid Leukemia: A Retrospective Comparative Study. [2015]

5. New Zealand pubmed.ncbi.nlm.nih.gov

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

6. England 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. [2015]

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

Phase I study of oral azacitidine in myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Azacitidine access program for Belgian patients with myelodysplastic syndromes, acute myeloid leukemia or chronic myelomonocytic leukemia. [2018]

9. England pubmed.ncbi.nlm.nih.gov

A pilot pharmacokinetic study of oral azacitidine. [2023]

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

Oral Azacitidine (CC-486) for the Treatment of Myeloid Malignancies. [2022]